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pubmed_977_4860 | BACKGROUND
SARS-CoV-2 vaccination is strongly recommended in kidney transplant recipients (KTR) and dialysis patients. Whether these vaccinations may trigger alloantibodies, is still debated.
METHODS
In the current study we evaluated the effect of SARS-CoV-2 mRNA vaccines on anti-Human Leukocyte Antigen (HLA) and 60 anti-non-HLA antibody profiles in clinically stable KTR and dialysis patients. In total, we included 28 KTR, 30 patients on haemodialysis, 25 patients on peritoneal dialysis and 31 controls with a positive seroresponse 16-21 days after the first dose of either the SARS-CoV-2 mRNA BNT162b2 or mRNA-1273 vaccine. Both anti-HLA and anti-non-HLA antibodies were determined prior to vaccination and 21 to 35 days after the second vaccine dose.
RESULTS
Overall, the proportion of patients with detectable anti-HLA antibodies was similar before and after vaccination (class I 14% vs. 16%, p = 0.48; class II 25% before and after vaccination). After vaccination, there was no pattern in 1) additionally detected anti-HLA antibodies, or 2) the levels of pre-existing ones. Additional anti-non-HLA antibodies were detected in 30% of the patients, ranging from 1 to 5 new anti-non-HLA antibodies per patient. However, the clinical significance of anti-non-HLA antibodies is still a matter of debate. To date, only a significant association has been found for anti-non-HLA ARHGDIB antibodies and long-term kidney graft loss. No additionally developed anti-ARHGDIB antibodies or elevated level of existing anti-ARHGDIB antibodies was observed.
CONCLUSION
The current data indicate that SARS-CoV-2 mRNA vaccination does not induce anti-HLA or anti-non-HLA antibodies, corroborating the importance of vaccinating KTR and dialysis patients. | 10.1016/j.trim.2022.101670 |
pubmed_1042_11492 | This study assessed in depth the use of first- and second-generation antipsychotic (FGAP/SGAP) drugs in France. A 1/97th random sample of beneficiaries affiliated to the French Health Insurance system-Echantillon Généraliste des Bénéficiaires (EGB)-was used: (i) 621 662 persons in 2015 among which 11 319 had an antipsychotic (AP) prescription; (ii) a sample of first AP prescriptions concerning 5 935 patients in 2013 and 2014 (no AP in the last 6 months of 2012) for whom diagnosis was available in 40% of cases. In 2015, AP prevalence was 21.9/1 000. SGAP/FGAP ratio was 1.02. Long-lasting prescriptions were rare: 1.79/1 000 for FGAP and 1.38/1 000 for SGAP. FGAP first prescriptions were higher than SGAP for each age class, except for <18 aged patients; 2.85% had both generations; 50.7% of the patients had another psychotropic. GPs prescribed more FGAPs than SGAPs, psychiatrists prescribed more SGAPs and hospital-based practitioners prescribed both generations equally, and these patterns changed across age ranges: For the elderly, GPs are the more frequent prescribers. SGAP/FGAP ratio is different by diagnostic categories. In France, FGAPs are largely prescribed by GPs mainly for the elderly, but young and adult patients are concerned as well. Inappropriate antipsychotic consumption through off-label use, which adds to the co-prescription, especially in vulnerable population groups, mainly concerns FGAP prescriptions by GPs who do not have psychiatric training and limited contact with psychiatrists. Attention should then be brought to the regulatory advisory agencies in order to better inform and train the prescribers. | 10.1111/fcp.12553 |
pubmed_536_17814 | This brief review was written with the intention of familiarizing the reader with autonomic peripheral neuropathies. We have discussed what we think are the main presenting symptoms of these conditions, briefly outlining some specific autonomic neuropathies. We then provide a general guideline to evaluation and diagnosis by using both widely available, as well as more sophisticated, techniques. Finally, we have addressed management. Whenever possible, specific treatment of underlying disorders leads to the best outcome However, for many autonomic neuropathies, no cure is available, although symptomatic management can effectively improve patients" quality of life. | pubmed_536_17814 |
pubmed_534_10123 | Variation in terrestrial mammalian skull morphology is known to constrain feeding performance, which in turn influences dietary habits and ultimately fitness. Among mustelids, otters have evolved two feeding specializations: underwater raptorial capture of prey (mouth-oriented) and capture of prey by hand (hand-oriented), both of which have likely associations with morphology and bite performance. However, feeding biomechanics and performance data for otters are sparse. The first goal of this study was to investigate the relationships between feeding morphology and bite performance among two mouth-oriented piscivores (Pteronura brasiliensis and Lontra canadensis) and two hand-oriented invertebrate specialists (Enhydra lutris and Aonyx cinerea). Since other vertebrate taxa that are mouth-oriented piscivores tend to possess longer skulls and mandibles, with jaws designed for increased velocity at the expense of biting capability, we hypothesized that mouth-oriented otters would also possess long, narrow skulls indicative of high velocity jaws. Conversely, hand-oriented otters were expected to possess short, blunt skulls with adaptations to increase bite force and crushing capability. Concomitant with these skull shapes we hypothesized that sea otters would possess a greater mandibular bluntness index, providing for a greater mechanical advantage compared to other otter species investigated. A second goal was to examine morphological variation at a finer scale by assessing variation in cranial morphology among three sea otter subspecies. Since diet varies among these subspecies, and their populations are isolated, we hypothesized that the magnitude of mandibular bluntness and concomitant mechanical advantage, as well as occlusal surface area would also vary within species according to their primary food source (fish versus hard invertebrates). Functional expectations were met for comparisons among and within species. Among species the phylogeny suggests a deeply rooted transition to alternative foraging types. Yet within foraging types alternative species were also strongly variable, suggesting either selective differences in the extent or nature of realized foraging mode, or an accumulation of non-adaptive changes during the long independent evolutionary history. At the finest scale, variation among subspecies indicates that trophic adaptation occurred rapidly, making it interesting that we happened to find both deeply and shallowly-rooted transformations associated with diet type in otter species and subspecies. | 10.1371/journal.pone.0143236 |
pubmed_183_1819 | OBJECTIVE
To examine the effects of a 30 min, 1 Hz subthreshold rTMS in a case of cortical tremor which is caused by hyperexcitability of sensorimotor cortex.
METHODS
Stimulation was applied over primary and, in a second time, over premotor cortex (M1 and PMC, respectively). Tremor was monitored by accelerometers placed on the index fingers of hands outstretched, before and several times after rTMS. Each rTMS session consisted of 1800 pulses delivered at 1 Hz with an intensity of 90% of resting motor threshold.
RESULTS
PMC but not M1 stimulation led to a decrease of the postural tremor (90% decrease of acceleration total spectral power). This functional benefit was associated to normalization of electrophysiologic parameters (short-interval intracortical inhibition and cortical silent period duration). Moreover, when stimulating PMC during two daily sessions, improvement of the tremor was longer than one day stimulation and this benefit was associated with functional improvement.
CONCLUSIONS
This study shows that 1 Hz rTMS over premotor cortex can improve cortical tremor.
SIGNIFICANCE
These results raise the interest of the motor cortical stimulation as a possible therapeutic target for treatment of action tremor. | 10.1016/j.clinph.2007.04.014 |
pubmed_317_18450 | A 37-year-old man with moderately severe hemophilia A (factor VIII of 1.2%), who had a normal liver without liver cirrhosis or hepatocellular carcinoma, was referred to our liver transplantation (LT) team. LT was planned for sufficient coagulation factor level maintenance and prophylaxis against future hemorrhagic complications. The donor was the patient's 35-year-old wife, who was nonhemophilic. We performed an auxiliary partial orthotopic liver transplantation (APOLT) with the approval of the Institutional Ethics Committee. A left partial liver graft taken from the donor was orthotopically transplanted to the recipient after resection of the native left hemiliver while preserving the native right lobe. After surgery, the patient tolerated the procedure, and tacrolimus was used to maintained immunosuppression. In this recipient, factor VIII activity significantly increased soon after the APOLT, and has been maintained at >20% without any further bleeding episodes for the past 74 months since the procedure. This finding suggests that APOLT may be an effective alternative treatment for patients with hemophilia A. | pubmed_317_18450 |
pubmed_885_10390 | Radiation dosimetry of highly modulated dose distributions requires a detector with a high spatial resolution. Liquid filled ionization chambers (LICs) have the potential to become a valuable tool for the characterization of such radiation fields. However, the effect of an increased recombination of the charge carriers, as compared to using air as the sensitive medium has to be corrected for. Due to the presence of initial recombination in LICs, the correction for general recombination losses is more complicated than for air-filled ionization chambers. In the present work, recently published experimental methods for general recombination correction for LICs are compared and investigated for both pulsed and continuous beams. The experimental methods are all based on one of two approaches: either measurements at two different dose rates (two-dose-rate methods), or measurements at three different LIC polarizing voltages (three-voltage methods). In a comparison with the two-dose-rate methods, the three-voltage methods fail to achieve accurate corrections in several instances, predominantly at low polarizing voltages and dose rates. However, for continuous beams in the range of polarizing voltages recommended by the manufacturer of the LICs used, the agreement between the different methods is generally within the experimental uncertainties. For pulsed beams, the agreement between the methods is poor. The inaccuracies found in the results from the three-voltage methods are associated with numerical difficulties in solving the resulting equation systems, which also make these methods sensitive to small variations in the experimental data. These issues are more pronounced for the case of pulsed beams. Furthermore, the results suggest that the theoretical modelling of initial recombination used in the three-voltage methods may be a contributing factor to the deviating results observed. | 10.1088/0031-9155/57/21/7161 |
pubmed_180_3172 | The effect of hypochlorite treatment on the layer thickness and conductivity of a state-of-the-art high conducting poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) is investigated as a function of exposure time and hypochlorite concentration. Because of overoxidation by the hypochlorite the PEDOT:PSS conductivity is decreased by 10 orders of magnitude. Comparison of thickness and conductivity as a function of time shows that a residual insulating layer remains on the substrate upon treatment. Going from a low (<0.01%) to a high (>0.1%) hypochlorite concentration the interaction between PEDOT:PSS and hypochlorite changes from reaction- to diffusion limited. The decrease in conductivity can be interpreted in terms of the interruption of percolating conductive pathways by the reaction between PEDOT and hypochlorite. | 10.1021/jp4050836 |
pubmed_1105_9569 | Oligoribonucleases are essential components of RNA and DNA metabolism and close homologues of genes encoding them are found not only in prokaryotes but also in a wide range of eukaryotes, including yeast and humans. Inactivation of the oligoribonuclease gene (orn) can result in cellular lethality. Despite their important biological function, they have been studied little from a structural point of view. In this report, the cloning, expression, crystallization and preliminary X-ray analysis of XC847, a DEDDh-type 3'-5' oligoribonuclease from the plant pathogen Xanthomonas campestris pv. campestris, a Gram-negative bacterium causing major worldwide disease of cruciferous crops, is described. The XC847 crystals diffracted to a resolution of at least 2.1 A. They are tetragonal and belong to space group P4(3)2(1)2, with unit-cell parameters a = b = 67.5, c = 89.8 A. One molecule is present per asymmetric unit. | 10.1107/S1744309105027132 |
pubmed_900_15251 | We hypothesized local recurrence of Grade 1 chondrosarcoma in the long bones of the extremity negatively influences survival. To explore that notion, we retrospectively reviewed 164 patients treated surgically for Grade 1 chondrosarcoma of the long bones. Local recurrence occurred in 21 (13%) patients. Four patients had progression of tumor grade on recurrence, and six patients had more than one local recurrence. Seven of the 21 patients with local recurrences had metastasis. Six of the 21 patients with local recurrences died secondary to chondrosarcoma. Local recurrence, progression of grade at recurrence, and distant metastases all were associated with a decrease in overall survival. The difference in survival was not apparent until after 5 years and was more pronounced after 10 years. Recurrence may be regarded as a declaration of an aggressive phenotype and should be treated as such. | 10.1097/BLO.0b013e3180caac2c |
pubmed_302_20156 | Gene targeting ('knock-out') technology is now widely used in the basic science of all disciplines of pathology and particularly auto-immune and inflammatory disease. Gene targeting is the wilful introduction of precise mutations into the genome of an animal, usually a mouse, affecting the function of a single gene or genes. The phenotyping of knockout mice provides whole animal data on the functions of individual genes in pathophysiological settings, and frequently provides the basis for novel therapeutic strategies. 'Knock-ins', the Cre-LoxP system and conditional knockouts are important new advances. This paper serves as an introduction to the methodology and draws on examples of major advances in inflammation research provided by the targeting of cytokines, in particular the tumour necrosis factor family of ligands. | 10.1080/003130201201111230 |
pubmed_68_14163 | This paper describes a digital image processor for ultrasonic speckle suppression that was explicitly designed to satisfy the requirements of detail preservation, adequate smoothing and real-time operation. The first two of these requirements were addressed by selecting a nonlinear adaptive algorithm, which uses a measure of local homogeneity to adjust the amount of smoothing performed at each point of the scan, and employing a large (9 x 9 pixels) filtering window. Real-time operation was achieved by developing a highly concurrent systolic architecture that allowed the efficient mapping of the algorithm into low-cost high-density hardware. Initial experience, obtained by interfacing the processor to a scanner, suggests that this type of processing is capable of enhancing the visibility of subtle differences in echogenicity while retaining genuine image detail, as judged by the preservation of the small vessels and ducts. In addition to its impact on contrast resolution, this form of real-time speckle suppression should also prove valuable as a preprocessing stage before performing other digital image processing operations that are sensitive to noise, such as segmentation and three-dimensional rendering. | 10.1016/0301-5629(94)90064-7 |
pubmed_788_19323 | BACKGROUND
This paper examines the prevalence of psychotropic substance (tobacco, alcohol, narcotic drugs) use among inmates of Lithuanian prisons and the association between drug use and psychosocial factors.
MATERIAL/METHODS
The questionnaire used was based on the ESPAD questionnaire, modified to fit the specific respondent group. At the time of the study there were 9634 inmates in Lithuanian penal institutions; 1304 of them participated in the study, 67 (5.2%) were women, 115 (8.8%) boy minors, and 1122 (86%) men. Statistical analysis was carried out using EpilInfo 6.04.
RESULTS
It was revealed that 48.7% of the prisoners had used drugs at least once in their lives, 13.8% of prisoners currently used narcotic drugs, and 39.8% had first used illicit (narcotic) drugs in prison. 85.3% currently smoked tobacco and 92.1% had drunk alcohol at least once in their lives.
CONCLUSIONS
Psychotropic substances are often used due to their psychological impact. Imprisoned people constitute a high-risk group of drug users and distributors of narcotic drugs. Consequently, the problem of psychotropic substance addiction in penal institutions awakens more concern than the same problem in the general society. Intravenous narcotic drugs stimulating dangerous behavior are prevalent in Lithuanian prisons. | pubmed_788_19323 |
pubmed_759_4817 | Goldfish performed a simple left-right discrimination in a Y-maze under the influence of amphetamine. The subjects showed facilitation of learning at a low dose (1.25 mg/l) but not at 2.0 mg/l. | 10.1007/BF00492372 |
pubmed_1076_1814 | Two hydrogen-producing bacterial strains were newly isolated and identified as Enterobacter sp. Z-16 and Clostridium sp. C-32 by 16S rDNA sequence analysis. Various parameters for hydrogen production, including substrates, initial pH and temperature, have been studied. The optimum condition for hydrogen production of strain Z-16 were achieved as: initial pH7.0, temperature 35 degrees C , sucrose as the favorite substrate. In comparison, The optimum condition for hydrogen production of strain C-32 were obtained as: initial pH8.0, temperature 35 degrees C , maltose as the favorite substrate . Under batch fermentative hydrogen production conditions, the maximal hydrogen conversion rate for strain Z-16 and strain C-32 were 2.68 mol H2/mol sucrose and 2.71mol H2/mol maltose, respectively. Using glucose as substrate, the hydrogen conversion rate of strain Z-16 and strain C-32 were 2.35 and 2.48 mol H2/mol glucose, respectively. This research suggest a good application potential of strain Z-16 and C-32 in the future biological hydrogen production. | pubmed_1076_1814 |
pubmed_427_2426 | Direct arterial pressure, heart rate, and ECG have been recorded over a 24-hour period in nine individuals who were completely unrestricted throughout the study. Forty-nine separate cigarette smoking episodes were clearly indicated and analyzed. The results of our study confirm a significant increase in arterial pressure five minutes after smoking a cigarette. The systolic rise in pressure (mean 10.7 mm. Hg, P less than 0.001) was approximately twice that of the diastolic rise (5.3 mm. Hg, P less than 0.001) and was present under different conditions of everyday life with notable exception of lying in bed before sleep, We found no quantitative difference between normotensive and hypertensive subjects. There was no certain change in heart rate (mean increase +0.8 beats per minute, t equals 0.59, NS) in the group as a whole. Smoking also had a short-term action consisting of a brief fall in arterial pressure and heart rate occuring over eight to ten heart beats following immediately after the first inhalation of tobacco smoke, followed by a rebound rise in arterial pressure to a level greater than the presmoking level; this is probably a vagal effect. Cigarette smoking caused angina pectoris in one individual and the records showed ST-segment depression in the ECG before the subjective appreciation of pain. | 10.1016/0002-8703(75)90004-6 |
pubmed_146_21864 | Childhood obesity is a strong risk factor for associated comorbidities such as type 2 diabetes, cardiovascular disease, and orthopedic abnormalities in youth and its increasing incidents thus represents a major public health concern. The following review provides evidence for a familial association between parental and child weight status, eating behaviors, and food preferences. It further draws the link between environmental influences, such as parent feeding practices, and the development of child eating behaviors and thereby elucidates how genetic and nongenetic influences can contribute to the familial transmission of obesity. We use eating in the absence of hunger, an eating trait which refers to children's susceptibility to eating in response to the presence of palatable foods in the absence of hunger, as an example to illustrate these associations. The review concludes with an outlook on possibilities for future research efforts in the field. | 10.1093/jpepsy/jsn037 |
pubmed_594_5198 | As part of NOAA's National Status and Trends Mussel Watch Program, oysters were sampled along the Gulf of Mexico coast each winter from 1986 to 1993 (The present analysis deals with 1986-1993 Mussel Watch data; the Mussel Watch project itself continues at this printing) and analyzed for trace metal, polynuclear aromatic hydrocarbons and pesticide body burden, plus a series of biological variables designed to assess population status and health. We identified contaminant and biological variables in which large-scale spatial processes played an important role in establishing population values by examining the likelihood that neighboring bays tended to have populations with body burdens or population attributes more similar than expected by chance. Local or watershed-dependent factors, such as land use and freshwater inflow, are important in controlling the bay-to-bay variation in body burden in most contaminants. However, the bay-to-bay variations in body burden of some metals (As, Cd, Hg, Ni, Se) appear to be principally influenced by larger-scale climatic factors. These metals and the biological variable shell length demonstrated a strong degree of similarity between bays over a large regional area reminiscent of the pattern shown by climatic factors, such as temperature and precipitation. In contrast, among the organics, none of the PAHs showed even a moderately strong climatic signal. Among the pesticides, only two did (dieldrin, total DDTs). These pesticides and the biological variables, reproductive stage and Perkinsus marinus prevalence and infection intensity, had spatial patterns that suggested both a local and a regional influence to their geographic distributions. This same pattern is exhibited by freshwater runoff. Metal contaminants also behaved distinctively compared to organics in the temporal influence of climate in establishing the interannual variability in body burden. For the organics, trends in interannual variability were strongly influenced by climate, whereas spatial trends were not. In contrast, most metals were unaffected by climatic forcing both spatially and temporally. However, all of the metals having a spatial pattern strongly influenced by climate (As, Cd, Hg, Ni, Se) also exhibited interannual variations related to variations in climate. | 10.1007/s002440010218 |
pubmed_531_5896 | Long-term effective use of clophelin was observed only in 1/3 of pregnant suffering of hypertensive disease. The efficacy of treatment with this drug is determined not so much by its hypotensive action as by its influence on the state of the central hemodynamics. Clophelin may often reduce the minute cardiac volume and thus, deteriorate the uterine-placental blood flow and that is why its use be carried out under meticulous control of the central circulation. The authors designed a mathematical model for the prognosis of the efficiency of long-term clophelin treatment in pregnant women with hypertensive disease. | pubmed_531_5896 |
pubmed_721_8062 | A survey of Angiostrongylus cantonensis was carried out to investigate the mode of transmission from mollusc to rat in a fixed study area of Yoron Island from 1979 to 1982. Rattus rattus was found to be infected with a small number of worms in spite of heavy infection with third-stage larvae in Achatina fulica and an abundance of this snail in the area. Natural infection and/or susceptibility with A. cantonensis were confirmed in three small snail species. Bradybaena circulus, Fruticicola despecta and Luchuena reticulata. Young A. fulica was found to be infected with fewer third-stage larvae than mature A. fulica. It was concluded that molluscs which were infected with a small number of third-stage larvae of A. cantonensis play an important role in maintaining the life cycle of A. cantonensis. The percentage of rat stomachs containing mollusc tissue was relatively low, and the incidence and infection was low in rats. Infection with A. cantonensis did not occur very often in R. rattus in nature. | 10.1017/s0022149x00010099 |
pubmed_1012_20905 | In mouse pancreatic insulin-producing betaTC cells, oxidative stress due to H(2)O(2) causes tyrosine phosphorylation in various proteins. To identify proteins bearing phosphotyrosine under stress, the proteins were affinity purified using an anti-phosphotyrosine antibody-conjugated agarose column. A protein of 180kDa was identified as clathrin heavy chain (CHC) by electrophoresis and mass spectrometry. Immunoprecipitated CHC showed tyrosine phosphorylation upon H(2)O(2) treatment and the phosphorylation was suppressed by the Src kinase inhibitor, PP2. The phosphorylation status of CHC affected the intracellular localization of CHC and the clathrin-dependent endocytosis of transferrin under oxidative stress. In conclusion, CHC is a protein that is phosphorylated at tyrosine by H(2)O(2) and this phosphorylation status is implicated in the intracellular localization and functions of CHC under oxidative stress. The present study demonstrates that oxidative stress affects intracellular vesicular trafficking via the alteration of clathrin-dependent vesicular trafficking. | 10.1016/s0006-291x(02)02195-2 |
pubmed_49_3393 | 74 cases of spontaneous subarachnoid hemorrhage (SAH) were followed up for a period of 1 to 7 years, most of them had been examined by CT-scan and/or cerebral angiography. The life-table method was used to determine the cumulative survival rate and cumulative recurrence rate. The mortality rates in both acute and chronic stages and the re-bleeding rate were found to be essentially similar to those of other series of SAH admitted to a tertiary care center as were reported in the Chinese and world literature. Hypertension was probably a risk factor for SAH. The incidence of diabetes mellitus in the present series was significantly higher than that found in the same age groups of general population in Shanghai, which fact deserves further evaluation. The clinical characteristics of the patients in the acute stage were not found to be related to their outcome. | pubmed_49_3393 |
pubmed_364_3375 | Real-time label-free techniques are used to profile G protein-coupled receptor (GPCR) signaling pathways in living cells. However, interpreting the label-free signal responses is challenging, and previously reported methods do not reliably separate pathways from each other. In this study, a continuous angular-scanning surface plasmon resonance (SPR) technique is utilized for measuring label-free GPCR signal profiles. We show how the continuous angular-scanning ability, measuring up to nine real-time label-free parameters simultaneously, results in more information-rich label-free signal profiles for different GPCR pathways, providing a more accurate pathway separation. For this, we measured real-time full-angular SPR response curves for Gs, Gq, and Gi signaling pathways in living cells. By selecting two of the most prominent label-free parameters: the full SPR curve angular and intensity shifts, we present how this analysis approach can separate each of the three signaling pathways in a straightforward single-step analysis setup, without concurrent use of signal inhibitors or other response modulating compounds. | 10.1021/acs.analchem.0c02652 |
pubmed_350_5815 | We have shown previously that proteoliposomes reconstituted with purified Na+K+-ATPase from Ehrlich ascites tumor cells, transport Na+ with low efficiency (Spector, M., O'Neal, S. and Racker, E. (1980) J. Biol. Chem., 255, 5504-5507). We now present evidence that this low efficiency (expressed in the ratio of Na+-transported/ATP-hydrolyzed) is caused by the phosphorylation of the beta subunit of the Na+K+-ATPase by an endogenous protein kinase. On addition of [gamma-32P]ATP, crude tumor plasma membrane preparations phosphorylated the beta subunit of the ATPase, whereas crude mouse brain plasma membranes did not. However, solubilized Na+K+-ATPase from either tumor or brain wre phosphorylated by purified protein kinase from the tumor plasma membrane and dephosphorylated by a phosphatase. In both cases, the phosphorylated enzyme was inefficient; the dephosphorylated enzyme was efficient after reconstitution into liposomes. During isolation of the Na+K+-ATPase from Ehrlich ascites tumor or mouse brain, an endogenous protease partially cleaved from the beta subunit a polypeptide of 29,000 daltons that contained the phosphorylation site. The proteolytic cleavage of the beta subunit was partially inhibited by phenylmethylsulfonyl fluoride and the major site of phosphorylation was then seen in the 53,000-dalton beta subunit of the enzyme. The isolated 29,000-dalton polypeptide from mouse brain ATPase was phosphorylated by tumor protein kinase with a stoichiometry of 1 mol of phosphate/mol of protein. When this 29,000-dalton polypeptide from mouse brain was incorporated into the tumor Na+K+-ATPase after mild proteolytic digestion, a marked increase in efficiency was observed after reconstitution of the Na+ pump. | pubmed_350_5815 |
pubmed_1092_504 | Cytomegalovirus (CMV) has been associated with autoimmune diseases, but linking this common virus to disease pathology has been difficult. In this issue of Cell Host & Microbe, Liu et al. (2016) identify a CMV-cross-reactive autoantibody that also recognizes CIP2A on natural killer cells, possibly affecting their function in autoimmune patients. | pubmed_1092_504 |
pubmed_61_10646 | OBJECTIVE
To investigate if nitric oxide (NO) derived from inducible NO synthase (iNOS) regulates apoptosis and/or cell shedding in uroepithelial cells in vivo and in vitro, as bladder epithelial cells undergo shedding during urinary tract infection, which is considered a part of the host's defence and is thought to take place via an apoptotic pathway.
MATERIALS AND METHODS
Bladders and kidneys of mice infected with Escherichia coli were used to study caspase-3 immunoreactivity at different times after infection. Wild-type (E. coli 1177) and type-1 recombinant (E. coli PKL4) bacteria were used. iNOS-deficient mice were used to study the association of caspase-3 with iNOS. Isolated human uroepithelial cells were used to examine the effect of the NO donor DETA/NO and the peroxynitrite generator SIN-1 on caspase-3 activity and cell shedding in vitro.
RESULTS
Many caspase-3 immunoreactive neutrophils were found soon after infection and some superficial bladder epithelial cells were also immunoreactive for caspase-3.
CONCLUSIONS
Caspase-3 immunoreactivity was also detected in neutrophils and bladder epithelial cells of infected iNOS-deficient mice. There was no co-expression between iNOS- and caspase-3 in bladder epithelial cells. DETA/NO and SIN-1 did not stimulate caspase-3 activity or cell shedding in isolated human uroepithelial cells. Caspase-3 and iNOS are not co-expressed in uroepithelial cells and apoptosis is evident in the absence of iNOS. Exogenous NO did not induce apoptosis or cell shedding in isolated human uroepithelial cells. | 10.1111/j.1464-410X.2006.06151.x |
pubmed_279_12732 | The purpose of this study was to monitor selected aspects of the three-dimensional kinematics of the knee during walking with regular shoes and with modified shoes that induced either pronation or supination of the foot. Steinmann traction pins were inserted into the right tibia and femur of five adult men who had apparently normal lower extremities. Target clusters mounted onto the pins were filmed by four cine cameras operating at 100 frames/sec. Two trials per subject were analyzed for each of the three experimental conditions: regular running shoes, running shoes with a 10 degree valgus wedge, and running shoes with a 10 degree varus wedge. The different types of footwear induced only minor kinematic changes at the knee during the stance phase of walking. The angular patterns of the tibiofemoral joint were modified by less than 1 degree, whereas the translatory patterns were altered by 2 mm. Immediately following foot-strike, the valgus-wedge shoes caused the tibia to rotate internally 4 degrees more than the varus-wedge shoes, but at the tibiofemoral joint no consistent differences in the pattern of internal-external rotation between normal and modified footwear were measureable. These findings suggest that, in the healthy lower extremity, increased internal and external tibial rotation is resolved at the hip joint, with changes at the tibiofemoral joint that barely are detectable with the techniques used in this study. | 10.1002/jor.1100120314 |
pubmed_1132_6603 | PURPOSE OF REVIEW
Transcription co-regulator Cited2 is essential for mouse development. Recent work has shown that Cited2 plays important roles in normal hematopoiesis in fetal liver and adult bone marrow. This review focuses on the function of Cited2 in the maintenance of hematopoietic stem cells (HSCs) and its potential role in the metabolic regulation of HSCs.
RECENT FINDINGS
Fetal liver cells from Cited2 null embryos give rise to reduced numbers of hematopoietic colonies and display significantly impaired hematopoietic reconstitution capacity. In adult mice, conditional deletion of Cited2 markedly reduces the number of HSCs and compromises hematopoietic reconstitution in mice receiving a transplant of Cited2 deficient bone marrow cells. Additional deletion of Ink4a/Arf or p53 in a Cited2-deficient background restores HSC functionality. Meanwhile, Cited2 deficient HSCs display loss of quiescence, which can be partially rescued by additional deletion of hypoxia inducible factor-1α.
SUMMARY
Cited2 is an essential regulator in fetal liver and adult hematopoiesis. Further studies into the function of Cited2 and the underlying mechanism in the metabolic regulation of HSCs will provide a better understanding of the connection between energy metabolism and HSC quiescence and self-renewal. Investigations of the pathologic role of Cited2 in leukemogenesis may yield useful information in developing effective therapeutic strategies. | 10.1097/MOH.0b013e3283606022 |
pubmed_511_10312 | BACKGROUND
The spring ligament is an important medial arch stabilizer. However, when disrupted, it does not cause planovalgus deformity until the foot is cyclically loaded. We propose that the tibionavicular (TN) ligament plays an important role. However, this ligament is not imaged in routine magnetic resonance imaging (MRI) sequences.
METHODS
A prospective case-control study using a novel MRI sequence to image the TN ligament in 20 normal feet creating a baseline appearance of the ligament. We then scanned 20 patients with adult acquired flatfoot deformity (AAFD). All patients had weightbearing anteroposterior and lateral radiographs. We followed up patients, the end point being surgery or 18 months' follow-up.
RESULTS
The normal ligament was reliably identified on the novel sequences. It had a reproducible appearance in 2 views, and consistent length and width. Two groups of patients were identified in the AAFD cohort: Normal TN (11/20) (The mean Meary angle was 6.8 degrees) and Abnormal TN (9/20). The ligament was thickened proximally, with distal attenuation and intrasubstance edema. On sagittal sequence, it had dorsal bulging and high signal. The mean Meary angle was 13.2 degrees ( P = .013). All patients had posterior tibial tendon dysfunction and 8 had spring ligament complex attenuation. Five patients have undergone corrective surgery compared to none in the other group.
CONCLUSION
This study adds to the evidence that AAFD is multifactorial. With this imaging technique, we were able to reliably image the TN ligament. We hope that including this sequence into routine scanning will help us understand its role in flatfoot deformity. This poses the question of whether this structure will play a role in reconstructive surgery in future.
LEVEL OF EVIDENCE
Level II, prospective comparative study. | 10.1177/1071100718764680 |
pubmed_982_10604 | Biodegradation testing of commercial chemicals other than pesticides is generally performed using test guidelines of the Organization for Economic Cooperation and Development (OECD). We used test data submitted with US Premanufacture Notifications (PMNs) received from 1995 through 2005 to study performance of OECD biodegradation tests, as well as the overall testing strategy and guidance. Among the findings are that (1) ready biodegradation (RB) tests gave fairly consistent results relative to the pass/fail outcome, but not necessarily percent degradation; (2) the Zahn-Wellens test worked well in providing a quick measure of sorption potential, but aside from this, provided little useful information for the investigated chemicals beyond what was already available from RB tests; (3) the SCAS test sometimes gives lower % removal than continuous-feed simulation tests like OECD 303A; and (4) OECD 306 (marine biodegradation test) appeared less conservative than ordinary RB tests. Overall, the PMN data lend support to new OECD guidance that endorses the primary role of RB tests, but emphasizes simulation rather than inherent biodegradation tests as the next step. | 10.1016/j.chemosphere.2006.07.063 |
pubmed_457_5906 | BACKGROUND AND OBJECTIVES
Pseudomonas aeruginosa is a Gram-negative, aerobic bacterium found in water and soil. It is a normal flora in skin and gastrointestinal tract of human beings. P. aeruginosa as an opportunistic pathogen involved in nosocomial infections having multiple pathogenic factors and shows high rate of resistance to different antibiotics. The aim of this study was to identify the most important native medicinal plants of Iran effective on P. aeruginosa.
MATERIALS AND METHODS
All required information was obtained by searching keywords such as P. aeruginosa, medicinal plant extracts or essential oils in published articles in authentic scientific databases such as Science Direct, Wiley-Blackwell, Springer, Google scholar, Scientific Information Database (SID) and Magiran.
RESULTS
According to the literature review, our results showed 12 different native medicinal plants were effective against P. aeruginosa in Iran including Eucalyptus camadulensis, Marticaria chamomilla, Ferula gummosa Boiss, Lawsonia inermis, Ocimumgra tissimum, Allium sativum, Satureja hortensis L, Satureja bachtiarica Bunge, Satureja khuzestanica (Jamzad), Thymus daenensis Celak, Thymus carmanicus Jalals and Camellia sinensis.
CONCLUSION
Phytochemical analysis has shown that bioactive compounds of medicinal plants with their antioxidant and antimicrobial properties can be good alternatives for the synthetic medicines in food and drug industry. | pubmed_457_5906 |
pubmed_1074_11268 | BACKGROUND
Hemorrhage is a frequent cause of morbidity and mortality, possibly complicated by volatile anesthetics administered during surgical emergencies. Because methylene blue (MB) was suggested to reduce bleeding, we reasoned that it may improve resuscitation. We used a rat model of controlled and uncontrolled hemorrhage with fluid resuscitation, aiming at high versus low mean arterial pressure (MAP) to assess the role of early MB injection on survival and the effects of different anesthetics on outcome.
METHODS
Wistar male rats (n = 160) were subjected to 15-minute controlled and 60-minute uncontrolled hemorrhage and received lactated Ringer's solution replacement. Four sets (four groups per set, N = 10 per group) were anesthetized with halothane, isoflurane, sevoflurane, or ketamine (KET; control). Resuscitation-targeted MAP was 80 mm Hg in two groups per set and 40 mm Hg in two groups per set: one group received MB 25 mg/kg intravenously and the other one did not receive.
RESULTS
All parameters were worse in the higher target groups compared with the lower MAP target groups. MB improved variable outcomes in the treated compared with the nontreated groups, independent of the MAP or anesthesia agent: the amount of replacement volume, lung tissue xanthine oxidase activity, and rats' survival rates. Outcomes with and without MB were worse in the halothane set, followed, in ascending order, by sevoflurane, isoflurane, and KET.
CONCLUSIONS
MB improved parameters and survival rates after controlled and uncontrolled hemorrhage and fluid resuscitation, even in high MAP-resuscitated rats. KET seemed to be the best anesthetic choice among the four classic agents tested. The effects of balanced anesthesia and total intravenous anesthesia in similar conditions require additional studies. | 10.1097/TA.0b013e3181f8aa11 |
pubmed_1118_24425 | Tacrolimus (TAC) is an immunosuppressant widely used in kidney transplantation. TAC displays considerable interindividual variability in pharmacokinetics (PKs). Genetic and clinical factors play important roles in TAC PKs. We enrolled a total of 251 Chinese renal transplant recipients and conducted a genomewide association study (GWAS), linkage disequilibrium (LD), and one-way analysis of variance (ANOVA) to find genetic variants affecting log-transformed TAC trough blood concentration/dose ratio (log[C0 /D]). In addition, we performed dual luciferase reporter gene assays and multivariate regression models to evaluate the effect of the genetic variants. The GWAS results showed that all 23 genomewide significant single-nucleotide polymorphisms (p < 5 × 10-8 ) were located on chromosome 7, including CYP3A5*3. LD, conditional association analysis, and one-way ANOVA showed that rs75125371 T > C independently influenced TAC log(C0 /D). Dual luciferase reporter gene assays indicated that rs75125371 minor allele (C) was significantly associated with increased normalized luciferase activity than the major allele (T) in the Huh7 cells (p = 1.2 × 10-5 ) and HepaRG cells (p = 0.0097). A model inclusive of age, sex, hematocrit, CYP3A5*3, and rs75125371 explained 37.34% variance in TAC C0 . These results suggest that rs75125371 T > C is a functional and population-specific variant affecting TAC C0 in Chinese renal transplant recipients. | 10.1111/cts.13388 |
pubmed_48_13055 | Acoustic structure quantification (ASQ) is a recently developed technique widely used for detecting liver fibrosis. Ultrasound Nakagami parametric imaging based on the Nakagami distribution has been widely used to model echo amplitude distribution for tissue characterization. We explored the feasibility of using ultrasound Nakagami imaging as a model-based ASQ technique for assessing liver fibrosis. Standard ultrasound examinations were performed on 19 healthy volunteers and 91 patients with chronic hepatitis B and C (n = 110). Liver biopsy and ultrasound Nakagami imaging analysis were conducted to compare the METAVIR score and Nakagami parameter. The diagnostic value of ultrasound Nakagami imaging was evaluated using receiver operating characteristic (ROC) curves. The Nakagami parameter obtained through ultrasound Nakagami imaging decreased with an increase in the METAVIR score (p < 0.0001), representing an increase in the extent of pre-Rayleigh statistics for echo amplitude distribution. The area under the ROC curve (AUROC) was 0.88 for the diagnosis of any degree of fibrosis (≥F1), whereas it was 0.84, 0.69, and 0.67 for ≥F2, ≥F3, and ≥F4, respectively. Ultrasound Nakagami imaging is a model-based ASQ technique that can be beneficial for the clinical diagnosis of early liver fibrosis. | 10.1038/srep33075 |
pubmed_897_13741 | CONTEXT
Various Rhizoma coptidis are commonly used in clinical applications due to their strong antibacterial effect.
OBJECTIVE
The antibacterial effect of various R. coptidis were evaluated by microcalorimetry together with statistical analysis.
MATERIALS AND METHODS
The dried roots of Coptis chinensis Franch, Coptis deltoidea C.Y. Cheng et Hsiao, and Coptis teeta Wall (Ranunculaceae) were identified by Prof. Xiao-He Xiao. The herbs were tested using thermal activity monitor (TAM) air isothermal microcalorimeter, ampoule mode, to evaluate the biological activity. The dynamic energy metabolism information about the Staphylococcus aureus growth at 37°C was analyzed with principal component analysis.
RESULTS
From the principle component analysis on quantitative parameters, the action of various R. coptidis on S. aureus growth at 37°C could be easily evaluated by analyzing the change of values of the two main parameters: the growth rate constant of first stage (k(1)) and the maximum heat rating of the first stage (P(1)). And the results of paired t-test show that there were no notable differences between inhibitory ratios calculated with k(1) and that of P(1). Using microdilution method, the minimal inhibitory concentrations (MIC) of C. chinensis, C. deltoidea, and C. teeta were detected, and they were 77.8 ± 2, 116.6 ± 4, 93.3 ± 2 μg/mL, respectively.
DISCUSSION AND CONCLUSION
This work provided a useful method for the evaluation of antibacterial activity of various R. coptidis. | 10.3109/13880209.2010.523428 |
pubmed_250_21696 | The gastrointestinal tract of premature infants is a highly fragile organ due to numerous developmental immaturities. Exposure to luminal microbes in the first several weeks of these infants' lives may play a significant role in the development of short-term disease and may have profound effects on long-term health. New non-culture-based techniques are providing exciting new insights into how the intestinal microbiota of premature infants develops and relates to health. A brief summary of recent research in this area is presented, which may be adapted to nutritional strategies for disease prevention. | 10.1111/j.1753-4887.2008.00119.x |
pubmed_914_5226 | Bleeding complications in patients undergoing percutaneous coronary interventions (PCIs) are associated with increased risk of subsequent mortality. We undertook this study to characterize the subset of patients with bleeding complications who are at an increased risk of death within the first year after a PCI procedure. The study included 331 patients with bleeding complications among 9 954 patients who underwent PCI. The primary outcome analysis was 1-year mortality. Within the first year following PCI there were 39 deaths among 331 patients (11.8%), with bleeding complications and 240 deaths among 9 623 patients without bleeding complications (Kaplan-Meier estimates of 1-year mortality; 11.8% vs 2.5%, odds ratio 5.09, 95% confidence interval 3.76-6.90, P < 0.001). Time to death (median [25th-75th percentiles]) was 38.5 [7.2-125.9] days in patients with bleeding complications vs 137.1 [68.3-234.0] days in patients without bleeding complications (P < 0.001). Compared with survivors (n = 292), nonsurvivors (n = 39) had a significantly more adverse risk profile. The Cox proportional hazards model identified the elevated troponin level as the only independent correlate of 1-year mortality (hazard ratio = 2.35, 95% confidence interval 1.04-5.31, P = 0.039). In conclusion, patients with peri-PCI bleeding complications who die have a more adverse cardiovascular risk profile than patients with bleeding complications who survive the first year after PCI. Patients with bleeding complications and an elevated troponin level are at high risk of death within the first year following PCI. The majority of deaths in patients with peri-PCI bleeding occur within the first 3 months after PCI procedure. | 10.1007/s00380-009-1205-7 |
pubmed_442_3379 | Tobacco smoking is the leading cause of preventable death in the United States. Nicotine is the principal psychoactive ingredient in tobacco that causes addiction. The structures governing nicotine addiction, including those underlying withdrawal, are still being explored. Nicotine withdrawal is characterized by negative affective and cognitive symptoms that enhance relapse susceptibility, and suppressed dopaminergic transmission from ventral tegmental area (VTA) to target structures underlies behavioral symptoms of nicotine withdrawal. Agonist and partial agonist therapies help 1 in 4 treatment-seeking smokers at one-year post-cessation, and new targets are needed to more effectively aid smokers attempting to quit. Hypothalamic orexin/hypocretin neurons send excitatory projections to dopamine (DA)-producing neurons of VTA and modulate mesoaccumbal DA release. The effects of nicotinic receptor blockade, which is commonly used to precipitate withdrawal, on orexin neurons remain poorly investigated and present an attractive target for intervention. The present study sought to investigate the effects of nicotinic receptor blockade on hypothalamic orexin neurons using mecamylamine to precipitate withdrawal in rats. Separate groups of rats were treated with either chronic nicotine or saline for 7-days at which point effects of mecamylamine or saline on somatic signs and anxiety-like behavior were assessed. Finally, tissue from rats was harvested for immunofluorescent analysis of Fos within orexin neurons. Results demonstrate that nicotinic receptor blockade leads to reduced orexin cell activity, as indicated by lowered Fos-immunoreactivity, and suggest that this underlying cellular activity may be associated with symptoms of nicotine withdrawal as effects were most prominently observed in rats given chronic nicotine. We conclude from this study that orexin transmission becomes suppressed in rats upon nicotinic receptor blockade, and that behavioral symptoms associated with nicotine withdrawal may be aided by intervention upon orexinergic transmission. | pubmed_442_3379 |
pubmed_607_2811 | It is known that protein S, a vitamin K-dependent plasma protein, isolated from a human source, gives a closely spaced doublet on sodium dodecyl sulfate-polyacrylamide gel electrophoresis after reduction and that this heterogeneity in molecular size results from a limited proteolysis of protein S mediated by alpha-thrombin in human species. We found here that alpha-thrombin also rapidly converted single-chain bovine protein S to a nicked form, which consisted of the NH2-terminal segment containing gamma-carboxyglutamic acid and the COOH-terminal large segment bridged by a disulfide linkage(s). These two segments were isolated and chemically characterized after S-alkylation of the nicked protein S. The results suggest that the alpha-thrombin-catalyzed hydrolysis of protein S probably occurs at a peptide linkage (Arg-Ser) located in the NH2-terminal portion. The conversion of single-chain protein S to the nicked form was also mediated by plasma kallikrein and plasmin, in addition to alpha-chymotrypsin and trypsin. However, the alpha-thrombin-catalyzed conversion did not occur when calcium ions were added to the reaction mixture. | 10.1093/oxfordjournals.jbchem.a135512 |
pubmed_403_24625 | Background: Client-centred practice aims to involve the person in making decisions during the therapeutic intervention process, giving him or her a central and active role.Objectives: To analyze the effects of client-centred practice in occupational therapy on issues related to occupational performance and participation among people with stroke and traumatic brain injury.Material and methods: A systematic review of randomized clinical trials examining the effects of a client-centred practice carried out by occupational therapists in patients with stroke or traumatic brain injury aged over 18 years was conducted. PubMed, Web of Science, Scopus, OT Seeker, PsycINFO and EBSCO were used to retrieve potentially eligible publications.Results: Eight studies, from 294 identified, were included. The extracted data showed that the application of client-centred practice in occupational therapy improved satisfaction with occupational performance compared to conventional interventions. However, client-centred practice and conventional intervention had similar effects on functionality (Activities of Daily Living), life satisfaction and burden on caregivers.Conclusions and significance: Client-centred practice has the effect of achieving greater satisfaction with occupational performance. This suggests that client-centred practice in occupational therapy helps patients to accept the new limitations on their occupational performance. Further studies are needed to determine the effects of client-centred practice on other aspects. | 10.1080/11038128.2020.1856181 |
pubmed_285_23082 | OBJECTIVE
To establish a more reliable and accurate scale of perinatal maternal health literacy during perinatal period by selecting items form existing scale.
METHODS
Two rounds of inquiry were performed by 14 experts on mother and children to evaluate the necessary and importance of 56 items by Delphi method, in which 50 items were retained. Th en we proceeded a cross-sectional survey in 350 woman who just gave birth 1-3 days before. 10% of them were selected to retest aft er 1 week. Based on these data, we used 6 different methods to select items and kept those that could pass by at least 3 different methods. The methods used in data analysis were Chi-square test, correlation coefficient method (2 kinds), factor analysis, Cronbach α coefficient method and the retest reliability method.
RESULTS
The Person correlation coefficient was 0.507 (P=0.004). By using the 6 statistical methods, we deleted 9 items through Chi-square test, 25 items through correlation coefficient method 1, 1 item through correlation coefficient method 2, 19 items through Cronbach α coefficient method, 8 items through factor analysis and 37 items through retest reliability method. In the end, 33 items were retained for the novel scale of maternal health literacy during perinatal period.
CONCLUSION
Simplified novel scale is acquired, which need to do large efforts before extensive use, such as large sample survey, reliability and validity test. | 10.11817/j.issn.1672-7347.2015.05.017 |
pubmed_38_11772 | The ribosomal S6 kinase 2 (RSK2) is a member of the p90 ribosomal S6 kinase (p90RSK) family of proteins and plays a critical role in proliferation, cell cycle, and cell transformation. Here, we report that RSK2 phosphorylates caspase-8, and Thr-263 was identified as a novel caspase-8 phosphorylation site. In addition, we showed that EGF induces caspase-8 ubiquitination and degradation through the proteasome pathway, and phosphorylation of Thr-263 is associated with caspase-8 stability. Finally, RSK2 blocks Fas-induced apoptosis through its phosphorylation of caspase-8. These data provide a direct link between RSK2 and caspase-8 and identify a novel molecular mechanism for caspase-8 modulation by RSK2. | 10.1074/jbc.M110.172338 |
pubmed_815_5894 | Troglitazone is a new orally active hypoglycemic agent that has been shown to reduce insulin resistance and hyperinsulinemia in both diabetic animal models and non-insulin-dependent diabetes mellitus (NIDDM) subjects. To determine whether this drug could prevent the development of fructose-induced insulin resistance and related abnormalities, we studied the effects of troglitazone on the insulin resistance induced by fructose feeding in rats. Normal male Sprague-Dawley rats were fed a high-fructose diet for 3 weeks with and without troglitazone as a food admixture (0.2%) or were fed normal chow to serve as a control group. In vivo insulin resistnace was measured by the euglycemic hyperinsulinemic clamp technique at two different insulin infusion rates, 29 (submaximal stimulation) and 290 (maximal stimulation) pmol.kg-1.min-1. Fructose feeding markedly reduced submaximal glucose disposal rate (GDR) (113.8 +/- 8.3 vs. 176.0 +/- 5.6 mumol.kg-1.min-1, P < 0.05) and maximal GDR (255.9 +/- 5.6 vs. 313.6 +/- 10.5 mumol.kg-1.min-1, P < 0.05), reduced the suppressibility of submaximal hepatic glucose production (HGP; 45.5 +/- 5.0 vs. 11.7 +/- 5.0 mumol.kg-1.min-1, P < 0.05), and resulted in hypertriglyceridemia and hypertension. Troglitazone treatment completely restored the GDR (submaximal 158.2 +/- 5.6, maximal 305.3 +/- 6.1 mumol.kg-1.min-1) and submaximal HGP (9.4 +/- 2.8 mumol.kg-1.min-1) to control levels and also normalized the elevated plasma triglyceride concentration and systolic blood pressure levels in fructose-fed rats.(ABSTRACT TRUNCATED AT 250 WORDS) | 10.2337/diab.43.12.1435 |
pubmed_260_8305 | A pure testicular rhabdomyosarcoma in infants and children is a very rare type of tumor. A 9-month-old baby boy who presented with a painless right testicular swelling underwent right inguinal radical orchiectomy with suspicion of testicular malignancy. This case was confirmed as an embryonal rhabdomyosarcoma by the histopathologic and immunohistochemical findings. We report on the case with reviews of the relevant literature. | 10.1016/j.urology.2007.03.021 |
pubmed_432_13779 | Computed tomography (CT) was performed on 30 patients with herniated lumbar discs before chemonucleolysis and at three and 12 months postinjection. At three months the compression produced by the herniated disc was reduced in 20 of the 30 patients; at 12 months there was complete relief of compression in all but four patients. Twenty-four patients developed diffuse bulging of the annulus. There was good correlation between the clinical results at three months and the reduction in compression as shown by the CT scan. At 12 months, no correlation was found between the remaining focal abnormalities and the clinical result. None of the patients developed epidural fibrosis. Chemonucleolysis has thus been shown to be an effective treatment of herniated lumbar discs, but it is definitely not indicated in cases where compression of the nerve root or dural sac is due to a bulging annulus. | pubmed_432_13779 |
pubmed_49_19380 | A new model for experimental studies of substances influencing porphyrin metabolism has been created. The model is formed by yeast Saccharomyces cerevisiae (RIBM-75) grown semiaerobically. The main advantages of this model include simple evocation of porphyria (intracellular accumulation of porphyrins in semiaerobic conditions) and direct measurement of experimental values (intracellular and extracellular concentrations of porphyrins). The porphyrinostatic effects of drugs can be assessed on the basis of sum of experimental values. The ratio of experimental criteria enables us to compare the influence of drugs on porphyrin permeation across the cellular membrane. Antimalarials, chloroquine and pyrimethamine, used or tested for therapy of chronic liver porphyria, have been tested on the model. The experiments showed that both chloroquine and pyrimethamine inhibited porphyrin synthesis. This effect can represent the proper therapeutical action of both drugs, which has not been known so far. Chloroquine releases the intracellular porphyrins in yeast similarly as it does in hepatocytes. However, pyrimethamine causes intracellular accumulation of porphyrins booth in yeast and hepatocytes. | pubmed_49_19380 |
pubmed_219_20156 | Mutants of P450-BM3 evolved by directed evolution are excellent catalysts in the CH-activating oxidative hydroxylation of 1-tetralone derivatives and of indanone, with unusually high regio- and enantioselectivity being observed. Similar results were achieved in the oxidative hydroxylation of tetralin and indane. The products are useful building blocks in the synthesis of a number of biologically active compounds. | 10.1039/c4cc04925j |
pubmed_525_10350 | A crucial element of many gene functions is protein-induced DNA bending. Computer-generated models of such bending have generally been derived by using a presumed bending angle for DNA. Here we describe a knowledge-based docking strategy for modeling the structure of bent DNA recognized by a major groove-inserting alpha-helix of proteins with a helix-turn-helix (HTH) motif. The method encompasses a series of molecular mechanics and dynamics simulations and incorporates two experimentally derived distance restraints: one between the recognition helix and DNA, the other between respective sites of protein and DNA involved in chemical modification-enabled nuclease scissions. During simulation, a DNA initially placed at a distance was "steered" by these restraints to dock with the binding protein and bends. Three prototype systems of dimerized HTH DNA binding were examined: the catabolite gene activator protein (CAP), the phage 434 repressor (Rep), and the factor for inversion stimulation (Fis). For CAP-DNA and Rep-DNA, the root mean square differences between model and x-ray structures in nonhydrogen atoms of the DNA core domain were 2.5 A and 1.6 A, respectively. An experimental structure of Fis-DNA is not yet available, but the predicted asymmetrical bending and the bending angle agree with results from a recent biochemical analysis. | 10.1016/S0006-3495(99)76971-7 |
pubmed_699_15770 | Acinetobacter baumannii is a common causative agent of nosocomial infections, with a mortality rate of 43% in infected patients. Due to the emergence of multidrug-resistant (MDR) strains, vaccine development has become necessary. Since the 34 kDa outer membrane protein Omp34 has been identified as a potential vaccine target, we implemented a hybrid antigen approach to target its extracellular loops. Using bioinformatic and structural analyses, we selected Loop 3 from Omp34 and displayed it on the loopless C-lobe (LCL) of TbpB of Neisseria meningitidis. The hybrid antigen and the LCL were produced and used to immunize mice for passive and active immunization and challenge experiments in which the reactivity of the sera was assessed by ELISAs, the bacterial load in the tissues measured and the survival of immunized mice compared. LCL was ineffective in immunization against A. baumannii thus the resulting immunity was due to the presence of Omp34 loop 3. It resulted in increased survival and a reduced bacterial load in the tissues compared to the control groups. The findings indicate that the immunogenicity of Omp34 loops can induce protection against A. baumannii infection, and it could probably be used as a vaccine candidate to control the pathogenesis of A. baumannii. | 10.1016/j.intimp.2022.109013 |
pubmed_678_17655 | Short-lasting rhythmic activity in intracranial electroencephalogram (iEEG) in the frequency range of 80 to 500 Hz is regarded to be a promising biomarker of epileptogenicity. This activity is referred to as high-frequency oscillation (HFO), and its detection from iEEG is considered the first step to several applications. In this study, several multi-channel algorithms for HFO detection are proposed. With the proposed multi-channel statistics and threshold determination scheme, the algorithms allow HFO detection to be performed without breaking the iEEG channel structure and the detection threshold to be determined automatically. Experimental simulation results illustrate the advantage of the proposed algorithms over existing single-channel-based approaches. | 10.1109/EMBC.2016.7590858 |
pubmed_572_13968 | PURPOSE
To determine the association of age-related maculopathy susceptibility2 (ARMS2) gene polymorphisms with the 3-year outcomes of photodynamic therapy (PDT) in wet age-related macular degeneration (wet AMD).
METHODS
The single nucleotide polymorphism (SNP) at rs10490924 in the ARMS2 gene of 65 patients with wet AMD who underwent PDT was genotyped using the TaqMan assay. The clinical characteristics and the outcomes of PDT were compared among the three genotypes at rs10490924. A multivariate regression analysis was performed to evaluate the influence of the clinical cofactors on the association of rs10490924 with the visual outcome at 36 months after the first PDT.
RESULTS
A significant difference was found among the genotypes in the age and the baseline lesion size. The patients with the GG genotype showed a significant improvement in vision, and the patients with the TT genotype showed a significant worsening of vision at all time points measured after the initial PDT. In the multivariate regression analysis, the number of the G allele at rs10490924 was associated with a significantly greater improvement in the baseline best-corrected visual acuity (BCVA) at 36 months after the first PDT.
CONCLUSIONS
ARMS2 variants are likely associated with the 3-year outcomes of PDT in patients with wet AMD. | pubmed_572_13968 |
pubmed_960_18339 | In this article, a comprehensive picture of the oxidation of protein pharmaceuticals by peroxides is developed based on our earlier computational and experimental studies. We propose a new mechanism, the water-mediated mechanism, for the oxidation of methionine residues, and it has been shown to satisfy all available experimental data including new data reported here. Based on the water-mediated mechanism, we found a structural property, average 2-shell water coordination number, that correlates well to the relative rates of oxidation of methionine groups. We used this to study the oxidation of granulocyte colony-stimulating factor (G-CSF) and 1-34 human parathyroid hormone hPTH(1-34). We believe that this comprehensive picture should aid researchers in the pharmaceutical sciences to develop solvent formulations for therapeutic proteins in a more rational way. | 10.1002/jps.20207 |
pubmed_822_12256 | Aniseed (Pimpinella anisum L., Apiaceae) and its essential oil (EO) have been widely used. Because there are some data about the impact of aniseed EO on drug effects, this survey aimed to assess the potential of pharmacokinetic herb-drug interaction between aniseed EO and acetaminophen and caffeine in mice. The chemical analysis (gas chromatography-mass spectrometry) of aniseed EO has confirmed trans-anethole (87.96%) as the main component. The pharmacokinetic studies of intraperitoneally (i.p.) and orally applied acetaminophen (200 mg/kg) and caffeine (20 mg/kg) were performed in mice after 5 days of oral treatment with human equivalent dose of aniseed EO (0.3 mg/kg/day). The analysis of pharmacokinetic data showed that in the group treated by aniseed EO, the significant decrease in the peak plasma concentration of acetaminophen after oral application (p = 0.024) was revealed when compared with control group and the reduction of systemic exposure to the drug after oral application (74 ± 32% vs. 85 ± 35% in the control) was noted. The bioavailability of orally applied caffeine was also significantly decreased (p = 0.022) after the EO treatment in comparison with the control (57 ± 24% vs. 101 ± 29%). Therefore, the compromised therapeutic efficacy of acetaminophen and caffeine during the usage of aniseed EO preparations should be considered. | 10.1002/ptr.5523 |
pubmed_122_6959 | BACKGROUND
Low-risk neuroblastomas have favorable biologic characteristics. Children Oncology Group (COG) proposed that surgical resection of the primary tumor was sufficient. We evaluated the long-term prognosis of surgery alone for patients with low-risk neuroblastoma in China.
METHODS
A total of 34 patients with low-risk neuroblastoma were treated in our center between Jan 2009 and Dec 2013. The medical records of these patients were reviewed.
RESULTS
The primary lesion was located in the adrenal gland in 19 patients, the retroperitoneum in 5, the posterior mediastinum in 9 and the neck in 1. The tumor diameters and volumes were 1.80-10.0 cm (average 5.5 ± 2.3 cm) and 1.28-424.10 cm3 (average 58.81 ± 92.00 cm3), respectively. The stages of the patients were as follows: stage I in 25, stage II in 7, and stage IVs in 2. All patients were in the low-risk group according to COG risk stratification criteria. No patients showed MYCN amplification. The primary tumors of all patients were completely resected. Nine adrenal tumors were completely resected by laparoscopy. All patients were successfully followed for 66-115 (average 89.71 ± 16.17) months. Recurrence was observed in 4 patients. In addition to one local recurrence, another three recurrences were metastases. The lesions were effectively controlled in all patients with recurrences. All patients survived, including 28 cases of tumor-free survival; the 4-year overall and event-free survival rates were both 100%.
CONCLUSIONS
Surgery alone is a safe and effective treatment strategy for low-risk neuroblastoma. Recurrent lesions may be controlled and treated by rescue chemotherapy and surgery. | 10.1007/s12519-018-0205-z |
pubmed_1005_17186 | PURPOSE
It is assumed that the width of the optic nerve sheath diameter (ONSD) is dependent on intracranial pressure (ICP) and pulsatility and thus constitutes a non-invasively accessible "window" for qualitative assessment of ICP. Data on the correlation to invasively measured ICP in children are scarce and have often been obtained from sedated patients in intensive care unit (ICU) or intraoperatively. We report on a mixed cohort of pediatric neurosurgical patients, ICP and ONSD measurements were available from both sedated and awake children, only a minority from ICU patients.
METHODS
Seventy-two children were investigated. Ultrasound ONSD determination was performed immediately prior to invasive ICP measurement and the mean binocular ONSD was compared with ICP. The investigations were performed in children awake, sedated, or under general anesthesia.
RESULTS
In the entire patient cohort, the correlation between ONSD and ICP was good (r = 0.52, p < 0.01). Children > 1 year revealed a better correlation (r = 0.63; p < 0.01) and those ≤ 1 year did worse (r = 0.21). Infants with open fontanelle had no correlation. In the entire cohort, the best ONSD cut-off value for detecting ICP ≥ 15 and ≥ 20 mmHg was 5.28 and 5.57 mm (OR 22.5 and 7.2, AUC 0.782 and 0.733).
CONCLUSION
Transorbital ultrasound measurement of ONSD is a reliable non-invasive technique to assess increased ICP in children in every clinical situation; however, the impact of age and fontanelle status needs to be considered. ONSD thresholds enable qualitative first orientation regarding ICP categories with a very satisfying diagnostic accuracy. | 10.1007/s00381-019-04266-1 |
pubmed_1001_1080 | PURPOSE
To measure the microtensile bond strength to enamel and dentin of three self-etching adhesives in comparison with a total-etch two-step system as a control.
MATERIALS AND METHODS
A total of 40 extracted human molars were stored in saline solution until use, then divided into 4 groups of 10 teeth (one group per adhesive system). Half of each of these groups underwent bond strength tests on enamel, and the other half was used for adhesion testing on dentin. The following experimental groups (n = 5) were then formed: E(1) Adper Prompt-L-Pop (AP, 3M ESPE) on enamel; E(2) Xeno CF II (X, Sanking Kogyo) on enamel; E(3) AdheSE (AS, Ivoclar-Vivadent) on enamel; E(4) Excite (EX, Ivoclar-Vivadent) on enamel; D(1) AP on dentin; D(2): X on dentin; D(3) AS on dentin; D(4) EX on dentin. Each tooth yielded 15 to 20 sticks about 0.9 x 0.9 mm in cross-sectional area for microtensile testing. Specimens were loaded in tension at a crosshead speed of 0.5 mm/minute, and bond strength at failure was calculated in MPa. A two-way ANOVA was applied to test for significance of the differences among the groups.
RESULTS
The bond strength values of Excite (the control) were significantly higher than those of the test products on enamel (42.92+/-4.8 MPa) and on dentin (45.80+/-5.79 MPa). The self-etching adhesives AdheSE (28.48+/-4.71 MPa) and Xeno CF II (27.22+/-2.74 MPa) revealed significantly stronger adhesion than Adper Prompt-L-Pop (20.16+/-2.07 MPa) on dentin. On enamel, all self-etching test materials performed similarly. The substrate did not appear to have a significant influence on adhesion, as each material reached comparable levels of bond strength on enamel and dentin.
CONCLUSION
On both substrates the self-etching adhesives tested performed significantly worse than did the total-etch system. | pubmed_1001_1080 |
pubmed_584_8942 | OBJECTIVE
To characterise the prevalence of, and changes in, coronary heart disease (CHD) among men and women aged between 64 and 71 years in the 1990s.
DESIGN
A study of clinical epidemiology involving two cohorts of elderly persons in 1990-1991 and 1998-1999.
SETTING
Primary health care in the municipality of Lieto in southwestern Finland.
SUBJECTS
Persons between 64 and 71 years of age in the southwest of Finland in 1990-1991 and 1998-1999.
MAIN OUTCOME MEASURES
The occurrences of CHD were estimated using the history of a previous myocardial infarction or coronary revascularisation procedure evident in the medical records and with ischaemia or infarction as established on ECG according to the Whitehall criteria.
RESULTS
The prevalence of 'probable' CHD decreased among men and women aged between 64 and 71 years, whereas the prevalence of 'possible' CHD decreased among women alone. Silent myocardial infarctions were common among women of both cohorts. Many more men of the second cohort, compared to the first one, had undergone a coronary angioplasty or bypass operation.
CONCLUSION
The prevalence of CHD decreased among elderly women more clearly than among young elderly men. The favourable development illustrating a decrease in the prevalence of CHD among women should be sustained, while health promotion activities will need to be directed more actively towards men. | 10.1080/02813430310001013 |
pubmed_598_1143 | BACKGROUND
Hodgkin's lymphoma (HL) and anaplastic large-cell lymphoma (ALCL) are the two most common tumors expressing CD30. Internationally, a clinical study that is being conducted involving adults with recurrent or refractory HL or ALCL suggests efficacy of brentuximab vedotin (SGN-35). Pediatric patients should be given medicines that have been appropriately evaluated for their use. In the past, however, new approved drugs have been used for pediatric patients without the confirmation of safety and efficacy in pediatric patients. Therefore, it is important to examine the safety and efficacy of SGN-35 in Japanese children.
METHODS
Phase I clinical study of SGN-35 involving children with recurrent or refractory CD30-positive Hodgkin's lymphoma or systemic anaplastic large cell lymphoma (BV-HLALCL study) is being conducted for pediatric patients in order to evaluate the safety, feasibility and preliminary clinical effectiveness of brentuximab vedotin. SGN-35 is intravenously administered on Day 1 of each cycle (21 days/cycle). The dose of SGN-35 is calculated based on the body weight at the baseline. The primary endpoint is dose limiting toxicity and incidence of adverse events. The secondary endpoints are pharmacokinetics, response rate, complete remission rate, response duration, progression-free survival and event-free survival. The reduction rate of tumor will be calculated according to revised response criteria for malignant lymphoma for measurable tumor. Six pediatric patients will be enrolled in this study.
DISCUSSION
This study aims to expand indication of SGN-35 in Japan by assessing its safety and efficacy in pediatric patients.
TRIAL REGISTRATION
JMACCT ID: JMA-IIA00229 . Registered on 17 Nov 2015. | 10.1186/s12885-018-4042-1 |
pubmed_963_7266 | Pulmonary embolism is a relative common, potentially fatal disorder that clinicians have difficulty detecting and difficulty diagnosing. Deep venous thrombosis (DVT) is the most important source of thrombi. Early and accurate diagnosis is essential for efficient therapy. Therapy is based on long-term anticoagulation and has an important impact on the mortality and morbidity of pulmonary embolism. For the diagnosis of pulmonary embolism, the ventilation/perfusion (V/Q) scan is still the first examination in many instances. A normal V/Q scan or the combination of a low probability scan and a low clinical suspicion are associated with a prevalence of pulmonary embolism of 4%. The combination of a high-probability V/Q scan and a strong clinical suspicion has a prevalence of pulmonary embolism of 96%. All other results should be considered as non-diagnostic. However, the number of non-diagnostic V/Q examinations can be as high as 70%. Nevertheless, an additional pulmonary angiography will be performed in only in 15% of these cases. In the low pre-test probability group (poor clinical suspicion, absence of risk factors and no medical history) the V/Q scan is useful as a screening test ("rule-out" strategy). When the pre-test probability is higher or in other cases in which early diagnosis is necessary ("rule-in" strategy), a contrast-enhanced spiral CT of the pulmonary arteries (possibly in combination with ultrasonography of the lower limbs) is the most accurate examination. | pubmed_963_7266 |
pubmed_89_405 | AIMS
To introduce and compare the modified laparoscopic Vecchietti and Davydov techniques for vaginoplasty in patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Moreover, the long-term treatment of vaginal agenesis was followed-up.
METHODS
This comparative retrospective cohort study enrolled a total of 53 women with MRKH syndrome. The patients underwent surgical creation of a neovagina including 32 patients who underwent the modified laparoscopic Vecchietti technique, and 21 patients who underwent the modified laparoscopic Davydov technique from January 2009 to February 2019. The perioperative parameters, complications, anatomical, and functional outcomes of the two groups were compared. Patients' sexual functions were evaluated over a long-term follow-up using the female sexual function index (FSFI) and the revised female sexual distress scale (FSDS-R).
RESULTS
The medians (25th-75th) of the surgery duration for modified Vecchietti procedures was 50.0 (40.0-59.0) minutes, comparing to 135.0 (117.5-162.5) min for Davydov procedures (p < 0.001). The intraoperative blood loss was 20 (7.5-20.0) mL versus 50.0 (50.0-100.0) mL using the modified Vecchietti and Davydov approaches (p < 0.001), respectively. In the 39 follow-up cases, the lengths of the neovagina of the patients for Vecchietti group versus Davydov group were 7.9 ± 1.0 cm versus 8.6 ± 1.2 cm at 6 months after the vaginoplasty and 8.3 ± 0.7 cm versus 8.5 ± 0.9 cm after 2 years. There was no statistical difference in the FSFI and FSDS-R scores between the two groups.
CONCLUSIONS
Both the modified Davydov and Vecchietti laparoscopic procedures successfully achieved optimal anatomic and functional outcomes in treatments of vaginal agenesis. The modified Vecchietti technique is relatively simpler than the modified Davydov technique. | 10.1111/jog.15262 |
pubmed_132_18087 | Tularemia is an infection caused by Francisella tularensis with a worldwide distribution and diverse clinical manifestations. In recent years, tularemia cases are increasing in Turkey, with a special attention to Marmara, western Blacksea and Central Anatolia regions. The aim of this study was to evaluate tularemia cases admitted to our hospital during an outbreak emerged at Central Anatolia between December 2009 and September 2010, making a point for the disease. A total of 32 patients (17 female, 15 male; age range: 15-80 years, mean age: 41 ± 16 years) with fever, sore throat, cervical mass and failure to respond to beta-lactam antibiotics, were followed up with the preliminary diagnosis of tularemia. The diagnosis was confirmed by specific laboratory tests. Serum samples were obtained from 25 patients and in 17 (68%) of them microagglutination test yielded positive result (≥ 1/160) in their first serum samples. All of the 8 patients who had negative results in their first samples (< 1/160), revealed seroconversion in their second samples. In 10 (91%) of the 11 patients from whom lymph node aspirates were obtained, PCR performed with species specific (tul4) primers yielded positivity and subspecies differentiation done by RD1 primers identified the agent as F.tularensis subspecies holarctica. F.tularensis growth was not detected in the cultures of lymph aspirates and/or throat swabs of the cases (n= 16). All the patients had oropharyngeal tularemia and eight of them also had oculoglandular form. The mean duration of the symptoms were 25.6 ± 17.2 (2-60) days. They had a history of oral intake of contaminated water. Cervical or submandibular lymphadenopathy were detected in all patients. One patient had cervical abscess and the other one had erythema nodosum. Elevated sedimentation rate was found in 26 (81.3%) patients and elevated CRP in 24 (75%) patients. Spontaneous drainage was detected in nine cases during follow-up. Lymph node aspiration was performed in patients when fluctuation was detected. Streptomycin 2 g/day for 10 days was given to 21 patients and doxycycline 2 x 100 mg for 14 days was given to 11 patients. Twelve (37.5%) patients received further antibiotic treatment since they failed to respond to the first therapy. Of the patients, 21 recovered completely and two patients had lymph node excision. No severe complications were observed. The patients who applied to the hospital within 10 days of the initiation of the symptoms were treated successfully, while the others that applied later were not. In conclusion, tularemia which is an endemic disease in Turkey, should be kept in mind in patients with fever, sore throat and lymphadenopathy. | pubmed_132_18087 |
pubmed_272_20789 | Fetal central nervous system abnormalities encompass a variety of lesions. Most of the anomalies are seen in association with an increased incidence of fetal aneuploidy and an increase in other anomalies both within and outside of the central nervous system. These associated findings and the underlying lesion all have a role in the eventual prognosis for the ongoing pregnancy. The antenatal diagnosis of a central nervous system abnormality should prompt a careful search for other defects, and consideration should be given for genetic evaluation and testing. | 10.1016/s0095-5108(05)70053-1 |
pubmed_1094_12187 | Extracellular matrix (ECM) molecules have several functions in pancreatic islets, including provision of mechanical support and prevention of cytotoxicity during inflammation. During islet isolation, ECM connections are damaged, and are not restored after encapsulation and transplantation. Inclusion of specific combinations of collagen type IV and laminins in immunoisolating capsules can enhance survival of pancreatic islets. Here we investigated whether ECM can also enhance survival and lower susceptibility of human islets to cytokine-mediated cytotoxicity. To this end, human islets were encapsulated in alginate with collagen IV and either RGD, LRE or PDSGR, i.e. laminin sequences. Islets in capsules without ECM served as control. The encapsulated islets were exposed to IL-1β, IFN-γ and TNF-α for 24 and 72 h. All combinations of ECM improved the islet cell survival, and reduced necrosis and apoptosis after cytokine exposure (P < 0.01). Collagen IV-RGD and collagen IV-LRE reduced danger-associated molecular patterns (DAMPs) release from islets (P < 0.05). Moreover, collagen IV-RGD and collagen IV-PDSGR, but not collagen IV-LRE, reduced NO release from encapsulated human islets (P < 0.05). This reduction correlated with a higher oxygen consumption rate (OCR) of islets in capsules containing collagen IV-RGD and collagen IV-PDSGR. Islets in capsules with collagen IV-LRE showed more dysfunction, and OCR was not different from islets in control capsules without ECM. Our study demonstrates that incorporation of specific ECM molecules such as collagen type IV with the laminin sequences RGD and PDSGR in immunoisolated islets can protect against cytokine toxicity. | 10.1002/term.2472 |
pubmed_379_18012 | Enhancement of human immunodeficiency virus (HIV) infection by complement alone or in conjunction with antibodies was studied experimentally and theoretically. Experimental studies showed that while HIV-positive sera neutralize HIV infection, the addition of fresh complement abrogated neutralization and could even cause enhancement. Enhancement was blocked by anti-complement receptor 2 antibodies, and infection under enhancing conditions could be blocked by soluble CD4. Antibody-dependent complement-mediated enhancement (C'ADE) was dependent on the alternative complement activation pathway, as factor B-deficient serum could enhance only after the addition of factor B. The observed enhancement was also antibody dependent, since the addition of antibodies increased the level of enhancement. Under C'ADE conditions, infection reached a plateau within 5 min and was not caused by activation of cells by factors in the human serum. On the contrary, preincubation of cells with complement decreased the level of enhancement. A theoretical model of HIV infection in vitro which exhibited similar enhancement in an antibody- and complement concentration-dependent way was developed. Model studies indicated that the enhanced infection process could be explained by the fact that virions, because of complement deposition on the surface, bind more efficiently to cells. The model also indicated that the saturation of the enhanced infection process seen after a few minutes could be caused by saturation of the complement receptors. The effect of neutralizing antibodies can thus be overcome by the enhancing effect of complement that facilitates the contact between gp120 and CD4. These studies demonstrate that the main features of the complement-dependent enhancement phenomenon can be understood in terms of a simple mathematical model. | 10.1128/JVI.69.4.2393-2400.1995 |
pubmed_23_9832 | OBJECTIVE
To compare nutrition knowledge and food intake in 7-y-old intervention and control children in an atherosclerosis risk factor intervention trial after 6.5 y of nutrition counselling given to the parents.
DESIGN, SUBJECTS AND METHODS
Intervention families in the Special Turku Coronary Risk Factor Intervention Project received child-oriented nutritional counselling one to three times a year since child's age of 7 months, aimed at reduced saturated fat and cholesterol intake. Children's nutrition knowledge was analysed in a time-restricted cohort of 70 seven-y-old (34 boys) intervention children and 70 control children (40 boys) with a picture identification test. For comparison, children's food intake was evaluated using scores developed for the project that reflected quality and quantity of fat and quantity of salt in children's two or three 4-day food diaries recorded between 5.5 and 7 y of age.
RESULTS
Child-targeted nutrition counselling of the intervention families only slightly increased intervention children's knowledge of heart-healthy foods (42.6% vs 34.9% correct answers by the intervention and control children, P = 0.057). Only < or = 20% of the children were able to adequately justify their answers in the test. The food diaries of the intervention children comprised more foods low in saturated fat and high in unsaturated fat than those of the control children (57.1% vs 41.7% of the maximum score for low fat foods, P = 0.0001; 48.9% vs 37.7% for high unsaturated fat foods, P = 0.0009, respectively), but the intervention and control children consumed similar amounts of low-salt foods (P = 0.23). Nutrition knowledge and food use scores correlated poorly (r = -0.20-0.35).
CONCLUSIONS
Child-targeted nutrition counselling repeatedly given to the parents during and after child's infancy strongly influenced food choice scores of the 5.5-7-y-old children but failed to influence children's salt intake or scores in a nutrition knowledge picture test. | 10.1038/sj.ejcn.1601153 |
pubmed_365_15859 | An ultrastructural study of spermatozoa in a series of 247 severely asthenozoospermic patients disclosed two kinds of anomalies. The first was dysplasia of the fibrous sheath, a primary defect of spermatozoa with hypertrophy and hyperplasia of the fibrous sheath, associated axonemal anomalies, familial incidence and chronic respiratory disease. The patients could be divided into two subgroups: the complete form (all spermatozoa affected) and the incomplete form (alterations in 70-80% spermatozoa). There were no spontaneous or in-vitro fertilization (IVF) pregnancies. Intracytoplasmic sperm injection (ICSI) in six patients resulted in successful fertilizations, but only two pregnancies were obtained. These features configure a phenotype that suggests a genetic origin. The second anomaly was non-specific flagellar anomaly (NSFA), random secondary flagellar alterations affecting variable numbers of spermatozoa, without respiratory disease or familial incidence. 54 men with NSFA were followed for 2-6 years. Of these, 18 achieved conception, either spontaneous or by means of assisted fertilization, followed by 14 pregnancies and 12 live births. Their sperm motility significantly increased during the follow-up period. In the remaining 36 men motility did not change during the follow-up period and there were no fertilizations or pregnancies. We conclude that in severe asthenozoospermia, ultrastructural examination of spermatozoa has an effective prognostic value, identifying two syndromes with very different flagellar alterations and fertility potentials. | 10.1093/humrep/13.9.2521 |
pubmed_61_10716 | BACKGROUND & OBJECTIVE
This study was to compare the protein expression profiles between retinoic acid (RA) resistant and sensitive acute promyelocytic leukemia (APL) cells by proteomic research method.
METHODS
Total cellular proteins extracted from a RA sensitive cell line NB4 and a RA resistant cell line MR2 were separated by two-dimensional (2D) polyacrylamide gel electrophoresis (PAGE). High quality 2D-PAGE protein profiles were obtained and analyzed by PDQuest v7.1 analysis software to screen differentially expressed protein spots. Those sports were identified by mass spectrometry.
RESULTS
2-DE patterns of APL cell lines with high-resolution and reproducibility were obtained. The average spots for MR2 and NB4 cells were 890+/-45 and 912+/-56, respectively. 57 significantly differentially expressed protein spots were screened, among which 23 protein spots were identified to be up-regulated and 34 down-regulated in MR2 cells compared with NB4 cells. Ten proteins were identified by mass spectrometry, with a successful identification rate of 70%. The identified proteins could be classified into different categories: oncogenes,cell cycle regulator and signal transducer.
CONCLUSION
The utilization of 2D-PAGE is effective in identifying the protein expression profiles between RA resistant and sensitive APL cells, therefore this study may provide a novel clue to elucidate the drug resistant mechanisms of all-trans retinoic acid. | pubmed_61_10716 |
pubmed_982_7103 | BACKGROUND
Interaction between advanced glycosylation end products (AGEs) and receptor for AGEs (RAGE) in vessel wall may lead to inflammation, smooth muscle cell proliferation, and extracellular matrix production, culminating in exaggerated intimal hyperplasia and restenosis. We investigated the possibility that single nucleotide polymorphisms of the genes encoding RAGE are associated with in-stent restenosis after coronary stenting.
METHODS
Our study included 334 consecutive non-diabetic male patients with symptomatic coronary artery disease who underwent bare metal stent implantation. Follow-up angiography was performed in 297 patients (88.9%), 6 months after intervention. We screened -1106T-->C, -443T-->C, -388T-->A, -257G-->A, +557G-->A and +1704G-->T RAGE polymorphisms in these patients. Genotyping was performed by single base extension with amplifying primers and probes for TaqMan.
RESULTS
A total of 355 target lesions were evaluated, in 297 patients. There was no significant association of the -1106T-->C, -443T-->C, -388T-->A, -257G-->A, +557G-->A or +1704G-->T polymorphisms with in-stent restenosis after coronary artery stenting. We did not observe a significant difference between the genotype distributions and the rates of angiographic restenosis between the polymorphisms. In a multivariate analysis of angiographic restenosis, we examined the possible influence of the baseline, lesion-related, and procedural variables. After adjustment for these potentially confounding factors, the multivariate analysis did not reveal an association of polymorphism with angiographic restenosis.
CONCLUSION
Our observation suggests that the RAGE gene polymorphism is not associated with in-stent restenosis after coronary artery stenting in non-diabetic patients in the Korean population. | 10.1159/000095516 |
pubmed_402_1617 | A 23-year-old woman who was in the ninth month of pregnancy suffered a head injury by falling from the stairs. She regained consciousness in the ambulance car, however, could not recall anything about herself. The morning after, her neurological examination disclosed no abnormal findings. She was alert, spatially oriented, but unable to recall any personal information about herself, her work and family contexts. The results of WAIS-R and WMS were within normal range, and she showed a dissociation between a detailed knowledge of public events and famous people and a complete loss of autobiographic information. EEG and brain MRI were normal. Memory loss spontaneously recovered following several months, and 8 month later, the retrograde amnesia had almost resolved. Although it is well-known that autobiographic amnesia usually attributed to psychogenic etiology, the differential diagnosis of the similar selective retrograde amnesia by organic etiology is important. | pubmed_402_1617 |
pubmed_321_5269 | Autophagy allows the degradation of cytosolic endogenous and exogenous material in the lysosome. Substrates are engulfed by double-membrane vesicles, coined autophagosomes, which subsequently fuse with lysosomes. Depending on the involvement of specific receptor proteins, autophagy occurs in a selective or nonselective manner. While this process is well understood at the level of bulky cargo such as mitochondria and bacteria, we know very little about individual proteins and protein complexes that are engulfed and degraded by autophagy. In contrast to the critical role of autophagy in balancing proteostasis, our current knowledge of the autophagic degradome is very limited. Here, we combined proximity labeling with quantitative proteomics to systematically map the protein inventory of autophagosomes. Using this strategy, we uncovered a basal, housekeeping mitophagy pathway that involves piecemeal degradation of mitochondrial proteins in a LC3C- and p62-dependent manner and contributes to mitochondrial homeostasis maintenance when cells rely on oxidative phosphorylation. | 10.1016/j.molcel.2017.10.029 |
pubmed_889_5579 | We report on the low-temperature scanning tunneling microscopy/spectroscopy (STM/STS) study of the (Bi, Na)/Si(1 1 1)[Formula: see text] reconstruction that is known to possess Fermi surface with apparently good nesting. We found that defects on this surface produce a one-dimensional-like pattern with the periodicity of 8.2 [Formula: see text] 0.4 [Formula: see text] that is incommensurate with the [Formula: see text] lattice period. The [Formula: see text] mapping analysis reveals an occurrence of the k-dependent branch associated with quasi-particle interference and the k-independent branch associated with the nesting vector connecting the parallel segments of the (Bi,Na)/Si(1 1 1)[Formula: see text] Fermi surface, the fingerprint of the charge-density-wave (CDW) phase. The STS data demonstrates that development of the CDW phase leads to reducing electron density of states at the Fermi level. | 10.1088/1361-648X/aaf9ea |
pubmed_101_11972 | Extreme precipitation events influence watershed, agriculture, and urban management. The probability of extreme precipitation is estimated for storm water management using precipitation intensity-duration-frequency (PIDF) curves. This study explores developing PIDF curves from dynamically downscaled 36- and 12-km simulations using the Weather Research and Forecasting (WRF) model. Three modeled data sets are examined: 36-km WRF model forced with 2.5° (~275-km) NCEP-DOE AMIP-II Reanalysis (R2); 36-km WRF model forced with 0.75° (~80-km) ERA-Interim; and 12-km WRF model forced with ERA-Interim. The WRF outputs are verified against historical observations for three cities in the Eastern United States using a 23-year period (1988-2010). The 36-km WRF data set driven by R2 produced PIDF curves that were acceptable at the 12- to 24-hr durations, but those WRF data could not realistically simulate extremes represented by the high-intensity, short-duration precipitation events. Increasing the resolution of WRF's driving data from R2 to ERA-Interim did not improve WRF's representation of precipitation events. Using 12-km grid spacing enhances WRF's ability to reproduce PIDF curves developed from observations. Finer grid spacing dramatically improves the frequency and intensity of the 1- to 3-hr events and improves the 6- to 24-hr events. However, improvements with the 12-km WRF data did not apply equally to all study sites, suggesting further modifications to the WRF configuration and/or methodology are necessary. Although imperfect, the results here lend confidence to using modeled data to construct PIDF curves, which could be valuable for projecting changes to parameters used in urban and environmental planning. | 10.1029/2019JD031584 |
pubmed_762_3325 | We aimed at investigating a new model of mild focal cerebral ischemia in rats with repeated, noninvasive magnetic resonance scanning combined with histology. Magnetic resonance imaging yielded information about infarct development enabling us to test the putative growth of the infarct over time. The effect of local temperature at the occlusion site in this model was furthermore tested. Thirty-three Wistar rats were subjected to 30 min of simultaneous common carotid artery and distal middle cerebral artery occlusion or sham treatment. Animals were magnetic resonance-scanned repeatedly between day one and day 14 after surgery, then sacrificed, and paraffin brain sections stained. All animals scanned 24 h after reperfusion showed an area of edema in the affected cortex, which later was identified as an infarct. Animals with a temperature of 33.9 +/- 1.5 degrees C at the MCA site (hypothermic) showed smaller infarcts (14.4 +/- 10 mm3) than animals with normothermic local temperature (36.7 +/- 0.2 degrees C, 57.7 +/- 26.4 mm3). Infarct size was maximal on day 3 after ischemia but decreased as edema subsided. Infarct volumes from histology and magnetic resonance imaging correlated well. The model reproducibly yielded cortical infarcts, which did not grow after edema had subsided. Local temperature had a considerable effect on final infarct size. | 10.1179/016164102101200898 |
pubmed_196_8926 | Natural resistance associated macrophage protein genes (Nramp) is one of the important candidate genes responsible for regulating immune response against pathogen infection. The aim of the present was to quantify expression of Nramp gene in response to pathogen infection. Here, a Nramp was identified and molecularly characterized from Pelteobagrus fulvidraco (PfNramp). The obtained 3134 bp cDNA fragment of PfNramp comprised a 5'-untranslated region (UTR) of 81 bp, a 3'-UTR of 1403 bp and an open reading frame (ORF) of 1650 bp, encoding a polypeptide of 549 amino acids that contained a typical structural features of Nramp domain (Pfam01566). BLAST analysis exhibited that PfNramp shared sequence similarity to other organisms, in particular to Ictalurus furcatus (92%), Danio rerio (82%), and Homo sapiens (77%). Phylogenetic analysis revealed that PfNramp is close to Teleostei. Real-time quantitative reverse transcription-PCR (qRT-PCR) analysis showed that PfNramp was expressed in all examined tissues, with the highest abundance in liver. The mRNA expression of PfNramp was remarkably increased at different time points after lipopolysaccharide (LPS), and polyriboinosinic polyribocytidylic acid (poly I:C) challenge. These results suggest that PfNramp is an inducible protein in the innate immune reactions of P. fulvidraco and probably in other fish species. | 10.1016/j.ijbiomac.2019.09.008 |
pubmed_238_26368 | Background
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy. An accurate diagnosis of ACC is of paramount importance as it greatly impacts the management and prognosis of a patient. However, the differentiation between early stage, low-grade ACC and adrenocortical adenoma (ACA) may not always be straightforward. The recommended classification system, namely, the Weiss scoring system, is not without flaws. We herein report two cases of ACC which were initially diagnosed as ACA according to the Weiss scoring system but developed distant metastases in subsequent years. Case Presentation. Case 1: A 60-year-old Chinese woman presented with a recent onset of worsening of blood pressure control and clinical features of Cushing's syndrome. Investigations confirmed ACTH-independent endogenous hypercortisolism, and a CT abdomen showed a 6 cm right adrenal mass. Twenty-four-hour urine steroid profiling revealed co-secretion of adrenal androgens and atypical steroid metabolites. Laparoscopic right adrenalectomy was performed, and pathology of the tumor was classified as an ACA by the Weiss scoring system. Four years later, the patient presented with an abrupt onset of severe hypercortisolism and was found to have a metastatic recurrence in the liver and peritoneum. The patient received a combination of mitotane, systemic chemotherapy, and palliative debulking surgery and succumbed 8.5 years after the initial presentation due to respiratory failure with extensive pulmonary metastases. Case 2: A 68-year-old Chinese woman presented with acute bilateral pulmonary embolism and was found to have a 3 cm left adrenal mass. Hormonal workup confirmed ACTH-independent endogenous hypercortisolism, and laparoscopic left adrenalectomy revealed an ACA according to the Weiss scoring system. Five years later, she presented with recurrent hypercortisolism due to hepatic and peritoneal metastases. The patient had progressive disease despite mitotane therapy and succumbed 7 years after initial presentation.
Conclusions
Although the Weiss scoring system is recommended as the reference pathological classification system to diagnose adrenocortical carcinoma, there remain tumors of borderline malignant potential which may escape accurate classification. Various alternative classification systems and algorithms exist but none are proven to be perfect. Clinicians should recognize the potential limitation of these histological criteria and scoring systems and incorporate other clinical parameters, such as the pattern of hormonal secretion, urinary steroid profiling, and radiographic features, to improve the prognostication and surveillance strategy of these tumors. | 10.1155/2022/7395050 |
pubmed_377_3088 | Simultaneous assessment of the spectroscopic absorption signal of gas enclosed in a scattering medium and the corresponding optical path length of the probing light is demonstrated using a single setup. Sensitive gas absorption measurements are performed by a tunable diode laser using wavelength-modulation spectroscopy, while the path length is evaluated by the frequency-modulated cw technique commonly used in the field of telecommunication. Proof-of-principle measurements are demonstrated with water vapor as the absorbing gas and using polystyrene foam as an inhomogeneously scattering medium. The combination of these techniques opens up new possibilities for straightforward evaluation of gas presence and exchange in scattering media. | 10.1364/OL.36.003036 |
pubmed_617_3628 | An inverted circadian rhythm of melatonin (MT) likely contributes to the sleep disturbance in patients with Smith-Magenis syndrome (SMS). Plasma MT levels have documented this altered rhythm, but daytime levels of salivary MT has not been determined. Daytime measures of salivary MT might have utility in home/outpatient settings for assessing MT levels in undiagnosed patients with clinical features of SMS. The objective of this study was to determine the utility of daytime salivary MT as a diagnostic test in SMS. Thirty individuals with confirmed SMS [28 with del 17p11.2 and 2 with the retinoic acid induced 1 (RAI1) gene mutation] and five controls were studied. Single or serial daytime salivary MT levels were measured. The mean midday salivary MT level was 79.0 pg/ml in SMS patients, compared with 16.3 pg/ml in controls, with nine patients having values similar to controls. The median MT level in SMS patients was 49.0 pg/ml (first and third quartile values = 15.5 and 106.8 pg/ml). Twenty-six (90%) of 29 patients had at least one MT value >15.5 pg/ml, including 70 (78%) of 90 samples from patients with del 17p11.2 and one (20%) of five samples from the two patients with the RAI1 mutation. Neither the pattern of medication use nor age had an effect on daytime salivary MT levels. Although most SMS patients had elevated daytime salivary MT levels, multiple sampling appears necessary to distinguish patients with SMS from other conditions. | 10.1002/ajmg.a.33158 |
pubmed_530_5661 | In an effort to increase the security of the supply chain for raw materials used in the manufacture of human therapeutics, a routine screen to detect the presence of adulteration using fully automated nuclear magnetic resonance spectroscopy has been developed and qualified for use in quality control laboratories. The method involves the collection of one-dimensional (1)H and (13)C spectra, which are subsequently processed to identify and quantitate raw material constituents by comparison to a spectral database. The resulting method is an easy-to-use limit test that can automatically determine the integrity of incoming raw materials. The method is intended to be used in good manufacturing practice production facilities and is suitable for excipients and aqueous soluble raw materials used in biopharmaceutical processes.
LAY ABSTRACT
In an effort to increase the security of the supply chain for raw materials used in the manufacture of human therapeutics, a routine screen to detect the presence of adulteration using fully automated nuclear magnetic resonance (NMR) spectroscopy has been developed and qualified for use in quality control laboratories. The method involves the collection of NMR spectra, which are subsequently processed to identify and quantitate raw material constituents by comparison to a spectral database. The resulting method is an easy-to-use limit test that can automatically determine the integrity of incoming raw materials. The method is intended to be used in good manufacturing practice production facilities and is suitable for excipients and aqueous soluble raw materials used in biopharmaceutical processes. | 10.5731/pdajpst.2012.00890 |
pubmed_532_17749 | Robert Weiss (1973) conceptualised loneliness as perceived social isolation, which he described as a gnawing, chronic disease without redeeming features. On the scale of everyday life, it is understandable how something as personally aversive as loneliness could be regarded as a blight on human existence. However, evolutionary time and evolutionary forces operate at such a different scale of organisation than we experience in everyday life that personal experience is not sufficient to understand the role of loneliness in human existence. Research over the past decade suggests a very different view of loneliness than suggested by personal experience, one in which loneliness serves a variety of adaptive functions in specific habitats. We review evidence on the heritability of loneliness and outline an evolutionary theory of loneliness, with an emphasis on its potential adaptive value in an evolutionary timescale. | 10.1080/02699931.2013.837379 |
pubmed_105_612 | Mitochondrial dysfunction is implicated in the pathogenesis of diabetic kidney disease (DKD). Compared to the vast body of evidence from preclinical in vitro and in vivo studies, evidence from human studies is limited. In a comprehensive search of the published literature, findings from studies that reported evidence of mitochondrial dysfunction in individuals with DKD were examined. Three electronic databases (PubMed, Embase, and Scopus) were searched in March 2022. A total of 1339 articles were identified, and 22 articles met the inclusion criteria. Compared to non-diabetic controls (NDC) and/or individuals with diabetes but without kidney disease (DC), individuals with DKD (age ~55 years; diabetes duration ~15 years) had evidence of mitochondrial dysfunction. Individuals with DKD had evidence of disrupted mitochondrial dynamics (11 of 11 articles), uncoupling (2 of 2 articles), oxidative damage (8 of 8 articles), decreased mitochondrial respiratory capacity (1 of 1 article), decreased mtDNA content (5 of 6 articles), and decreased antioxidant capacity (3 of 4 articles) compared to ND and/or DC. Neither diabetes nor glycemic control explained these findings, but rather presence and severity of DKD may better reflect degree of mitochondrial dysfunction in this population. Future clinical studies should include individuals closer to diagnosis of diabetes to ascertain whether mitochondrial dysfunction is implicated in the development of, or is a consequence of, DKD. | 10.3390/cells11162481 |
pubmed_38_44 | Most liquid chromatography (LC) mass spectrometric (MS) methods used for routine monitoring of lipophilic marine toxins focus on the analysis of the 13 toxins that are stated in European Union legislation. However, to date over 200 lipophilic marine toxins have been described in the literature. To fill this gap, a screening method using LC coupled to high resolution (HR) orbitrap MS (resolution 100000) for marine lipophilic toxins has been developed. The method can detect a wide variety of okadaic acid (OA), yessotoxin (YTX), azaspiracid (AZA) and pectenotoxin (PTX) group toxins. To build a library of toxins, shellfish and algae samples with various toxin profiles were obtained from Norway, Ireland, United Kingdom, Portugal and Italy. Each sample extract was analyzed with and without collision induced dissociation fragmentation. Based on their mass and specific fragmentation pattern, 85 different toxins were identified comprising 33 OA, 26 YTX, 18 AZA and 8 PTX group toxins. A major complication of full scan HRMS is the huge amount of data generated (file size), which restricts the possibility of a fast search. A software program called metAlign was used to reduce the orbitrap MS data files. The 200-fold reduced data files were screened using an additional software tool for metAlign: 'Search_LCMS'. A search library was constructed for the 85 identified toxins. The library contains information about compound name, accurate mass, mass deviation (<5 ppm), retention time (min) and retention time deviation (<0.2 min). An important feature is that the library can easily be exchanged with other instruments as the generated metAlign files are not brand-specific. The developed screening procedure was tested by analyzing a set of known positive and blank samples, processing them with metAlign and searching with Search_LCMS. A toxin profile was determined for each of the contaminated samples. No toxins were found in the blank sample, which is in line with the results obtained for this sample in the routine monitoring program (rat bioassay and tandem LC-MS). | 10.1016/j.aca.2010.11.036 |
pubmed_150_8610 | BACKGROUND
Endothelial dysfunction associated with hypercholesterolemia is an early event in atherosclerosis characterized by redox imbalance associated with high superoxide production and reduced nitric oxide (NO) and hydrogen peroxide (H2O2) production. Aerobic exercise training (AET) has been demonstrated to ameliorate atherosclerotic lesions and oxidative stress in advanced atherosclerosis. However, whether AET protects against the early mechanisms of endothelial dysfunction in familial hypercholesterolemia remains unclear. This study investigated the effects of AET on endothelial dysfunction and vascular redox status in the aortas of LDL receptor knockout mice (LDLr(-/-)), a genetic model of familial hypercholesterolemia.
METHODS
Twelve-week-old C57BL/6J (WT) and LDLr(-/-) mice were divided into sedentary and exercised (AET on a treadmill 1 h/5 × per week) groups for 4 weeks. Changes in lipid profiles, endothelial function, and aortic NO, H2O2 and superoxide production were examined.
RESULTS
Total cholesterol and triglycerides were increased in sedentary and exercised LDLr(-/-) mice. Endothelium-dependent relaxation induced by acetylcholine was impaired in aortas of sedentary LDLr(-/-) mice but not in the exercised group. Inhibition of NO synthase (NOS) activity or H2O2 decomposition by catalase abolished the differences in the acetylcholine response between the animals. No changes were noted in the relaxation response induced by NO donor sodium nitroprusside or H2O2. Neuronal NOS expression and endothelial NOS phosphorylation (Ser1177), as well as NO and H2O2 production, were reduced in aortas of sedentary LDLr(-/-) mice and restored by AET. Incubation with apocynin increased acetylcholine-induced relaxation in sedentary, but not exercised LDLr(-/-) mice, suggesting a minor participation of NADPH oxidase in the endothelium-dependent relaxation after AET. Consistent with these findings, Nox2 expression and superoxide production were reduced in the aortas of exercised compared to sedentary LDLr(-/-) mice. Furthermore, the aortas of sedentary LDLr(-/-) mice showed reduced expression of superoxide dismutase (SOD) isoforms and minor participation of Cu/Zn-dependent SODs in acetylcholine-induced, endothelium-dependent relaxation, abnormalities that were partially attenuated in exercised LDLr(-/-) mice.
CONCLUSION
The data gathered by this study suggest AET as a potential non-pharmacological therapy in the prevention of very early endothelial dysfunction and redox imbalance in familial hypercholesterolemia via increases in NO bioavailability and H2O2 production. | 10.1186/s12967-016-0972-z |
pubmed_386_9442 | BACKGROUND
Single-stage breast reconstruction following skin-sparing or nipple-sparing mastectomy with free deep inferior epigastric perforator (DIEP) flap usually does not require a large skin paddle. Most of the flap skin paddle is removed, and the flap is placed under native, conserved skin to provide adequate volume to the reconstructed breast mound. We hypothesized that conservation of intact dermis and its subdermal plexus has a critical role in overall flap perfusion through recruitment of indirect linking vessels. The study goal was to investigate and compare the vascularity of DIEP flaps with intact dermis versus DIEP flaps with the dermis removed.
METHODS
Twelve hemi-DIEP flaps were harvested from fresh cadavers. The largest dominant perforator was cannulated using a 24-gauge butterfly catheter. Flaps were imaged with computed tomography (CT) after injection of a contrast agent. After scanning, the contrast agent was flushed out of the flap. The flap skin was removed with cautery at the subdermal dissection plane. The flaps were reimaged with CT after injection of the contrast agent. Three-dimensional (3-D) CT angiographic reconstructions were obtained for each protocol stage, and the percentage of flap perfusion was calculated. Flap vascularity with and without dermis was compared.
RESULTS
A mean difference of 25.9% in flap perfusion occurred when the dermis was removed (P < 0.001). The 3-D CT angiographic images showed that the impact of dermis excision was caused by interrupting the recurrent flow through the dermis and subdermal plexus via indirect linking vessels.
CONCLUSION
The dermis has a significant role in enhancing overall DIEP flap perfusion through preservation of indirect linking vessels organized in the subdermal plexus. Despite being time consuming, a cautious de-epithelialization of the DIEP flap should be performed to retain dermis integrity. Enhancement of flap vascularity ultimately leads to a decrease in such complications as partial or total flap necrosis, as well as fat necrosis. | pubmed_386_9442 |
pubmed_167_1012 | One of the major challenges in chemical synthesis is the selective oxyfunctionalization of non-activated C-H bonds, which can be enabled by biocatalysis using cytochrome P450 monooxygenases. In this study, we report on the characterization of the versatile CYP109Q5 from Chondromyces apiculatus DSM436, which is able to functionalize a wide range of substrates (terpenes, steroids and drugs), including the ring of β-ionone in non-allylic positions. The crystal structure of CYP109Q5 revealed flexibility within the active site pocket that permitted the accommodation of bulky substrates, and enabled a structure-guided approach to engineering the enzyme. Some variants of CYP109Q5 displayed a switch in selectivity towards the non-allylic positions of β-ionone, allowing the simultaneous production of 2- and 3-hydroxy-β-ionone, which are chemically challenging to synthesize and are important precursors for carotenoid synthesis. An efficient whole-cell system finally enabled the production of up to 0.5 g l-1 hydroxylated products of β-ionone; this system can be applied to product identification in further biotransformations. Overall, CYP109Q5 proved to be highly evolvable and active. The studies in this work demonstrate that, using rational mutagenesis, the highly versatile CYP109Q5 generalist can be progressively evolved to be an industrially valuable specialist for the synthesis of specific products. | 10.1111/1751-7915.13354 |
pubmed_915_18433 | Colonic intussusception caused by benign tumour in adults is uncommon condition. Lipoma as benign tumour arises from submucosal layer of gastrointestinal tract and derives from mature adypocytes. It is usually small asymptomatic lesion and reveals during colonoscopy, CT, surgery or autopsy accidentally. However, in cases with large size it may cause abdominal pain, constipation, diarrhoea, anaemia, bleeding or intussusceptions. We present a 52-year-old female patient with colonic intussusception caused by lipoma of the transverse colon and with congenital dolichocolon. The patient had several episodes of bowel obstructions which were treated conservatively. We performed elective open extended right hemicolectomy, ileotransversostomy end-to-end. | 10.1136/bcr-2019-230732 |
pubmed_271_322 | The activities of single step sol-gel made calcium oxide on alumina catalysts were studied as a function of CaO loading, methanol/oil molar ratio and the amount of the catalyst in the transesterification of sunflower oil at 50°C. Also, the turnover frequency (TOF) of the catalysts was calculated to better understand the relationship between the basicity/basic strength and the catalytic activity. From volcano curve (TOF vs. basic strength), it was found that under 50°C and methanol/oil molar ratio of 9, 60% CaO/Al(2)O(3) had the highest turnover frequency, 0.028s(-1), whereas 85% CaO/Al(2)O(3) showed the highest biodiesel yield, ∼96.6%, but TOF obtained on it was 0.012s(-1). It seemed that 60% CaO catalyst had the proper basic strength to obtain the highest TOF. | 10.1016/j.biortech.2011.11.135 |
pubmed_321_5543 | BACKGROUND
Post-stroke depression (PSD) seriously affects the rehabilitation of nerve function and quality of life. However, the pathogenesis of PSD is still not clear. This study aimed to investigate the demographic, clinical, and biochemical factors in patients with PSD.
METHODS
Patients with an acute ischemic stroke, who met the inclusion criteria at Shanghai Tenth People's Hospital from April 2016 to September 2016, were recruited for this study. The stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS), and the mental state was assessed using Mini-Mental State Examination (MMSE), Hamilton Depression Scale (HAMD), and Hamilton Anxiety Scale (HAMA) at 1 week of admission. The patients were divided into PSD and non-PSD groups. The demographic and clinical characteristics, as well as the biochemical factors, were compared between the two groups. A logistic regression analysis was performed to identify the risk factors for depression following stroke.
RESULTS
A total of 83 patients with acute ischemic stroke were recruited. Of these, 36 (43.4%) developed depression. The multivariate logistic regression analysis indicated that high NIHSS [odds ratio (OR): 1.84, 95% confidence interval (CI): 1.09-3.12, P = 0.023] and high HAMD scores (OR: 2.38, 95% CI: 1.61-3.50, P < 0.001) were independent risk predictors for PSD and so were lower dopamine level (OR: 0.64, 95% CI: 0.45-0.91, P = 0.014), lower 5-hydroxytryptamine level (OR: 0.99, 95% CI: 0.98-1.00, P = 0.046), higher tumor necrosis factor-α level (OR: 1.05, 95% CI: 1.00-1.09, P = 0.044), and lower nerve growth factor level (OR: 0.06, 95% CI: 0.01-0.67, P = 0.022).
CONCLUSIONS
The identification of higher NIHSS scores, higher HAMD scores, lower dopamine level, lower 5-hydroxytryptamine level, higher tumor necrosis factor-α level, and lower nerve growth factor level might be useful for clinicians in recognizing and treating depression in patients after a stroke. | 10.1186/s12883-017-0980-5 |
pubmed_1029_15449 | One of the major reasons for the existence of National Institute of Mental Health's Intramural Research Program is the study of schizophrenia. The program provides relatively stable funding for the long-term examination of the basic and clinical sciences as they relate to this major public-health problem. This article and those that follow review some of the past and current contributions to our understanding of schizophrenia that have emanated from the Intramural Research Program. | 10.1093/schbul/14.2.145 |
pubmed_1_13765 | With the particular conjugation structure in the heme prosthetic group, Cyt c shows unusual functions similar to chlorophyll while irradiated by specific wavelength of UV-Vis lights. To further reveal mechanism of the photo-irradiation of Cyt c, we then studied various external factors that may influence the photo induced process. The absorbance intensity increase of band (317 nm) and Q band (520 nm and 549 nm)indicated Cyt c in phosphate-buffered saline within N2 atmosphere was photoreduced to Fe(II) Cyt c. Irradiated by 410 nm, the photoreduction process was facilitated by Met. But Trp, Tyr and Phe impeded the process due to their light absorbance abilities. In addition, the results of fluorescence and CD spectra indicated that the microenvironment polarity of Trp residue varied during the photoreduction process. And the secondary structure of Cyt c changed with lower α-helix/βsheet ratio. The photoreduction mechanism of Cyt c was intramolecular electron transfer and porphyrin cation radicals were generated. The protein structure of Cyt c changed as well as part of the photoreduction. | 10.2174/0929866522666150707115231 |
pubmed_531_15782 | A new, Swedish case with Tay or IBIDS syndrome is presented. The boy had growth and mental retardation, congenital ichthyosis and brittle hair. He was the only child in an uncle-niece marriage. The boy suffered recurrent infections and died at the age of 3 years from pneumonia. Clinical data on 15 cases are presented from a study of the literature. | 10.1111/j.1651-2227.1991.tb11817.x |
pubmed_248_14993 | OBJECTIVE
To investigate the effects of losartan, a specific angiotensin II receptor blocker, on slowing progression of renal insufficiency in patients with biopsy-proven chronic allograft nephropathy (CAN) and the molecular mechanism of the therapy.
METHODS
Twenty-two renal transplant recipients with biopsy-proven CAN (group A) were treated with losartan within two months after renal dysfunction for at least one year. Losartan was administered at a dose of 50 mg/d. Twenty-four recipients in the same fashion (group B) who never received angiotensin II receptor antagonist were studied as control. The investigation time for each patient lasted one year. Renal functions and concentrations of plasma and urine transforming growth factor-beta1 (TGF-beta1) were compared between the two groups at the initiation and end of the study. In group A, expressions of TGF-betal mRNA and immunofluorescence intensity of TGF-betal protein and pathological alterations in renal biopsy specimens were compared between before losartan therapy and after one year of the therapy.
RESULTS
At the initiation of the investigation, no significant differences were found between group A and group B in clinical data such as donor age, cold-ischemia time, HLA mismatch, levels of creatinine clearance (Ccr), plasma and urine TGF-beta1 concentrations. One year later, 14 of 22 (63.6%) patients showed stable or improved graft functions in group A, and 4 of 24 (16.7%) in group B. The difference was significant (P < 0.05). At the end of the study, urine TGF-betal concentration was 273.8 +/- 84.1 pg/mg x Cr in group A and 457.2 +/- 78.9 pg/mg x Cr in group B. During one year study period, loss of Ccr was 6.6 +/- 5.4 mL/min in group A and 16.2 +/- 9.1 mL/min in group B. Both of the differences were significant between the two groups (P < 0.01). No significant differences were found in plasma TGF-betal concentrations between the four values determined at the initiation and end of the study in the two groups (F = 2.56, P > 0.05). After one year losartan therapy, group A showed a significant decrease in expressions of TGF-beta1 mRNA and TGF-betal protein in renal biopsy specimens [from 1.59 +/- 0.35 to 0.96 +/- 0.27 and from (10.83 +/- 2.33) x l0(6) to (6.41 +/- 1.53) x 10(6), respectively; both P < 0.01], but in light microscopy the histological changes were similar to the first renal biopsy. Losartan was excellently tolerated in all patients in group A. No cases with losartan therapy showed too low blood pressure and other side effects.
CONCLUSION
This study suggests that losartan have an effect on slowing progression of CAN. Reducing production of intrarenal TGF-betal may play a decisive role in the efficacy of losartan. | pubmed_248_14993 |
pubmed_527_14403 | The role of cartilage canals is to transport nutrients and biological factors that cause the appearance of the secondary ossification centre (SOC). The SOC appears in the centre of the epiphysis of long bones. The canal development is a complex interaction between mechanical and biological factors that guide its expansion into the centre of the epiphysis. This article introduces the 'Hypothesis on the growth of cartilage canals'. Here, we have considered that the development of these canals is an essential event for the appearance of SOC. Moreover, it is also considered to be important for the transport of molecular factors (RUNX2 and MMP9) at the ends of such canals. Once the canals are merged in the centre of the epiphysis, these factors are released causing hypertrophy of adjacent cells. This RUNX2 and MMP9 release occurs due to the action of mechanical loads that supports the epiphysis. In order to test this hypothesis, we use a hybrid approach using the finite element method to simulate the mechanical stresses present in the epiphysis and the cellular automata to simulate the expansion of the canals and the hypertrophy factors pathway. By using this hybrid approach, we have obtained as a result the spatial-temporal patterns for the growth of cartilage canals and hypertrophy factors within the epiphysis. The model is in qualitative agreement with experimental results previously reported by other authors. Thus, we conclude that this model may be used as a methodological basis to present a complete mathematical model of the processes involved in epiphyseal development. | 10.1080/10255841003606116 |
pubmed_51_10307 | This article provides a comprehensive review of spine segmentation and enumeration. This important and relatively underappreciated issue, when neglected, frequently results in confusion in vertebral numbering and ultimately may result in wrong segment interventions. The authors supplement this topic with a discussion of normal variants. | 10.1016/j.rcl.2012.04.003 |
pubmed_501_5995 | Meibomian carcinoma is rare but carries a grave prognosis. The lesion may be easily mistaken for inflammatory condition. Therefore, any nodular or recurrent lesion on the eyelid of an elderly person should be examined histologically. A case is presented in which the tumor was successfully treated by the Mohs microscopically controlled excision. | 10.1016/s0190-9622(80)80185-x |
pubmed_630_7471 | BACKGROUND & AIMS
Several hepatitis B virus (HBV) markers have been identified as factors associated with the development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We clarified the predictive power of HBV markers for the development of HCC using receiver operating characteristic (ROC) analysis with a consideration of time dependence.
METHODS
A total of 1031 CHB patients who were not treated with nucleos(t)ide analogue therapy were enrolled. Univariate, multivariate, and time-dependent ROC curves for HBV markers associated with the development of HCC were analyzed.
RESULTS
Seventy-eight patients developed HCC during the follow-up period (median duration 10.7years). Different levels or statuses of several HBV markers (HBV genotype, HBV DNA, HBV core-related antigen (HBcrAg), hepatitis B e antigen (HBeAg), and basal core promoter (BCP)), but not hepatitis B surface antigen, were significantly associated with the incidence of HCC by univariate analysis using the log-rank test. Cox proportional hazards models using the covariates of HBV genotype status, HBV DNA levels, HBcrAg levels, HBeAg status, and BCP status indicated that HBcrAg >2.9logU/ml (hazard ratio (HR), 5.05; 95% confidence interval (CI), 2.40-10.63) and BCP mutation (HR, 28.85; 95% CI, 4.00-208.20) were independently associated with the incidence of HCC. Additionally, time-dependent ROC analysis showed that HBcrAg was superior to HBV DNA in terms of predictive power for HCC development throughout the follow-up period.
CONCLUSIONS
Elevation of HBcrAg levels in CHB patients is associated with the development of HCC. HBcrAg is an excellent predictor of HCC development.
LAY SUMMARY
Hepatitis B virus (HBV) core-related antigen (HBcrAg) is an excellent predictor of hepatocellular carcinoma (HCC) development in chronic hepatitis B patients without nucleos(t)ide analogue therapy. HBcrAg was superior to HBV DNA in terms of predictive power for HCC development by time-dependent receiver operating characteristic analysis. | 10.1016/j.jhep.2016.03.013 |
pubmed_134_1484 | The effects of dietary supplementation of L-carnosine (beta-alanyl-L-histidine) on ischemia/reperfusion-induced acute renal failure (ARF) in rats were examined. Ischemic ARF was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal functional parameters such as blood urea nitrogen, plasma creatinine, creatinine clearance, urine flow, urinary osmolality and fractional excretion of sodium were measured. Renal function in ARF rats markedly decreased at 1 d after reperfusion. Prior feeding of L-carnosine-containing diet (0.0001 w/w%) for 2 weeks attenuated the ischemia/reperfusion-induced renal dysfunction. Histopathological examination of the kidney of ARF rats revealed severe renal damages, such as tubular necrosis, proteinaceous casts in tubuli and medullary congestion, which were also significantly suppressed by the dietary supplementation of L-carnosine. These findings strongly suggest that L-carnosine supplementation is useful as a prophylactic treatment in the development of the ischemic ARF. | 10.1248/bpb.28.361 |
pubmed_761_21287 | A redox-responsive supramolecular nanocarrier was constructed from the self-assembly of spermine modified cyclodextrin and oxaliplatin prodrug. The nanocarrier could preferentially accumulate in polyamine transporter over-expressing HCT116 cells, releasing drugs under a reducing intracellular environment to maximize anticancer treatment. | 10.1039/c8cc07858k |
pubmed_78_3654 | BACKGROUND
In the SHOCK trial, the group of patients aged >or=75 years did not appear to derive the mortality benefit from early revascularization (ERV) versus initial medical stabilization (IMS) that was seen in patients aged <75 years. We sought to determine the reason for this finding by examining the baseline characteristics and outcomes of the 2 treatment groups by age.
METHODS
Patients with cardiogenic shock (CS) secondary to left ventricular (LV) failure were randomized to ERV within 6 hours or to a period of IMS. We compared the characteristics by treatment group of patients aged >or=75 years and of their younger counterparts.
RESULTS
Of the 56 enrolled patients aged >or=75 years, those assigned to ERV had lower LV ejection fraction at baseline than IMS-assigned patients (27.5% +/- 12.7% vs 35.6% +/- 11.6%, P = .051). In the elderly ERV and IMS groups, 54.2% and 31.3%, respectively, were women ( P = .105) and 62.5% and 40.6%, respectively, had an anterior infarction (P = .177). The 30-day mortality rate in the ERV group was 75.0% in patients aged >or=75 years and 41.4% in those aged <75 years. In the IMS group, 30-day mortality was 53.1% for those aged >or=75 years, similar to the 56.8% for patients aged <75 years.
CONCLUSIONS
Overall, the elderly randomized to ERV did not have better survival than elderly IMS patients. Despite the strong association of age and death post-CS, elderly patients assigned to IMS had a 30-day mortality rate similar to that of IMS patients aged <75 years, suggesting that this was a lower-risk group with more favorable baseline characteristics. The lack of apparent benefit from ERV in elderly patients in the SHOCK trial may thus be due to differences in important baseline characteristics, specifically LV function, and play of chance arising from the small sample size. Therefore, the SHOCK trial overall finding of a 12-month survival benefit for ERV should be viewed as applicable to all patients, including those >or=75 years of age, with acute myocardial infarction complicated by CS. | 10.1016/j.ahj.2005.03.045 |
pubmed_764_2816 | The organization and evolution of insect societies has amazed natural historians since Aristotle. Charles Darwin considered social insects to be a major difficulty for his theory of evolution by natural selection because they demonstrate a rich diversity of adaptation among sterile workers leading to a complex division of labour, something that should not occur if variation in individual reproductive success is the grist for the mill of natural selection. This article shows how division of labour can self-organize from groups of cohabiting individuals without the necessity of a past history of natural selection for co-operative behaviour. It then explores how more complex social systems may evolve. | 10.1016/s0160-9327(97)80220-7 |
pubmed_920_654 | BACKGROUND
Radicular low back pain is difficult to treat and commonly encountered in the Emergency Department (ED). Pain associated with acute radiculopathy results in limited ability to work, function, and enjoy life, and is associated with increased risk of chronic opioid therapy. In this case report, we describe the first ED-delivered ultrasound-guided caudal epidural steroid injection (ESI) used to treat medication-refractory lumbar radiculopathy, which resulted in immediate and sustained resolution of pain.
CASE REPORT
A 56-year old man with a past medical history of chronic lumbar radiculopathy presented to the ED with acute low back and right lower-extremity pain. Based on history and physical examination, a right L5 radiculopathy was suspected. His pain was poorly controlled despite multimodal analgesia, at which point he was offered admission or an ultrasound-guided caudal ESI. The procedure was performed using dexamethasone, preservative-free normal saline, and preservative-free 1% lidocaine solution, after which the patient reported 100% resolution of his pain and requested discharge from the ED. Why Should an Emergency Physician Be Aware of This? The safety and efficacy of ultrasound-guided caudal ESIs have been established, but there is a paucity of literature exploring their application in the ED. We present a case of a refractory lumbar radiculopathy successfully treated with an ultrasound-guided caudal ESI. ED-performed epidurals can be one additional tool in the emergency physician arsenal to treat acute or chronic lumbar radiculopathy. | 10.1016/j.jemermed.2021.04.015 |
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