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pubmed_316_8070 | An intravenous infusion of platelet activating factor (Paf) in the guinea-pig elicits an increase in bronchial responsiveness to the spasmogens, histamine and bombesin. Airways obstruction induced by bombesin in Paf-treated animals is poorly reversed by isoprenaline compared to comparable airways obstruction induced by bombesin in vehicle-treated animals. Isoprenaline induced a comparable dose-related relaxation in vitro of tracheal smooth muscle isolated from Paf- and vehicle-treated animals. No change in beta-adrenoceptor numbers or binding affinity was observed in lungs removed from Paf-treated animals in comparison with those from vehicle-treated animals, or after direct incubation with Paf in vitro. The reduced bronchodilator responsiveness to isoprenaline in Paf-treated animals is not related to changes in pulmonary beta-adrenoceptor function. These results suggest that non-spasmogenic elements may contribute to airways obstruction induced in hyper-responsive animals. | 10.1111/j.1476-5381.1987.tb11224.x |
pubmed_1054_4570 | 336 estimations of circulating immune complexes have been performed on the sera of blood donors by four different methods: the solid phase C1q binding test, the fluid phase C1q binding assay, the conglutinin binding test and the Raji cell radio-immune assay. Between 68 and 105 subjects were used in the analysis of each method. With the first three methods, immune complex levels showed a peaked asymmetric distribution with a positive tail including about 10% of subjects, whereas using the fourth method immune complex values were widely spread. No difference in immune complex values between males and females was found. There was a significant trend for the prevalence of immune complexes to increase with age when methods were used which detect complexes through C3 binding. In a further 13 subjects tested at regular intervals during a period of 24 hours, using the fluid phase C1q binding test, significant variations in immune complex levels were found but no consistent pattern of variation at different hours of the day or after meals could be seen. In studies of immune complexes on small groups of patients it is advisable to test multiple samples from te same subjects taken at different times, whereas when large series of patients are being studied results should be compared to those obtained with age matched controls. | pubmed_1054_4570 |
pubmed_242_22912 | It is highly desirable to develop controlled synthetic methods at low temperature (<100 °C) for defined phases of titanium oxide nanoparticle. We present here a simple low temperature approach which is based on the peroxide route. This approach allows the preparation of phase-pure rutile and anatase without the use of any additives or surfactants or external acids. The formation of crystalline phases is found to be dependent on reaction temperature and highly dependent on concentration. Phase-pure rutile is obtained in two concentration zones while phase-pure anatase is obtained in one concentration zone. The relationship between phases and reaction conditions (concentration and temperature) fits well with the nucleation diffusion rate model. | pubmed_242_22912 |
pubmed_111_16640 | Rat hepatic fatty acid binding protein (hFABP) may play an important role in the intracellular transport and metabolism of fatty acids. Recent reports have suggested a substantial circadian variation in the amount of hFABP in liver, and a half-life of less than 2 h for this protein has been inferred. In the present study, the kinetics of hFABP turnover were examined directly. hFABP half-life measured after pulse labeling with NaH14CO3 was 3.1 days compared with 2.9 days for total cytosol protein. Following double-isotope labeling, the charge isoforms of hFABP showed similar rates of turnover, all of which were slower relative to whole cytosol protein turnover. Following a 48-h fast, total liver hFABP measured by immunoassay fell 65%, paralleling a 60% fall in total cytosol protein. Refeeding for 24 h did not lead to a significant recovery of either hFABP or total cytosol protein content. No significant change was observed in hFABP abundance between mid-light and mid-dark periods of a 24-h light-dark cycle. These studies showed that hFABP has a relatively slow rate of turnover and that it is not acutely modulated by dietary or diurnal influences. | pubmed_111_16640 |
pubmed_546_9835 | A Comprehensive review of quantitative structure-activity relationship (QSAR) studies on antiarrhythmic agents is presented. From the discussion point of view, the antiarrhythmic agents have been put into two broad classes: specific and nonspecific. While the main members of the former class can be beta-adrenergic blocking agents (beta-blockers), any chemical that can act directly on the myocardial cell membrane, producing a cardiodepressant effect via changes in basic electrophysiological properties of the membrane, such as automaticity, excitability, conductivity, and refractoriness, has been put in the latter class. QSARs exhibit that the biological actions of a variety of drugs belonging to any class depend primarily on the lipophilic haracter of the molecule or substituents. Thus, the hydrophobic interaction is found to play a dominant role in the action of antiarrhythmic agents. In certain cases, the QSARs also exhibit the role of electronic parameters, suggesting that certain receptors may have electronic site also, permitting the drugs to involve in some electronic interactions, too. | pubmed_546_9835 |
pubmed_669_20073 | Perovskite-based multijunction solar cells are a potentially cost-effective technology that can help surpass the efficiency limits of single-junction devices. However, both mixed-halide wide-bandgap perovskites and lead-tin narrow-bandgap perovskites suffer from non-radiative recombination due to the formation of bulk traps and interfacial recombination centers which limit the open-circuit voltage of sub-cells and consequently of the integrated tandem. Additionally, the complex optical stack in a multijunction solar cell can lead to losses stemming from parasitic absorption and reflection of incident light which aggravates the current mismatch between sub-cells, thereby limiting the short-circuit current density of the tandem. Here, an integrated all-perovskite tandem solar cell is presented that uses surface passivation strategies to reduce non-radiative recombination at the perovskite-fullerene interfaces, yielding a high open-circuit voltage. By using optically benign transparent electrode and charge-transport layers, absorption in the narrow-bandgap sub-cell is improved, leading to an improvement in current-matching between sub-cells. Collectively, these strategies allow the development of a monolithic tandem solar cell exhibiting a power-conversion efficiency of over 23%. | 10.1002/adma.202110053 |
pubmed_564_6587 | PURPOSE
To assess the frequency of splenic vein thrombosis (SVT) after splenectomy and its consequences on patient treatment.
MATERIALS AND METHODS
A group of 183 consecutive patients who underwent splenectomy were evaluated. Of these patients, 119 underwent postoperative ultrasound (US) or computed tomography.
RESULTS
SVT was diagnosed in 13 of 119 patients in the first 2 weeks after surgery. In these 13 patients, splenectomy had been performed for hematologic disorders (n = 12) or trauma (n = 1). Seven of the 13 patients were asymptomatic. After anticoagulant therapy, follow-up US of 12 patients showed resolution of thrombosis with no complications in 10 patients; two patients developed cavernous transformation of the portal vein.
CONCLUSION
Since only 65% of patients underwent imaging, the true frequency of SVT could not be determined; however, it occurred in at least 7% of patients who underwent splenectomy. Routine Doppler US should be performed after splenectomy to allow early anticoagulant therapy in patients with SVT. | 10.1148/radiology.190.1.8259430 |
pubmed_93_15260 | A library of new aryl-substituted naphthalene C8-linked pyrrolo[2,1-c][1,4]benzodiazepine (PBD) conjugates with various linker architectures were designed, synthesized, and evaluated for their anticancer activity against a panel of 11 human cancer cell lines. All 32 conjugates show anticancer potential, with some of them exhibiting particularly high activity (0.01-0.19 μM). Thermal denaturation studies showed effective DNA binding capacity relative to DC-81. In assays for biological activity relating to cell-cycle distribution, these PBD conjugates induce G₀/G₁-phase arrest and also cause an increase in the levels of p53 and caspase-9 proteins, followed by apoptotic cell death. One conjugate in particular is the most promising candidate of the series, with the potential to be selected for further studies, either alone or in combination with existing anticancer therapies. | 10.1002/cmdc.201100207 |
pubmed_546_15964 | BACKGROUND
Impairment of intestinal barrier function occurs under a variety of inflammatory conditions and is mediated at least in part by interferon gamma (IFN-gamma) induced nitric oxide (NO) production. Previous in vivo studies have shown that systemic lipopolysaccharide treatment caused an induction of the rat inducible nitric oxide synthase (iNOS) mRNA primarily in villus cells, rather than in undifferentiated crypt cells.
AIMS
To examine iNOS induction by IFN-gamma in vitro as a function of enterocyte differentiation.
METHODS
Preconfluent and postconfluent Caco-2 cells were treated with IFN-gamma in the presence or absence of various inhibitors. Northern analyses were performed to assess the magnitude of iNOS mRNA induction. IFN-gamma receptor mRNA and protein levels were determined.
RESULTS
iNOS mRNA induction by IFN-gamma occurred at two hours and was not blocked by cycloheximide, indicating that it is an immediate early response. iNOS induction and nitrite/nitrate increases were inhibited by dexamethasone and pyrrolidine dithiocarbamate, supporting an important role for the NF-kappaB transcription factor in this process. The stimulated iNOS induction was seen almost exclusively under conditions of cellular differentiation-that is, in postconfluent Caco-2 cells. This increased IFN-gamma responsiveness seen in postconfluent Caco-2 cells correlated with an increased expression of IFN-gamma receptor, whereas T84 and HT-29 cells did not show any significant alterations in either iNOS induction or IFN-gamma receptor levels as a function of postconfluent growth.
CONCLUSIONS
With regard to iNOS mRNA induction, IFN-gamma responsiveness is acquired during Caco-2 cell differentiation, perhaps related to an increase in the numbers of IFN-gamma receptors. | 10.1136/gut.44.5.659 |
pubmed_41_25506 | Direct Z-scheme NiTiO3/g-C3N4 heterojunctions were successfully assembled by using simple calcination method and the photoelectrochemical and photocatalytic performance were investigated by light emitting diode (LED). The photoanode composed by the heterojunction with about 50 wt % NiTiO3 content exhibits the best photoelectrochemical activity with photoconversion efficiency up to 0.066%, which is 4.4 and 3.13 times larger than NiTiO3 or g-C3N4. The remarkably enhanced photoelectrochemical and photocatalytic activity of the heterojunction can be due to the efficiently photogenerated electron-hole separation by a Z-scheme mechanism. | 10.1021/acsami.7b12386 |
pubmed_191_18078 | OBJECTIVE
The study used a rat model of moderate protein restriction exclusively during fetal and early neonatal life, which has been established to cause intrauterine early growth retardation, to investigate possible association between adipocyte glucose utilisation and leptin secretion in vivo.
DESIGN
These rats, termed early protein restricted, were transferred to a diet containing the standard amount of protein at weaning and remained on this diet til adulthood, at which time adipocyte glucose utilisation and leptin secretion was compared with that of age-matched controls. Insulin status was modulated by acute (2 h) insulin infusion at a constant rate (4.2 mU/min per kg) to elevate insulin to the high physiological range. Euglycaemia was maintained by variable glucose infusion.
MEASUREMENTS
Glucose utilisation was measured in vivo in conscious unrestrained rats using 2-deoxy[1-3H] glucose. Leptin concentrations (measured by radioimmunoassay) and whole-body glucose kinetics (measured using [3-3H] glucose) were studied in the postabsorptive state and after acute insulin stimulation.
RESULTS
Adipose-tissue glucose utilisation rates in vivo tended to be higher in the post-absorptive state and were consistently 1.8-3.0-fold higher after insulin stimulation in the early-protein-restricted group compared with the control group. Both the absolute increase in leptin concentration elicited by hyperinsulinaemia and the magnitude of the effect of insulin to elevate plasma leptin levels were greater in the early-protein-restricted group compared with the control group (by 2.2-fold and 1.6-fold, respectively). The effect of insulin to stimulate R(d) was much greater in the early-protein-restricted group (4.1-fold) than in the control group (2.2-fold) and the absolute increase in R(d) elicited by insulin was 43% higher in the early-protein-restricted group than in the control group.
CONCLUSIONS
It is concluded that poor early growth enhances the acute leptin response to changes in insulin status through programmed changes in adipocyte glucose handling. | 10.1038/sj.ijo.0801836 |
pubmed_455_22952 | The use of the 2-point seat belt or lap belt in motor vehicles, particularly to restrain young rear seat passengers, remains an issue of some concern. The occurrence of lumbar spinal flexion-distraction injuries in lap belt restrained children and adolescents during road traffic accidents is a well known phenomenon, but is still occurring. High velocity paediatric Chance fractures are frequently associated with significant intra-abdominal trauma. We present the case of a Chance fracture sustained by a 15 year old girl, involved in a motor vehicle collision, while wearing a lap belt. We emphasise the need to develop safer seat belt designs for juvenile car passengers. | pubmed_455_22952 |
pubmed_1030_19380 | Evidence from the literature suggests an association between Dupuytren disease and frozen shoulder syndrome, both clinically and histologically. An increased tendency for fibrotic healing after repetitive microtrauma could be an underlying mechanism. However, it remains unclear how strong this association is and if only mild signs of Dupuytren disease would also increase the risk of frozen shoulder. In 61 patients, we examined the hands for signs of Dupuytren disease and the shoulders for pain and limited motion. We found a 21,7% prevalence of frozen shoulder syndrome in patients with signs of Dupuytren disease versus 13,9% in those without. The other way around, in patients with frozen shoulder syndrome the prevalence of Dupuytren disease was 50% versus 36.7% in those without frozen shoulder syndrome. These differences were not statistically significant, contrary to similar research in the literature. However, methodological issues, especially the choice of control group, may explain the differences between our findings and previous studies. We conclude that the clinical association between Dupuytren disease may not be so strong as previously thought, especially in patients with only limited signs of the disease. | 10.52628/88.2.9933 |
pubmed_701_20719 | Vitamin D is responsible, through the actions of its metabolite, 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25-(OH)2D3], for the generation of a wide array of biological responses, particularly in the intestine, kidney, and bone. 1 alpha,25-(OH)2D3 is known to interact with its nuclear receptor to mediate the regulation of gene transcription. Although many genes and gene products have been shown to be regulated by 1 alpha,25-(OH)2D3 (e.g. calbindin-D28K in the intestine and kidney; collagen, osteocalcin,and osteopontin in bone), their recognition has been largely the result of empirical testing. In this report we have used subtractive hybridization analysis of complementary DNA libraries prepared from messenger RNA (mRNA) isolated from the intestine and kidney of vitamin D-replete or vitamin D-deficient chicks to identify genes for novel proteins whose steady state mRNA levels are regulated by dietary vitamin D status. In the kidney we observed the down-regulated expression of at least seven mitochondrially encoded transcripts and the up-regulated expression of five nuclear encoded genes, two of which are metallothionein and the beta-subunit of aldolase. In the intestine, six mitochondrially encoded transcripts are up-regulated, and seven nuclear encoded transcripts were either up- or down-regulated. Thus, in addition to identifying new nuclear encoded genes whose mRNAs are regulated by vitamin D status, our approach has demonstrated the tissue-specific regulation of mitochondrial gene expression in the intestine and kidney. | 10.1210/endo.136.12.7588303 |
pubmed_1030_4475 | The practical electrosynthesis of hydrogen peroxide (H2O2) is hindered by the lack of inexpensive and efficient catalysts for the two-electron oxygen reduction reaction (2e- ORR) in neutral electrolytes. Here, we show that Ni3HAB2 (HAB = hexaaminobenzene), a two-dimensional metal organic framework (MOF), is a selective and active 2e- ORR catalyst in buffered neutral electrolytes with a linker-based redox feature that dynamically affects the ORR behaviors. Rotating ring-disk electrode measurements reveal that Ni3HAB2 has high selectivity for 2e- ORR (>80% at 0.6 V vs RHE) but lower Faradaic efficiency due to this linker redox process. Operando X-ray absorption spectroscopy measurements reveal that under argon gas the charging of the organic linkers causes a dynamic Ni oxidation state, but in O2-saturated conditions, the electronic and physical structures of Ni3HAB2 change little and oxygen-containing species strongly adsorb at potentials more cathodic than the reduction potential of the organic linker (Eredox ∼ 0.3 V vs RHE). We hypothesize that a primary 2e- ORR mechanism occurs directly on the organic linkers (rather than the Ni) when E > Eredox, but when E < Eredox, H2O2 production can also occur through Ni-mediated linker discharge. By operating the bulk electrosynthesis at a low overpotential (0.4 V vs RHE), up to 662 ppm of H2O2 can be produced in a buffered neutral solution in an H-cell due to minimized strong adsorption of oxygenates. This work demonstrates the potential of conductive MOF catalysts for 2e- ORR and the importance of understanding catalytic active sites under electrochemical operation. | 10.1021/jacs.2c06810 |
pubmed_748_15714 | A patient with the genetic condition neurofibromatosis type I and no known coagulopathy undergoing cesarean delivery, had diffuse uterine and surgical site bleeding that was not correctable by oxytocin, methylergonovine and PGF2 alpha. Despite good uterine tone, hemorrhage continued from the uterus and the surrounding tissues, persisting even after surgical ligation of the uterine arteries. With no change in her condition, which was behaving clinically as a coagulopathy, an infusion of desmopressin acetate (DDAVP) was begun. The patient's bleeding promptly resolved shortly after infusion of this agent. A review of relevant literature suggests that platelet reactivity of patients with neurofibromatosis type 1 is attenuated in some in vitro conditions. Thus, there may be some theoretical basis for using DDAVP in patients with neurofibromatosis type 1 who have bleeding problems with no other known source, such as in the case presented here. | 10.1016/j.ijoa.2004.01.008 |
pubmed_24_19712 | Neutrophil activates and injures tissues and organs during sepsis or septic shock. Blood purification therapies such as continuous veno-venous hemofiltration (CVVH) and direct hemoperfusion with polymyxin-immobilized fiber (PMX-DHP) have been used for the treatment of sepsis and septic shock, however, the effects of such therapies on neutrophil activation have previously been poorly understood. We sought to evaluate neutrophil reactive oxygen species (ROS), especially H2O2 production, in the pathophysiology of sepsis or septic shock and the effect of CVVH or PMX-DHP on neutrophil ROS. Seven critically ill septic patients requiring CVVH (and 12 matched septic patients who did not require CVVH as control) and seven septic shock patients treated with PMX-DHP were studied. We found that patients with sepsis or septic shock had significantly higher levels of neutrophil ROS compared with normal volunteers (183 +/- 42, 292 +/- 90, and 103 +/- 30) (P < 0.05, and < 0.005). Neutrophil ROS did not change over time in patients treated either with CVVH or without CVVH. In contrast, neutrophil ROS significantly inhibited PMX-DHP treatment in patients with septic shock (pretreatment; 292 +/- 88 vs. post-treatment; 205 +/- 93, P < 0.05). In conclusion, neutrophil ROS was significantly enhanced in the sepsis or septic shock affected patients. CVVH did not affect neutrophil ROS while PMX-DHP significant inhibited neutrophil ROS. | 10.1111/j.1744-9987.2006.00339.x |
pubmed_100_10525 | Transcriptional factor nuclear factor-kappaB (NF-κB) plays a crucial role in human breast cancer cell invasion and metastasis. The carboxyl terminus of Hsc70-interacting protein (CHIP) is a U-box-type ubiquitin ligase that induces ubiquitination and proteasomal degradation of its substrate proteins. In this study, we investigated the role of CHIP in the NF-κB pathway in the invasion of MDA-MB-231 cells, a highly aggressive breast cancer cell line. We showed that overexpression of CHIP significantly inhibits the invasion of the MDA-MB-231 cells. The overexpression of CHIP suppressed expression of urokinase plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9) in MDA-MB-231 cells. Moreover, CHIP strongly inhibited the nuclear localization and the transcriptional activity of NF-κB. The activation of the IkappaB kinase complex (IKK) was also blocked by CHIP overexpression. Importantly, CHIP overexpression resulted in a significant decrease in the level of TNF receptor-associated factor 2 (TRAF2), an upstream key player in the NF-κB pathway. However, the level of TRAF2 was restored after treatment with a proteasome inhibitor, MG-132. Moreover, CHIP overexpression promoted the ubiquitination of TRAF2. We also found cell invasion significantly decreased in cells transfected with TRAF2 small interfering RNA (siRNA). In contrast, when CHIP expression was suppressed by siRNA in poorly invasive MCF-7 cells, cell invasion significantly increased in conjunction with enhanced NF-κB activation and TRAF2 levels. Taken together, these results suggest that CHIP regulates NF-κB-mediated cell invasion via the down-regulation of TRAF2. | 10.1002/jcb.23292 |
pubmed_327_1665 | The present review summarizes the up-to-date knowledge on the sexual dimorphism of the CNS with special regard to the sexual differentiation of the bed nucleus of the stria terminalis (BST) and the amygdala in rat. The authors provide new evidence for the sexual dimorphism and differentiation of GABAergic, leucine-enkephalin-containing and parvalbumin-immunoreactive neurons in the BST and the amygdala of the rat. Together with testing the gender differences, age-related changes in numbers of the neuronal subpopulations, mentioned above are followed. The authors' results provide morphological and immunocytochemical data that may be used for further studies on sexually dimorphic circuitry and its functional significance. | 10.1007/978-3-642-57269-2 |
pubmed_1082_4659 | These studies were designed to compare the effects of nitric oxide (NO) generating compounds with those of several iron containing compounds which do not generate NO on glutamate receptor function. Stimulation of primary cultures of cerebellar granule cells with N-methyl-D-aspartate (NMDA) or kainate results in the elevation of intracellular calcium ([Ca2+]i) and cGMP and the release of glutamate. The iron containing compounds, sodium nitroprusside (SNP), potassium ferrocyanide (K4Fe(CN)6) and potassium ferricyanide (K3Fe(CN)6) decrease the NMDA-induced release of glutamate. SNP is the only compound of the above 3 agents which generates NO. A non-iron, NO generating compound, S-nitroso-N-acetylpenicillamin (SNAP), has no effect on the NMDA-induced glutamate release. Potassium ferrocyanide (Fe II), but not potassium ferricyanide (Fe III), blocks NMDA-induced cGMP elevations after 3 min exposure times. This contrasts with the NO generating compounds (both SNP and SNAP) which elevate cGMP levels. Furthermore, both potassium ferrocyanide (Fe II) and SNP (Fe II) suppress the elevation of [Ca2+]i induced by NMDA but neither potassium ferricyanide (Fe III) nor SNAP are effective in this regard. These effects are also independent of cyanide as another Fe II compound, ferrous sulfate (FeSO4) is also able to suppress NMDA-induced elevations of [Ca2+]i. SNP was unable to suppress kainate receptor functions. Collectively, these results indicate that Fe II, independently of NO, has effects on NMDA receptor function. | 10.1007/BF00969689 |
pubmed_384_557 | Exposure of procaryotic and eucaryotic cells to mutagenic agents generally gives both complete mutants and mosaic mutants. Irradiation of the eucaryotic multicellular alga Ulva mutabilis with ultraviolet light has given exclusively complete mutants. | 10.1126/science.168.3933.843 |
pubmed_585_14189 | Situs inversus totalis (SIT) is an uncommon anomaly characterised by transposition of organs to the opposite side of the body in a mirror image of normal. It may cause difficulties in the diagnostic and therapeutic management of abdominal pathology due to the mirror-image anatomy. We report the management of a case of symptomatic cholilithiasis with emphasis on its surgical technique. | 10.12816/0003097 |
pubmed_263_15323 | Power frequency magnetic fields (PFMF) have been reported to affect several cellular functions, such as cell proliferation and apoptosis. In this study, we investigated the effects of PFMF on mouse embryonic fibroblasts (MEF) autophagy. After cells were exposed to 50 Hz PFMF at 2 mT for 0.5 h, 2 h, 6 h, 12 h, and 24 h, we observed a significant increase in autophagic markers at 6 h, including (i) higher microtubule-associated protein 1 light chain 3-II (LC3-II), (ii) the increased formation of GFP-LC3 puncta, and (iii) increased numbers of autophagic vacuoles under transmission electron microscope. Moreover, we provide convincing evidence using chloroquine (CQ) that the increase of autophagic markers was the result of enhanced autophagic flux and not the suppression of lysosomal function. In a search for molecular mechanisms underlying PFMF-mediated autophagy, we observe that the autophagic process involved reactive oxygen species (ROS) and was independent of the mammalian target of rapamycin (mTOR) signaling pathway. | pubmed_263_15323 |
pubmed_1123_12650 | Racial/ethnic diversity has become an increasingly important variable in the social sciences. Research from multiple disciplines consistently demonstrates the tremendous impact of ethnic diversity on individuals and organizations. Investigators use a variety of measures, and their choices can affect the conclusions that can be drawn and limit the ability to compare and generalize results across studies effectively. The current article reviews 3 popular approaches to the measurement of diversity: the simplistic majority-minority approach and 2 multiple categories variants, the generalized variance and the lesser used entropy statistic. We discuss the properties of each approach and reject the majority-minority approach. We provide 5 examples using the generalized variance and entropy statistics and illustrate their versatility and flexibility. We urge investigators to adopt these multicategory measures and to use our discussion to determine which measure of diversity is most appropriate given the nature of one's data set and research question. | 10.1037/a0027129 |
pubmed_970_11165 | OBJECTIVES
This study aimed to evaluate data on early diagnosis and therapeutic management of rudimentary horn pregnancy (RHP).
MATERIAL AND METHODS
Patients diagnosed with RHP at a tertiary center between for two periods of 2008-2012 and 2013-2018 were analysed retrospectively. We obtained information of patients from hospital electronic archive registration system. Data on demographic characteristics, clinical presentation, gestational age at presentation, presenting symptoms, diagnostic methods, and therapeutic management were noted and analysed by descriptive statistical method. Demographic datas, the complaint of patient's admission to hospital, history of cesarean section, preliminary diagnosis and intraoperative diagnosis were compared between periods of 2008-2012 and 2013-2018.
RESULTS
A total of 14 RHP patients were included. Eight (57.1%) of these patients were diagnosed between 2008-2012 (Group 1), whereas six patients (42.9%) were diagnosed between 2013-2018 (Group 2). Rudimentary horn was non-communicating in 13 patients (92.8%). Communicated form was observed in 1 patient in group 1. RHP was diagnosed on the left side in nine patients (64.2%). Six of these patients were observed in group 1 and 3 were in group 2. The pre-rupture diagnosis was made in 10 (71.4%) patients. Six (100%) of 10 patients were in group 2. In addition, in group 1, four patients (50%) experienced intraoperative RHP rupture. RHP was diagnosed before rupture in 2 (33.3%) patients in group 2.
CONCLUSIONS
It is an indication of advanced ultrasonographic technology as well as increased carefulness on the physician side and raised alertness on the patient side that today both RHP and preoperative rupture of RHP are less frequent. Still, further awareness is required among physicians of the necessity of excision of a rudimentary horn that is detected at the time of C-section. | 10.5603/GP.2020.0027 |
pubmed_34_2687 | Recent studies regard bone marrow stromal cells as a potential andidate for cellular therapy of traumatic brain injury and thus as an attractive alternative for embryonic and fetal stem cells. Numerous experiments indicate that bone marrow stromal cells play an important role in the repair of injured brain tissue and also support healing processes. Findings of in vitro and in vivo studies show that these cells have an ability to differentiate into cells of multiple tissues, including neurons and glial cells and to secrete an array of growth factors and cytokines, which have an influence on repair of damaged tissue. In addition, treatment of traumatic brain injury with bone marrow stromal cells promotes functional recovery of injured animals. Taking this into consideration, there is hope for using bone marrow stromal cells in brain injury therapy, which is very difficult because of specific events that occur in the pathological conditions. However, mechanisms responsible for the observed therapeutic potential of bone marrow stromal cells still remain unclear. The review presents achievements in studies on bone marrow stromal cells as a source of therapeutic benefits in treatment of traumatic brain injury and addresses the question of their possible future use in clinical trials. | pubmed_34_2687 |
pubmed_1118_4787 | This study examined the relationship between extracurricular physical activity (PA) levels and students' motivational and emotional experience during physical education (PE) classes and how this psychological experience can predict the intention to be physically active. The sample consisted of 811 Spanish secondary education students (371 boys and 440 girls) aged between 11 and 17 years (M = 13.15, SD = 1.16). Students completed questionnaires about their PA levels, their intention to be physically active, and their motivational and emotional experience during PE classes. A cluster analysis was used to classify the students according to their level of extracurricular PA. Based on a regression analysis, the variables enjoyment, pride, hopelessness, competence, satisfaction, and autonomous motivation played the highest role, predicting the intention to be physically active in the future. Statistical differences were found among the different PA profiles in these variables during the PE classes (MANCOVA). In conclusion, hours of PA outside school have a high relationship with the students' emotional and motivational experience in their PE classes, which is related with the intention to practise PA in the future. A series of strategies have been proposed at both the institutional level and the teacher level to improve the PE psychological experience of those students who practise less extracurricular PA. | 10.3390/ijerph19159539 |
pubmed_1051_18510 | With the further transformation of The Large Sky Area Multi-Object Fiber Spectroscopic Telescope, the new generation of fiber positioner robot chooses a 4 mm hollow cup motor with minimum phase inductance. Because the load of the fiber positioner robot is constant and the inertia of the motor is very small, an open loop positioning control method based on Space Vector Pulse Width Modulation is proposed, and the specific open loop parameters are directly tuned by relevant experimental strategies. The critical factors of the open loop driving mode are discussed in detail from four aspects: subdivision, fundamental frequency, wave generation mode and peak current. Based on the actual fiber positioner robot, the hardware driver and assessment platform are built. The positioning tests show that the method proposed is practical and effective, and meets the precision positioning demand of the new generation optical fiber positioner robot. | 10.1038/s41598-022-06214-7 |
pubmed_339_23424 | The native form of tyrosine hydroxylase (TH) is a homotetramer which consists of four identical subunits each with an MW of approximately 60 kD. The relationships between the catalytic activity of TH and oligomerization of the enzyme have not yet been characterized. We have investigated, by deletion and/or substitution mutagenesis, the involvement of the leucine zipper (LZ) motifs in the oligomer formation of TH and its relation to catalytic activity. Our results demonstrate that deletion of the carboxyl-terminal LZ (LZ-C) abolishes tetramer formation. Interruption of the other two LZ motifs (LZ-A and LZ-B), located in a central region of the catalytic domain by substitution of Leu to Pro at residues 294 and 301 or 386 and 393 has no effect on the tetramer formation of TH. However, the interruption of LZ-A and LZ-B abolishes TH enzymatic activity. The substitution of Leu residues 188 and 190 with Pro at the regulatory domain of TH reduces enzymatic TH activity without affecting tetramer formation. Thus, LZ-C is required for tetramer formation, while LZ-A and LZ-B seem to be involved in the catalytic activity without affecting the tetramer formation of TH. Copyright 1996 S. Karger AG, Basel | 10.1007/BF02257963 |
pubmed_560_9061 | INTRODUCTION
An increase in ethical conflicts is being observed in the modern intensive care setting, as more complex therapeutic strategies are available and the treatment of old and very old patients is integrated into the clinical routine due to changes in medical options and social epidemiology. Physicians, nurses and families need ethical support to come to a decision about medical treatment when value conflicts are involved.
METHODS
The basis of medical ethics is reported followed by a presentation of personal experiences and a reference overview regarding the impact of ethics consultations.
RESULTS
Common ethical conflicts in the intensive care setting result from the lack of precise knowledge on patient preferences and due the use of modern "high-tech" intensive care medicine the prognosis of recovery and quality of life of (old) patients seems to be difficult to assess. Ethical definitions of treatment perspectives will find an important and increasing place in intensive care competence in the future, although currently there is a lack of theoretical and practical instruction in ethics. The goal of ethics consultations is to help physicians, nurses and family members by a structuration of the problem and by a moderation of discussion and problem resolution including a special ethical workflow. Ethics consultations seem to be useful in resolving conflicts that may inappropriately prolong unwanted treatment.
CONCLUSIONS
The increase of the incidence of ethical conflicts in the intensive care setting may impact ethics consultations which help the integration of ethical principles into the clinical practice. | 10.1007/s00101-011-1976-y |
pubmed_36_14759 | Cardiovascular toxicity is a potential complication of cancer chemotherapy (CC) that increases the morbidity and mortality of cancer patients. Cardiac arrhythmias have been reported as an adverse effect of many chemotherapeutic drugs, including novel targeted therapies. The relationship between chemotherapy and arrhythmias has not been well-established and the proarrhythmogenic mechanisms remain uncertain as they can be the result of a direct electrophysiological effect or of changes in cardiac structure and function, including myocardial ischaemia and heart failure, which create an arrhythmogenic substrate. In this review we summarise available evidence of proarrhythmia induced by CC, discuss the possible mechanisms involved in this adverse effect and emphasise the importance of cardiac monitoring for the early diagnosis, intervention and surveillance of those patients more susceptible to develop proarrhythmia in an attempt to reduce the morbidity and mortality. Oncologists should be fully aware of proarrhythmia and the close collaboration between cardiologists and oncologists would result in a better cardiovascular assessment, risk stratification, cardiac monitoring and treatment during CC and during the follow-up. The final objective is to understand the mechanisms of proarrhythmia and evaluate its real incidence and clinical relevance so as to select the safest and most effective treatment for cancer patients. | 10.1007/s40264-014-0258-4 |
pubmed_425_19507 | The rise of academic clinical education programs underlines the growing influence of faculty development on how health care is taught and therefore practiced. Research to date has outlined the rapid rise of these postgraduate qualifications and their impact on their graduates' professional identities. Given the scale and nature of the change, it is worth considering these programs from a broader perspective. "Axes of difference" are invoked to chart the tensions and intersections between various social identities that form distinctive features of clinical education. Six axes are described: patients-clinicians, trainees-trainers, classrooms-clinics, uniprofessional-interprofessional, local-global, and teachers-clinicians. These reveal a range of complexities about faculty development, which can inform both practice and scholarship agendas. | 10.1097/CEH.0000000000000269 |
pubmed_143_17383 | Models for the ordered multiple categorical (OMC) response variable have already been extensively established and widely applied, but few studies have investigated linear regression problems with OMC predictors, especially in high-dimensional situations. In such settings, the pseudocategories of the discrete variable and other irrelevant explanatory variables need to be automatically selected. This paper introduces a transformation method of dummy variables for such OMC predictors, an L1 penalty regression method is proposed based on the transformation. Model selection consistency of the proposed method is derived under some common assumptions for high-dimensional situation. Both simulation studies and real data analysis present good performance of this method, showing its wide applicability in relevant regression analysis. | 10.1002/sim.8400 |
pubmed_495_10982 | An insoluble macromolecular Sn(II)(R-Sn) complex which strongly binds Sn(II) by chelation was applied to the direct 99mTc labeling of human immunoglobulin(IgG) to minimize the influence of Sn(II). 99mTc labeling was achieved at greater than 90% yield simply by the short-term mixing of IgGa containing > 2-SH groups per IgG molecule, 99mTc pertechnetate, and the R-Sn complex in pH 7 solution. The 99mTc-IgGa obtained by this labeling method has high stability based on the thiol-specific binding of 99mTc without transchelation from another weakly bound 99mTc-complex. | 10.1016/0969-8051(95)00012-m |
pubmed_528_6878 | The reproductive organs of some plants self-heat, release scent, and attract pollinators. The relations among these processes are not well understood, especially in the more ancient, nonflowering gymnosperm lineages. We describe the influence of plant volatiles in an obligate pollination mutualism between an Australian Macrozamia cycad (a gymnosperm with male and female individuals) and its specialist thrips pollinator, Cycadothrips chadwicki. Pollen-laden thrips leave male cycad cones en masse during the daily thermogenic phase, when cone temperatures and volatile emissions increase dramatically and thrips are repelled. As thermogenesis declines, total volatile emissions diminish and cones attract thrips, resulting in pollination of female cones. Behavioral and electrophysiological tests on thrips reveal that variations in b-myrcene and ocimene emissions by male and female cones are sufficient to explain the observed sequential thrips' repellence (push) and attraction (pull). These dynamic interactions represent complex adaptations that enhance the likelihood of pollination and may reflect an intermediate state in the evolution of biotic pollination. | 10.1126/science.1145147 |
pubmed_658_8150 | Ciprofloxacin distribution was assessed in cerebral tissues in 14 patients undergoing craniotomy. The study objective was to determine the brain tissue/serum concentration ratio of ciprofloxacin. Patients received a single intravenous (iv) 200 mg dose of ciprofloxacin. Mean (+/- S.D.) tissue/serum concentration ratios were (mg/kg): parietal fat during opening 1.40 +/- 1.05, during closure 1.34 +/- 1.17, in the dura mater 2.26 +/- 1.36, in skull bone during opening 0.44 +/- 0.29, during closure 0.97 +/- 1.57 and in brain tissue 0.88 +/- 0.99. Mean (+/- S.D.) concentrations of ciprofloxacin in brain tissue were 0.87 +/- 0.08 mg/kg, suggesting that a dose >200 mg iv ciprofloxacin is required to ensure therapeutic concentrations in brain tissue. | 10.1093/jac/dkf179 |
pubmed_72_4551 | BACKGROUND
Endoscopic ultrasound-guided fine needle aspiration is highly accurate for the diagnosis of malignancies surrounding the gastrointestinal tract. There is a lack of information on the usefulness of this technique in the diagnosis of colorectal cancer recurrence.
OBJECTIVE
The purpose of this work was to investigate the performance characteristics of endoscopic ultrasound-guided fine needle aspiration for the cytologic diagnosis of perirectal recurrence of colorectal cancer.
DESIGN
This was a retrospective study on the clinical and radiologic suspicion of perirectal recurrence of colorectal cancer.
SETTINGS
The study was conducted at 4 tertiary hospitals.
PATIENTS
Consecutive patients with suspicion of perirectal recurrence of colorectal cancer undergoing endoscopic ultrasound-guided fine needle aspiration between 2000 and 2013 were included in this study.
INTERVENTIONS
The study intervention was endoscopic ultrasound-guided fine needle aspiration.
MAIN OUTCOME MEASURES
Endoscopic ultrasound-guided fine needle aspiration performance characteristics and outcome (malignant or benign) were analyzed. The gold standard was cytologic results if malignancy or follow-up if benignity.
RESULTS
A total of 58 patients were included (32 men; mean age, 64.2 ± 10.0 years [range, 44-88 years]). The location of the initial neoplasm was the rectum for 42 patients and the colon for 16 patients. Endoscopic ultrasound findings included a mass in the anastomosis (n = 8), perirectal fat (n = 23), lymph nodes (n = 20), or asymmetric thickness of the rectal wall (n = 6). Cytology showed malignancy in 38 patients (67%), benign features in 17 (30%), and was not evaluable in 2. Mean follow-up to confirm a benign outcome was 51.3 ± 30.3 months (range, 5.2-180.0 months). Final outcome was recurrence in 40 patients (69%) and benignity in 18 patients (31%). Performance characteristics of endoscopic ultrasound-guided fine needle aspiration were sensitivity (97%), specificity (100%), positive predictive value (100%), negative predictive value (94%), and accuracy (98%). In the intention to diagnose analysis, the corresponding values were 95%, 100%, 100%, 90%, and 96%.
LIMITATIONS
This was a retrospective series with a limited number of patients.
CONCLUSIONS
Endoscopic ultrasound-guided fine needle aspiration is a highly accurate tool for the cytologic diagnosis of perirectal recurrence in patients with previous colorectal cancer. | 10.1097/DCR.0000000000000329 |
pubmed_726_20979 | Organ printing is a novel concept recently introduced in developing artificial three-dimensional organs to bridge the gap between transplantation needs and organ shortage. One of the major challenges is inclusion of blood-vessellike channels between layers to support cell viability, postprinting functionality in terms of nutrient transport, and waste removal. In this research, we developed a novel and effective method to print tubular channels encapsulating cells in alginate to mimic the natural vascular system. An experimental investigation into the influence on cartilage progenitor cell (CPCs) survival, and the function of printing parameters during and after the printing process were presented. CPC functionality was evaluated by checking tissue-specific genetic marker expression and extracellular matrix production. Our results demonstrated the capability of direct fabrication of cell-laden tubular channels by our newly designed coaxial nozzle assembly and revealed that the bioprinting process could induce quantifiable cell death due to changes in dispensing pressure, coaxial nozzle geometry, and biomaterial concentration. Cells were able to recover during incubation, as well as to undergo differentiation with high-level cartilage-associated gene expression. These findings may not only help optimize our system but also can be applied to biomanufacturing of 3D functional cellular tissue engineering constructs for various organ systems. | 10.1115/1.4024575 |
pubmed_468_5959 | INTRODUCTION
Many studies have found that positron emission tomography-computed tomography (PET-CT) has a high sensitivity and specificity in the identification of metastasis in cervical cancer. Herlev Hospital, Denmark, has been performing PET-CTs in stage I-IV cervical cancer since 1 May 2006. The present study investigates the positive (PPV) and negative predictive value (NPV) of PET-CT in stage I disease and the clinical impact of the scan results in all disease stages.
MATERIAL AND METHODS
In this retrospective study, 83 consecutive patients with cervical cancer were included between 1 May 2006 and 1 November 2007. Data were collected from patient records and PET-CT reports.
RESULTS
Among 47 stage I patients, four had PET-positive findings on the scan in addition to cervical cancer. Only one was a true positive finding. Pelvic lymphadenectomy was performed in 36 stage Ia2-Ib1 patients. Histology from stage I patients revealed a PPV of 25% and a NPV of 88%. Among a total of 36 stage II-IV patients, 14 had PET-positive findings. Five patients had a biopsy performed. Three of these patients were true positives and two were true negatives. Taking of biopsies in the remaining patients was clinically irrelevant. Five patients (6%), all in stage ≥ IIb, were offered an alternative treatment owing to the additional information obtained from the PET-CT.
CONCLUSION
PET-CT is useful in the identification of metastatic disease in cervical cancer and it may assist optimal treatment planning; especially in International Federation of Gynecologists & Obstetricians (FIGO) stage > I cancers. Histological verification of PET-positive findings is necessary. The clinical value of PET-CT in early stage cervical cancer may be questioned. | pubmed_468_5959 |
pubmed_1075_20052 | Fosfomycin is a wide-spectrum antibiotic that is used clinically to treat acute cystitis in the United States. The compound is produced by several strains of streptomycetes and pseudomonads. We sequenced the biosynthetic gene cluster responsible for fosfomycin production in Pseudomonas syringae PB-5123. Surprisingly, the biosynthetic pathway in this organism is very different from that in Streptomyces fradiae and Streptomyces wedmorensis. The pathways share the first and last steps, involving conversion of phosphoenolpyruvate to phosphonopyruvate (PnPy) and 2-hydroxypropylphosphonate (2-HPP) to fosfomycin, respectively, but the enzymes converting PnPy to 2-HPP are different. The genome of P. syringae PB-5123 lacks a gene encoding the PnPy decarboxylase found in the Streptomyces strains. Instead, it contains a gene coding for a citrate synthase-like enzyme, Psf2, homologous to the proteins that add an acetyl group to PnPy in the biosynthesis of FR-900098 and phosphinothricin. Heterologous expression and purification of Psf2 followed by activity assays confirmed the proposed activity of Psf2. Furthermore, heterologous production of fosfomycin in Pseudomonas aeruginosa from a fosmid encoding the fosfomycin biosynthetic cluster from P. syringae PB-5123 confirmed that the gene cluster is functional. Therefore, two different pathways have evolved to produce this highly potent antimicrobial agent. | 10.1128/AAC.06478-11 |
pubmed_629_475 | Mind-body medicine (MBM) as a holistic approach to health and healing has been shaped by research into stress physiology and stress psychology, by psychoneuro(endocrino)immunology and by Antonovsky's salutogenetic paradigm. MBM seeks to acknowledge physical, psychological as well as social and spiritual aspects of human beings. MBM constitutes one of the traditions, which the emerging field of integrative medicine in Germany draws upon, others being mainstream medicine, traditional European naturopathy and non-European methods like traditional Chinese medicine. The article outlines historical aspects of MBM, gives a brief review of research evidence, and introduces clinical MBM institutes in Germany. Especially the Clinic and Chair of Complementary and Integrative Medicine, Alfried Krupp von Bohlen und Halbach Foundation at the University Duisburg-Essen has been integrating MBM into the concept of integrative medicine. Considering that a growing number of health issues arises due to maladaptive lifestyles, MBM is being identified as a development that supports a shift from increasingly expensive treatments to more cost-effective preventive approaches. | 10.1007/s00103-006-0001-0 |
pubmed_359_17895 | Drosophila has been shown to be a valuable model for the investigation of host-pathogen interactions. Study of the Drosophila immune response has been hampered, however, by the lack of true Drosophila pathogens. In nearly all studies reported, the bacteria used were directly injected within the body cavity of the insect, bypassing the initial steps of a natural interaction. Here, we report the identification of a previously uncharacterized bacterial species, Pseudomonas entomophila (Pe), which has the capacity to induce the systemic expression of antimicrobial peptide genes in Drosophila after ingestion. In contrast to previously identified bacteria, Pe is highly pathogenic to both Drosophila larvae and adults, and its persistence in larvae leads to a massive destruction of gut cells. Using this strain, we have analyzed the modulation of the larval transcriptome upon bacterial infection. We found that natural infection by Pe induces a dramatic change in larval gene expression. In addition to immunity genes, our study identifies many genes associated with Pe pathogenesis that have been previously unreported. | 10.1073/pnas.0502240102 |
pubmed_2_22962 | The present study is designed to explore the mechanism of action of herbal formulation Lucer against experimentally induced gastric ulcers. The aqueous extract (120 and 180 mg/kg) of Lucer was tested against aspirin and ethanol-induced gastric ulcer model in rats. The drug has been found to be very effective in inhibiting gastric ulceration. This is evident from reduction in ulcer index parameters. Besides, significant reduction in acid secretory parameters such as total acidity, total acid output and volume of gastric secretion were also observed. It is concluded from this study that the drug possesses anti-ulcer activity in both the models. The anti-ulcer activity of the drug can be attributed to inhibition of acid secretary parameters and strengthening of gastric mucosal barrier. | 10.4103/0974-8520.105260 |
pubmed_507_14662 | The pathogenicity of a field isolate of Marek's disease virus (MDV) named GXY2 integrated with retroviral long terminal repeat (LTR) sequence from a chicken with MD tumors was evaluated. Experimental chickens were divided into group A, B, C, D and E. The later four groups were vaccinated on one-day-old with CVI988/Rispens for group B and D, with HVT for group C and E, while group A was taken as no-vaccinated control. On 8-day-old, group A, B and C were challenged with GXY2 by intra-abdominal injection, group D and E were kept as un-challenged control. All the birds were raised routinely until 82 days post-challenge (PC), died birds during the experiment and the slaughtered birds at the end of the experiment were necropsied and examined for gross lesions of MD and further confirmed by a developed polymerase chain reaction (PCR) based differential diagnosis technique for avian neoplastic diseases. The results showed that time of onset of MD death of group A, B and C were PC 25, 77 and 29 days with the incidences of visible MD visceral tumors. On PC 82 days, tumor incidences and mortalities of group A, B and C were 72%, 34.8% and 50%, 84%, 21.7% and 20%, respectively. The vaccination protection of CVI988/Rispense and HVT were 51.67% and 30.56% respectively. Among all the visceral organs, heart had the highest tumor incidences (23.5%), and then followed by liver (14.7%) and gizzard (10.3%). The weight-gain of unvaccinated birds was significantly depressed and severe dystrophy of thymus and bursa of Fabricius were also found. The results of the study demonstrated that isolate GXY2 possessed the ability of causing acute tumors and overcoming the protection of the vaccinations of either CVI988/Rispense or HVT. | pubmed_507_14662 |
pubmed_1111_10701 | Isotopic effects associated with molecular absorption are discussed with reference to natural phenomena including early solar system processes, Titan and terrestrial atmospheric chemistry, and Martian atmospheric evolution. Quantification of the physicochemical aspects of the excitation and dissociation processes may lead to enhanced understanding of these environments. Here we examine a physical basis for an additional isotope effect during photolysis of molecular nitrogen due to the coupling of valence and Rydberg excited states. The origin of this isotope effect is shown to be the coupling of diabatic electronic states of different bonding nature that occurs after the excitation of these states. This coupling is characteristic of energy regimes where two or more excited states are nearly crossing or osculating. A signature of the resultant isotope effect is a window of rapid variation in the otherwise smooth distribution of oscillator strengths vs. frequency. The reference for the discussion is the numerical solution of the time dependent Schrödinger equation for both the electronic and nuclear modes with the light field included as part of the Hamiltonian. Pumping is to all extreme UV dipole-allowed, valence and Rydberg, excited states of N(2). The computed absorption spectra are convoluted with the solar spectrum to demonstrate the importance of including this isotope effect in planetary, interstellar molecular cloud, and nebular photochemical models. It is suggested that accidental resonance with strong discrete lines in the solar spectrum such as the CIII line at 97.703 nm can also have a marked effect. | 10.1073/pnas.1102767108 |
pubmed_470_4601 | The t complex region of mouse chromosome 17 contains genetic information critical for embryonic development. To identify and map loci required for normal embryogenesis, a set of overlapping deletions (D17Aus9(df10J), D17Aus9(df12J), and D17Aus9(df13J)) surrounding the D17Aus9 locus and one encompassing the T locus, Del(17)T(7J), were bred in various combinations and the consequences of nullizygosity in overlapping regions were examined. The results indicated that there are at least two functional units within 1 cM of D17Aus9. l17J1 is a peri-implantation lethal mutation within the region deleted in D17Aus9(df13J), whereas l17J2 is a later-acting lethal defined by the region of overlap between Del(17)T(7J) and D17Aus9(df12J). Del(17)T(7J)/D17Aus9(df12J) embryos die around 10.5 dpc. The development of the mutant embryos is characterized by lack of axial rotation, an abnormal notochord structure, and a ballooning pericardium. These studies demonstrate the value of overlapping deletion complexes, as opposed to individual deletion complexes, for the identification, mapping, and analysis of genes required for embryonic development. | 10.1002/gene.10174 |
pubmed_990_18246 | This study investigated the effect of drinking tea or coffee on the lung cancer risk of male cigarette smokers in a case-control in Uruguay. Four hundred and twenty-seven lung cancer cases were frequency matched on age and residence with 428 hospitalized controls suffering from conditions unrelated to tobacco smoking and diet. Whereas coffee drinking had no effect on the lung cancer risk of the cigarette-smoking men in this study, black tea consumption decreased this risk. Heavy drinkers of tea (two or more cups of tea per day) were associated with a reduced risk of 0.34 (95% CI 0.14-0.84). This protective effect was more evident among Kreyberg I tumors (squamous cell and small cell) and among light smokers. Possible sources of bias and mechanisms of action are discussed. | 10.1016/s0169-5002(97)00075-5 |
pubmed_867_7822 | In this laboratory, a silicone chamber model for peripheral nerve regeneration in adult rats has been developed and used to define basic principles of the regenerative events, such as the sequential stages being followed during 'spontaneous' regeneration in vivo and the role of neuronotrophic- and neurite-promoting factors as well as extracellular matrix molecules. Each of the defined stages seems amenable to experimental modulation. Previous attempts to enhance regeneration included increasing the volume of the nerve chambers along with the modification of fibrin matrix formation by prefilling with saline (PBS) or matrix precursors. We present here the results of a series of experiments on the effects of exogenous biochemical agents applied by multiple injections into these in vivo chambers. Out of a variety of agents screened, a mixture of laminin (L), testosterone (T), ganglioside GM 1 (G), and catalase (C) was shown to advance substantially the progress of regeneration in 16 day chambers, as compared to PBS-prefilled and PBS-injected controls. LTGC-treatment at day 0, 6, and 10 postimplantation caused an increasingly frequent occurrence of cellular elements in cross-sections obtained from the middle (S5) of the chambers (i.e. 5 mm from the proximal stump), which was 2-fold for vessels, 3-fold for Schwann cells, and 10-fold for axons. When only sections containing axons 3 mm from the proximal stump (S3) were compared in experimental and control groups, computerized area measurements also revealed an average 2-fold difference for the cross-sectional size of the whole regenerate, the endoneurium and the space occupied by blood vessels. | 10.1016/0006-8993(87)91023-7 |
pubmed_177_24814 | Salecan is a novel water-soluble extracellular β-glucan and suitable for the hydrogel preparation due to its excellent physicochemical and biological properties. The present article describes the fabrication and characterization of a pH/magnetic field-driven hydrogel based on salecan-g-poly(vinylacetic acid-co-2-hydroxyethyl acrylate) [poly(VA-co-HEA)] copolymer and Fe3O4@Agarose nanoparticles for drug release testing. Vibrating sample magnetometer characterization verified that integration of Fe3O4@Agarose nanoparticles in the copolymer provided the sensitivity to magnetic fields. The doxorubicin hydrochloride (DOX) release test showed a pH/magnetic field-triggered and sustained release property, and the release could be accelerated under mildly acidic conditions or the presence of an external magnetic field. Meanwhile, the increase in salecan content could also enhance the release rate. Cytotoxicity assays revealed that the released DOX maintained relatively high killing efficacy of A549 cells. In sum, these salecan-g-poly(VA-co-HEA)/Fe3O4@Agarose hydrogels were well-suited for magnetically targeted drug delivery systems. | 10.1016/j.ijbiomac.2017.12.018 |
pubmed_1100_16162 | This paper reviews the newest advances in and opinions about cosmetic periodontal surgery. It includes a review of basic periodontal anatomy as it relates to restoring ideal health and esthetic gingival and osseous tissues. Treatments for excessive gingival tissue, ridge augmentations, and gingival deficiencies are discussed. These procedures are important in creating the illusion of a natural cosmetic smile in otherwise compromised situations. | pubmed_1100_16162 |
pubmed_1038_3408 | The Slump Test is an inexpensive, easily administered assessment tool that can help record qualitative changes in sitting in an objective manner. Objective data are useful to document treatment efficacy over time. Over the past 2 years, the Slump Test has been administered at our clinic to a varied population with respect to age, neuromuscular condition, and functional abilities. At the time of this writing, more than 200 children have had the Slump Test administered as part of their assessment protocol. Most of these children have been between the ages of 3 and 8 years; have cerebral palsy, decreased trunk control, and limb spasticity; and are dependent on a wheelchair or aide for ambulation. In conclusion, the picture representation and objective data obtained from the Slump Test along with a qualitative description of sitting have provided us with a useful means of assessing change over time. | 10.5014/ajot.46.3.271 |
pubmed_72_19925 | Biofilms are three-dimensional structures formed by surface-attached microorganisms and their extracellular products. Biofilms formed by pathogenic microorganisms play an important role in human diseases. Higher resistance to antimicrobial agents and changes in microbial physiology make treating biofilm infections very complex. Atmospheric pressure nonthermal plasmas (NTPs) are a novel and powerful tool for antimicrobial treatment. The microbicidal activity of NTPs has an unspecific character due to the synergetic actions of bioactive components of the plasma torch, including charged particles, reactive species, and UV radiation. This review focuses on specific traits of biofilms, their role in human diseases, and those effects of NTP that are helpful for treating biofilm infections. The authors discuss NTP-based strategies for biofilm control, such as surface modifications to prevent bacterial adhesion, killing bacteria in biofilms, and biofilm destruction with NTPs. The unspecific character of microbicidal activity, proven polymer modification and destruction abilities, low toxicity for human tissues and absence of long-living toxic compounds make NTPs a very promising tool for biofilm prevention and control. | 10.1116/1.4914382 |
pubmed_874_9977 | Hemolytic uremic syndrome (HUS), the most common cause of acute renal failure in childhood, is mainly caused by infection with Shiga toxin (Stx)-producing enterohemorrhagic Escherichia coli (EHEC). Besides its cytotoxic activity, Stx has been shown to interact with the complement system. Complement breakdown products have been found in serum of HUS patients suggesting complement activation and in vitro studies have demonstrated that Stx2 directly activates complement leading to formation of terminal complement complex. Furthermore, Stx2 has been found to bind to factor H (FH) resulting in a reduced cofactor activity on the cell surface. Binding of Stx2 has also been shown for other members of the FH family, namely FH-like protein 1 and FH-related protein 1. Both proteins also compete with FH for Stx binding, so that in the presence of FHR-1 less FH is bound to Stx and therefore more is available for endothelial cell protection. In addition, Stx2 has been demonstrated to downregulate the membrane-bound regulator CD59 on the surface of glomerular endothelial and tubulus epithelial cells on protein and at the mRNA level. In conclusion, Stx modulates complement regulator proteins leading to an impaired control and thus to enhanced complement activation. Its implication in the pathogenesis of EHEC-induced HUS in vivo and whether complement blockage might be a therapeutic option still has to be elucidated. | 10.1055/s-0034-1375295 |
pubmed_501_7709 | A young man with progressive systemic sclerosis (PSS) and pulmonary complaints exhibited enlarging lung cysts on chest x-ray. These rather uncommon findings in PSS result from alveolar dissolution and obstructive emphysema. Diffuse pulmonary fibrosis is basic to this process as well as to the more familiar pulmonary roentgen changes in PSS. | pubmed_501_7709 |
pubmed_158_15498 | An increasingly significant cause of disease in the immunodeficient patient, herpesviruses continue to be a concern in dentistry. Today's dentist must be aware of infections caused by CMV and EBV as well as HSV and VZV. Human herpesviruses 6 and 7 are not yet associated with a particular oral disease, but 80 percent to 90 percent of patients can be expected to shed these viruses in their saliva. Most recently, a new herpesvirus, HHV-8, was postulated associated with Kaposi's sarcoma. An update of information related to the diagnosis, prevention and treatment of herpesvirus infections is presented. | pubmed_158_15498 |
pubmed_674_7427 | There are an increasing number of radiation therapy patients with hip prosthesis. The common method of minimizing treatment planning inaccuracies is to avoid radiation beams to transit through the prosthesis. However, the beams often exit through them, especially when the patient has a double-prosthesis. Modern treatment planning systems employ algorithms with improved dose calculation accuracies but even these algorithms may not predict the dose accurately at high atomic number interfaces. The current study evaluates the dose calculation accuracy of three common dose calculation algorithms employed in two commercial treatment planning systems. A hip prosthesis was molded inside a cylindrical phantom and the dose at several points within the phantom at the interface with prosthesis was measured using thermoluminescent dosimeters. The measured doses were then compared to the predicted ones by the planning systems. The results of the study indicate all three algorithms underestimate the dose at the prosthesis interface, albeit to varying degrees, and for both low- and high-energy x rays. The measured doses are higher than calculated ones by 5-22% for Pinnacle Collapsed Cone Convolution algorithm, 2-23% for Eclipse Acuros XB, and 6-25% for Eclipse Analytical Anisotropic Algorithm. There are generally better agreements for AXB algorithm and the worst results are for the AAA. | 10.1002/acm2.12060 |
pubmed_178_16411 | Mohs surgery, as it has evolved since its inception by Dr. Mohs, is a technique for removal of certain cancers using careful, precise microscopic marginal control. The contemporary technique using fresh tissue is detailed, illustrating advantages that include maximal conservation of normal surrounding tissue and structures, an extremely high cure rate, and a tumor-free defect which can be reconstructed immediately. The indications and applications for Mohs surgery, once limited to large recurrent basal cell carcinomas, have expanded to include several cutaneous and paracutaneous neoplasms. These, with an emphasis on certain basal cell carcinomas, are discussed in detail. With better understanding of the Mohs technique, its indications, applications, and advantages, an interdisciplinary approach to certain cutaneous and paracutaneous neoplasms is proposed. | 10.1002/hed.2890060209 |
pubmed_592_22342 | PURPOSE
To determine the utility of MR imaging in the evaluation of lingual carcinomas.
MATERIAL AND METHODS
Eleven patients with lingual carcinoma were evaluated with MR imaging including dynamic study within one week before surgery. Nine patients underwent preoperative chemotherapy or irradiation, and 2 patients had no preoperative treatment. Delineation of the tumor, the contrast between tumor and surrounding tissue, and extent of the tumor were evaluated in a blinded manner. After glossectomy, MR images were correlated with pathological findings. Statistical analysis was performed on the visual assessment ratings.
RESULTS
Blinded evaluation suggested that dynamic and T2-weighted images (T2WI) were significantly superior to postcontrast T1WI in demonstrating the lesion. There were no significant differences between dynamic MR images and T2WIs. However, histopathological correlation showed that in patients with preoperative treatment, dynamic MR imaging demonstrated more accurately the size and extent of the residual tumor than did T2WI and postcontrast T1WI, which tended to demonstrate an area of signal abnormality that was more extensive than the true size of the residual lesion. In patients without preoperative treatment, dynamic MR imaging, T2WI, and postcontrast T1WI gave an equivalent depiction of the extent of the carcinoma.
CONCLUSION
In patients with no preoperative treatment, dynamic MR imaging does not appear to offer any advantage over T2WI. However, in patients with preoperative treatment, dynamic MR imaging provides a more accurate assessment of the residual tumor than do T2WI and postcontrast T1WI. | 10.1177/02841851960373P257 |
pubmed_751_2059 | We have evaluated the reliability of the transcutaneous (t.c.) method of measurement of arterial PO2 and PCO2 in adult man. In 33 simultaneous measurements of 9 normals and 12 patients with a wide range of hypoxemia, we found: t.c. PCO2 = 3.62 + 1.29 PaCO2 +/- 7.3 (r = 0.96) and t.c. PO2 = 11.14 + 0.86 PaO2 +/- 9.89 (r = 0.92). Recalculating t.c. PCO2 to 37 degrees C we can obtain: t.c. PCO2 = 2.7 + 0.97 X PaCO2, stating that there is no significant difference between t.c. PCO2 and PaCO2. The t.c. apparatus detects 10 and 90% O2 pressure changes with a delay of time of about 15 s and 1 min, respectively; the t.c. method is therefore not suitable for detecting changes in PaO2 caused by sleep apnea of short duration. On the contrary the t.c. method provided a useful monitoring of arterial PO2 and PCO2 changes during the night in chronic obstructive pulmonary disease (COPD) and non-COPD patients. A nocturnal monitoring of t.c. PO2 and PCO2 seems: (a) absolutely necessary in non-COPD hypoxemics, especially if total lung capacity (TLC) and/or residual volume (RV) are significantly reduced; (b) not absolutely necessary in COPD hypoxemics, provided they have an enlarged TLC and/or a very expanded RV; (c) advisable in intermediate situations, e.g., in COPD hypoxemics with an associated restrictive disorder caused by heart failure, congestion of pulmonary bed, parenchymal or rib cage disease, in order to establish the optimal concentration of oxygen for each patient and to avoid severe nocturnal hypoxemia without producing a dangerous rise in PaCO2. | 10.1159/000194804 |
pubmed_791_14137 | The establishment and development of a set of methods of oil accurate recognition in a different environment are of great significance to the effective management of oil spill pollution. In this work, the concentration-emission matrix (CEM) is formed by introducing the concentration dimension. The principal component analysis (PCA) is applied to extract the spectral feature. The classification methods, such as Probabilistic Neural Networks (PNNs) and Genic Algorithm optimization Support Vector Machine (SVM) parameters (GA-SVM), are used for oil identification and the recognition accuracies of the two classification methods are compared. The results show that the GA-SVM combined with PCA has the highest recognition accuracy for different oils. The proposed approach has great potential in rapid and accurate oil source identification. | 10.3390/molecules25215124 |
pubmed_515_18368 | Children commonly report musculoskeletal discomfort related to different activities such as computer use, playing electronic games, watching TV, reading, and performing physical and hand intensive activities. Discomfort can result in disability and is a strong predictor of future discomfort in adulthood. Adult beliefs regarding discomfort can affect the level of disability and are modifiable. Children's beliefs regarding discomfort could potentially be modified to minimise disability related to musculoskeletal disorders. The aim of this study was to describe children's beliefs about why they experience musculoskeletal discomfort, both in general and related to specific activities. Eighty eight school children completed questionnaires on frequency and usual duration of nine activities, whether they had felt discomfort and what they believed was the cause of any discomfort in relation to those activities. The most common activity was TV watching, and most activities were performed for 1 hour or shorter. Bad posture and doing too much of a certain activity were the most common beliefs regarding reasons for discomfort. This study shows that children are developing beliefs that tend to reflect scientific knowledge about risk factors. These beliefs could be incorporated into preventative health interventions. | 10.3233/WOR-2009-0825 |
pubmed_299_17791 | Wound therapy remains a clinical challenge. Incorporation of growth factors (GFs) into heparin-functionalized polymer hydrogel is considered as a promising strategy to improve wound healing efficiency. However, different GFs incorporation into the same heparin-based hydrogels often lead to different wound healing effects, and the underlying GF-induced wound healing mechanisms still remain elusive. Herein, we developed a thermos-sensitive heparin-poloxamer (HP) hydrogel to load and deliver different GFs (aFGF and bFGF) for wound healing in vivo. The resulting GFs-based hydrogels with and without HP hydrogels were systematically evaluated and compared for their wound healing efficiency by extensive in vivo tests, including wound closure rate, granulation formation, re-epithelization, cell proliferation, collagen, and angiogenesis expressions. While all GFs-based dressings with and without HP hydrogels exhibited better wound healing efficacy than controls, both HP-aFGF and HP-bFGF hydrogels demonstrated their superior healing activity to improve wound closure, granulation formation, re-epithelization, and blood vessel density by up-regulation of PCNA proliferation and collagen synthesis, as compared to GF dressings alone. More importantly, HP-aFGF dressings exhibited the higher healing efficacy than HP-bFGF dressings, indicating that different a/bFGF surface properties lead to different binding and release behaviors in HP hydrogels, both of which will affect different wound healing efficiency. On the basis of experimental observations, the working mechanisms of different healing effects of HP-GFs on full skin removal wound were proposed. This work provides different views of the design and development of an effective hydrogel-based delivery system for GFs toward rapid wound healing. | 10.1021/acsami.6b06047 |
pubmed_564_2365 | Vitamin A (retinol) is required for the normal mucociliary differentiation of respiratory epithelium. A depletion of vitamin A promotes squamous cell metaplasia. To understand how vitamin A suppresses squamous cell differentiation, the expression of a squamous cell differentiation marker, the small proline-rich protein gene (spr1), was studied in cultured monkey tracheobronchial epithelial (TBE) cells. The expression of the spr1 gene was inhibited about 40 fold by retinol. The mRNA levels of the spr1 gene started to decline within 6 h of retinol treatment and reached a minimum level after 7 days. The inhibition by retinol was concentration dependent and did not require concurrent protein synthesis. The inhibition of the spr1 mRNA by retinol was not due to a decrease in the transcription rate of its gene but due to a decrease in its stability, as determined by nuclear run-on assays and mRNA half-life measurement, respectively. This result was further supported by a DNA transfection study using a chimeric construct containing the spr1 promoter region and the chloramphenicol acetyltransferase (CAT) reporter gene. The CAT activity in transfected cells was not inhibited by retinol. These results suggest that spr1 gene expression is posttranscriptionally down-regulated by retinol. | 10.1002/jcp.1041570316 |
pubmed_994_14848 | With the emergence of new therapies, established patterns of treating advanced melanoma are changing. The aim of this study was to understand how advanced melanoma is treated in clinical practice in Europe following the introduction of ipilimumab and vemurafenib. An online survey was conducted between August and November 2012 with 150 oncologists and dermatologists, from France, Germany, Italy, Spain and the U.K.; respondents reported treating the majority of patients with one or two lines of therapy. For BRAF mutant melanoma, the most frequently used first-line treatments were vemurafenib and dacarbazine. For BRAF wild-type melanoma, the most frequently used first-line treatment was dacarbazine. There was no single preferred agent for the second-line treatment of BRAF mutant or BRAF wild-type disease. Most sequencing from first- to second-line was from conventional dacarbazine to newer agents such as ipilimumab and vemurafenib. The treatment of advanced melanoma is rapidly evolving due to the introduction of new agents. This study presents an early insight into access to the new agents, ipilimumab and vemurafenib, and clinical practice in several European countries. | 10.1111/ecc.12326 |
pubmed_167_24498 | Epithelial tissues are composed of layers of tightly connected cells shaped into complex three-dimensional (3D) structures such as cysts, tubules, or invaginations. These complex 3D structures are important for organ-specific functions and often create biochemical gradients that guide cell positioning and compartmentalization within the organ. One of the main functions of epithelia is to act as physical barriers that protect the underlying tissues from external insults. In vitro, epithelial barriers are usually mimicked by oversimplified models based on cell lines grown as monolayers on flat surfaces. While useful to answer certain questions, these models cannot fully capture the in vivo organ physiology and often yield poor predictions. In order to progress further in basic and translational research, disease modeling, drug discovery, and regenerative medicine, it is essential to advance the development of new in vitro predictive models of epithelial tissues that are capable of representing the in vivo-like structures and organ functionality more accurately. Here, we review current strategies for obtaining biomimetic systems in the form of advanced in vitro models that allow for more reliable and safer preclinical tests. The current state of the art and potential applications of self-organized cell-based systems, organ-on-a-chip devices that incorporate sensors and monitoring capabilities, as well as microfabrication techniques including bioprinting and photolithography, are discussed. These techniques could be combined to help provide highly predictive drug tests for patient-specific conditions in the near future. | 10.3389/fbioe.2018.00197 |
pubmed_707_9486 | Amenamevir has been approved for the treatment of herpes zoster (HZ); however, its therapeutic efficacy against central nervous system (CNS) infection may be insufficient due to its low spinal fluid permeability. We herein report a case of aseptic meningitis in a 91-year-old Japanese man treated with amenamevir for HZ in the trigeminal nerve region. Several cases of CNS infection have been reported in patients receiving amenamevir treatment for HZ. Patients with CNS complications often have skin rashes near the trigeminal region. Thus, we should be alert for signs of CNS infection when administering amenamevir to patients with such rashes. | 10.2169/internalmedicine.8581-21 |
pubmed_475_6593 | An imaging method using spectral analysis combined with advanced linear unmixing was used to allow histolocalization of natural autofluorescent compounds such as hydroxycinnamic acid (chlorogenic acid) and xanthone (mangiferin) in living cells and tissues (mature coffee leaves). The tested method included three complementary steps: 1/ visualization of natural autofluorescence and spectrum acquisition with a multiphoton microscope; 2/ identification of some compounds using previous information on the chemical composition of the tissue, obtained from litterature; and 3/ localization of candidate compounds by spectral imaging. The second part of the study consisted of describing the histochemical structure of leaves during their development. This revealed very fast histochemical differentiation of leaves during the first week after their emergence. Lastly, young leaves of Coffea pseudozanguebariae (PSE), C. eugenioides (EUG), C. arabica (ARA) and C. canephora (CAN) were compared. This confirmed the presence of xanthone in PSE and EUG, but especially its precise tissue localization. This also highlighted the paternal CAN origin of the leaf structure in the allotetraploid species ARA. The limits and advantages of the method without staining are discussed relative to classical epifluorescence microscopy under UV light. This non-invasive optical technique does not require pretreatment and is an effective experimental tool to differentiate multiple naturally-occuring fluorochores in living tissues. | 10.3389/fpls.2014.00039 |
pubmed_22_23443 | Excessive tooth structure loss is a common iatrogenic error encountered during endodontic practice. Conservative treatment planning is essential to maintain the structural integrity in such teeth. This case report elucidates a novel approach in sculpting Biodentine as a dentin substitute followed by internal bleaching and restoration with fiber-reinforced composite. | 10.4103/JCD.JCD_311_16 |
pubmed_675_25052 | Human zygotes are difficult to obtain for research because of limited resources and ethical debates. Corrected human tripronuclear (ch3PN) zygotes obtained by removal of the extra pronucleus from abnormally fertilized tripronuclear (3PN) zygotes are considered an alternative resource for basic scientific research. In the present study, eight-cell and blastocyst formation efficiency were significantly lower in both 3PN and ch3PN embryos than in normal fertilized (2PN) embryos, while histone H3 lysine 9 trimethylation (H3K9me3) levels were much higher. It was speculated that the aberrant H3K9me3 level detected in ch3PN embryos may be related to low developmental competence. Microinjection of 1000 ng/µl lysine-specific demethylase 4A (KDM4A) mRNA effectively reduced the H3K9me3 level and significantly increased the developmental competence of ch3PN embryos. The quality of ch3PN zygotes improved as the grading criteria, cell number and pluripotent expression significantly increased in response to KDM4A mRNA injection. Developmental genes related to zygotic genome activation (ZGA) were also upregulated. These results indicate that KDM4A activates the transcription of the ZGA program by enhancing the expression of related genes, promoting epigenetic modifications and regulating the developmental potential of ch3PN embryos. The present study will facilitate future studies of ch3PN embryos and could provide additional options for infertile couples. | 10.1093/molehr/gaab012 |
pubmed_372_21493 | BACKGROUND
Vivax malaria is a neglected disease. There is an irrefutable need for better treatments with higher acceptability and efficacy. The treatment efficacy is influenced by many factors, including bioavailability. Hence, a straightforward strategy to improve vivax malaria treatment efficacy is the deployment of good quality formulations of primaquine and chloroquine. As these treatments were developed more than 70 years ago, many of the available data on blood levels of both drugs are based on obsolete analytical methodologies or pharmaceutical formulations, which are not available anymore. Herein, the results of three bioequivalence studies are presented, providing individual pharmacokinetic data on chloroquine and primaquine of more than a hundred healthy volunteers and using up-to-date analytical methods.
METHODS
Three trials were designed as a single centre, randomized, single dose, open label, fasting, crossover bioequivalence studies comparing a new coated chloroquine tablet to the uncoated tablet, and 5 and 15 mg primaquine formulations to either an international reference product or the currently distributed tablets. Plasma concentrations of chloroquine and primaquine were measured using a validated HPLC-MS/MS method in accordance with current international regulatory requirements for bio-analytical methods.
RESULTS
In total, a hundred eleven healthy volunteers of both genders were included in the three studies (n = 32; 30 and 56 respectively). No serious adverse events occurred. Drugs levels were measured in 5,520 blood samples. The estimated ratio of the geometric means of Cmax, AUC0-t and AUC0-inf of test and reference drugs and their 90% CI for chloroquine 150 mg, primaquine 15 mg and primaquine 5 mg were: 95.33% (89.18; 101.90), 86. 85% (82.61; 91.31), and 84.45% (76.95; 92.67); 93.28% (81.76; 106.41), 94.52% (86.13; 103.73) and 93.93% (85.83; 102.79); 97.44% (90.60; 104.78), 93.70% (87.04; 100.87) and 91.36% (85.27; 97.89), respectively. As Cmax and AUC0-t 90% CI were within the acceptance interval of 80-125% in all cases, the formulations tested were bioequivalent.
CONCLUSIONS
In conclusion, the three studies provided detailed chloroquine and primaquine pharmacokinetic data in accordance with current regulatory standards. Together with other open data initiatives, this individual data may increase the accuracy of pharmacokinetic models guiding best dose, new combinations, regimens and formulations to optimize the current chloroquine and primaquine treatments for vivax malaria. The data presented here may support the deployment of high-quality drugs and evidence-based public health policies. | 10.1186/s12936-021-04035-z |
pubmed_236_21966 | Using the hydrogen gas clearance method, a plate-type probe was attached to the surface of the cuff of an endotracheal tube in order to measure the ischemic changes in the tracheal mucosa produced by peritracheal lymph node dissection. In eight human subjects with intrathoracic esophageal carcinoma, the tracheal mucosal blood flow was 40.1 ml/100 g per minute after they had undergone a right thoracotomy and then decreased to 13.0 ml/100 g per minute after they had further received an extended radical operation preserving the right bronchial artery. No tracheal ulcers were seen. The same ischemic changes in the tracheal mucosa were also measured in dogs. The right bronchial artery contributes about one-third of the total blood flow to the trachea and this was thus calculated to be about 10-14 ml/100 g per minute. | 10.1007/BF01833720 |
pubmed_957_19665 | Lack of basic knowledge about the external and internal anatomies of the root canal system and common variations in teeth may lead to various procedural errors or treatment failure. In this study, the root canal configurations of mandibular incisors and the symmetry of the contralateral incisors of Saudi Arabian subpopulations were analyzed and determined using cone beam computed tomography (CBCT). A retrospective evaluation of 700 patients was conducted, and 1260 fully developed permanent mandibular central incisors were assessed. The number of root canals was determined, and the internal root canal anatomies were categorized based on Ahmed et al.'s criteria. The CBCT images were independently evaluated by 2 trained dentists and an endodontist. The data were assessed using the chi-square and one-way analysis of variance tests. All the mandibular central incisors included in the study were single-rooted. According to Ahmed et al's classification system, the most common classification (82.6%) was 1ManA1 (Vertucci type I), followed by 1ManA1-2-1 (Vertucci type III; 13%). Second canals were more frequently recorded in the male participants than in the female participants. The root canal configuration between contralateral incisors was largely symmetrical. Most of the mandibular incisors in the examined Saudi Arabian population had a single canal. Nevertheless, a substantial number of patients had a complex root morphology. Hence, CBCT can be utilized as a potential supplementary tool during root canal treatment. | 10.1097/MD.0000000000030751 |
pubmed_987_3144 | Case summary
A 10-year-old male neutered domestic shorthair cat from Quilmes (Province of Buenos Aires, Argentina) presented at the Infectious Diseases and Parasitology Unit with a hyperpigmented nodule of 5 cm diameter on the nasal plane with a small ulceration of more than 1 year's evolution. A scaly and hyperpigmented alopecic lesion of 3 cm in diameter was found on the lower edge of the tail. The patient was under immunosuppressive therapy with corticosteroids for lymphoplasmacytic duodenitis. Samples of the lesion present on the nasal plane were taken under a surgical procedure. In the wet mount preparations, pigmented irregular hyphae were observed. They developed dark colonies when cultured on Sabouraud medium. On micromorphology, structures compatible with Phialophora species were identified. PCR and sequencing of ITS (ITS1-5.8S-ITS2) confirmed Phialophora americana as the etiologic agent. A therapeutic scheme that included a combination of itraconazole oral solution (1.5 mg/kg PO q12h) with terbinafine (30 mg/kg PO q24h) was indicated for a period of 10 months. The patient died of complications resulting from its underlying disease.
Relevance and novel information
As far as the authors are aware, this is the first study to report P americana as an etiologic agent of phaeohyphomycosis in cats. In this case study, the species was identified using molecular tests. | 10.1177/20551169221077611 |
pubmed_597_16795 | BACKGROUND
Resection of a retrocaval paraganglioma is technically challenging due to limited tumor accessibility and proximity to the vena cava.
CASE PRESENTATION
A large, malignant paraganglioma was found behind the retrohepatic segment of the inferior vena cava of a 60-year-old male. During resection of this rare paraganglioma, the left lateral lobe of the liver, a portion of the caudate lobe of the liver, and the gallbladder were also removed. Unfortunately, the patient died six months after surgery due to hepatic metastasis.
CONCLUSION
This case demonstrates that a partial hepatectomy may be necessary to improve tumor accessibility during resection of a retrocaval paraganglioma, particularly if the tumor is proximal to the vena cava. Furthermore, palliative treatments may help prevent tumor recurrence and metastasis of malignant paragangliomas. | 10.1186/1471-2482-13-49 |
pubmed_912_21409 | Positive effects of yeast concentrate on immunity and performance of weaned piglets have been reported. However, the effects on innate immunity were not examined. Natural antibodies (NAb) are part of innate immunity and have been related to health and survival in fish, poultry, rodents, and man. Yeast cell walls may also affect innate immunity of weaned piglets. We studied the effect of Nuklospray ProHealth containing a spray dried blend of dairy-based feed ingredients, vegetable fats, and processed yeast cell walls as protein source on NAb levels and performance of weaned piglets. A total of 120 piglets weaned at 28 d of age were assigned 2 treatments comprising a control diet and an experimental diet with the test product. Piglets were housed in groups of 6 during the first 4 weeks after weaning. Blood samples of 20 healthy nonmedicated piglets per treatment were taken at days 0, 14, and 28 after weaning and analyzed for NAb levels binding keyhole limpet hemocyanin by an indirect ELISA procedure. Performance parameters also were determined. Overall, the experimental diet tended to improve feed intake (574 vs. 522 g/d; P < 0.1), ADG (449 vs. 412 g/d; P < 0.1), and final BW (21.4 vs. 20.3 kg; P = 0.08) compared to the control diet. No differences were found in feed conversion ratio or fecal score. At day 0, no differences in NAb levels were found, but on day 14 after weaning, NAb levels of piglets fed the experimental diet were significantly higher than of piglets fed the control diet (2.05 vs. 1.70; P < 0.05). On day 28 after weaning no differences were found. These results indicate that day 14 postweaning levels of NAb as a parameter of innate immunity were improved and indicate a tendency for improvement of postweaning performance of piglets fed diets supplemented with Nuklospray ProHealth. | 10.2527/jas.51742 |
pubmed_154_20743 | Molecular data permit to construct phylogenetic trees independently of morphological characters. It allows to consider their evolution without the frames of a priori hypothesis of regularities of morphological evolution and independently of palaeontological data. Cladistic analysis of elements of secondary structure of varible areas V7 and V2 in 18S rRNA with different Protozoa as "external" groups shows that Bilateria + Cnidaria are monophyletic, Ctenophora and Porifera are early derivatives of Metazoa, Trichoplax (Placozoa) is a form related to Cnidaria, while Rhombozoa, Orthonectida and Myxozoa were branched within Bilateria. Morphological reduction with losses of any organs and tissues took place many times in early evolution of Metazoa and Bilateria not only in parasitic species. It occurred both at early and late stages of embryonic development and differentiation. Two alternative scenario of morphological degeneration in Trichoplax and the way of their testing are suggested. The similarity of Ctenophora and Calcarea is discussed. Meridional or oblique position of the third cleavage furrow of ovule can be considered as an evidence of their origin from common ancestor. | pubmed_154_20743 |
pubmed_962_14261 | The aim of this study was to develop an automated sampling method to measure lovastatin in a conscious and freely moving rat. The blood samples were collected by means of the automated blood sampling system DR-II and the faecal samples were collected using a metabolic cage. The concentration of lovastatin was determined by a reversed-phase liquid chromatographic system with a UV absorbance detector. The mobile phase contained acetonitrile and 10 mm NaH2PO4 in the proportions 60:40 (v/v) with a flow-rate of 1 mL/min. The calibration curve was linear in concentration ranges of 0.05-100 and 0.1-100 microg/mL for lovastatin in blood and faecal samples, respectively. Following pharmacokinetic analysis, we identified that the maximum plasma concentration was around 1.18 +/- 0.08 microg/mL at concentration peak time 120 min and almost 78% of loading dose was accumulated in the faeces within 48 h after lovastatin administration (500 mg/kg, p.o.). | 10.1002/bmc.618 |
pubmed_344_11487 | There is currently much interest in assisted reproduction techniques in the horse, however, many aspects of oocyte maturation, fertilization, and embryo development in the horse differ from those in other species. Because of the close attachment of the equine oocyte to the follicle wall, scraping of the follicle is the most effective method for oocyte recovery. A notable feature of equine oocytes is that those with expanded cumuli (Ex oocytes), which originate from atretic follicles, have higher meiotic competence (ability to mature to metaphase II in vitro) than do oocytes with compact cumuli (Cp oocytes). Cp oocytes originate in viable follicles but are largely juvenile. Recovery and culture of equine oocytes immediately after slaughter yields a higher maturation rate than that obtained from oocytes after ovary storage; this is related to damage to chromatin in Cp oocytes during storage. In contrast, developmental competence (rate of blastocyst development in vitro) is higher in oocytes recovered from the ovary after a delay. The optimum duration of maturation varies based on cumulus morphology and time of recovery from the ovary, but there is no difference in developmental competence between Ex and Cp oocytes. Because standard in vitro fertilization is not repeatable in the horse, oocyte transfer (surgical transfer of oocytes to the oviducts of inseminated mares) has been developed to allow fertilization of isolated oocytes. Fertilization in vitro may be achieved using intracytoplasmic sperm injection; culture of injected oocytes in a medium with high glucose can yield over 30% blastocyst development. | 10.1002/mrd.21186 |
pubmed_336_472 | AIMS
Genetic predisposition for cardiovascular disease (CVD) is likely to be modified by environmental exposures. We tested if the associated risk of CVD and CVD-mortality by the single nucleotide polymorphism rs4977574 on chromosome 9p21 is modified by life-style factors.
METHODS AND RESULTS
A total of 24,944 middle-aged subjects (62% females) from the population-based Malmö-Diet-and-Cancer-Cohort were genotyped. Smoking, education and physical activity-levels were recorded. Subjects were followed for 15 years for incidence of coronary artery disease (CAD; N = 2309), ischemic stroke (N = 1253) and CVD-mortality (N = 1156). Multiplicative interactions between rs4977574 and life-style factors on endpoints were tested in Cox-regression-models. We observed an interaction between rs4977574 and smoking on incident CAD (P = 0.035) and CVD-mortality (P = 0.012). The hazard ratios (HR) per risk allele of rs4977574 were highest in never smokers (N = 9642) for CAD (HR = 1.26; 95% CI 1.13-1.40; P<0.001) and for CVD-mortality (HR = 1.40; 95% CI 1.20-1.63; P<0.001), whereas the risk increase by rs4977574 was attenuated in current smokers (N = 7000) for both CAD (HR = 1.05; 95%CI 0.95-1.16; P = 0.326) and CVD-mortality (HR = 1.08; 95%CI 0.94-1.23; P = 0.270). A meta-analysis supported the finding that the associated increased risk of CAD by the risk-allele was attenuated in smokers. Neither education nor physical activity-levels modified the associated risk of CAD, ischemic stroke and CVD mortality conferred by rs4977574.
CONCLUSION
Smoking may modify the associated risk of CAD and CVD-mortality conferred by genetic variation on chromosome 9p21. Whether the observed attenuation of the genetic risk reflects a pathophysiological mechanism or is a result of smoking being such a strong risk-factor that it may eliminate the associated genetic effect, requires further investigation. | 10.1371/journal.pone.0085893 |
pubmed_960_5479 | Lithium is the standard first line of treatment for bipolar disorder. Because of its potential toxicity, levels of the drug have to be constantly monitored. To this end, an accurate and rapid assay is thus required. Moreover, lithium measurement allows differential diagnosis in patients with hallucinations, dementia and amnesia. The lithium concentration in blood is usually evaluated by flame photometry, atomic absorption spectroscopy or ion selective electrode. The aim of this study was to evaluate the analytical performance of a new colorimetric assay for lithium. Within-day precision of a pool with a target value of 1.25 mmol/l was 2.18% (CV) and day-to-day precision was assessed using serum aliquots containing two concentrations of lithium, and CVs were 5.47 and 1.6% at 0.6 and 1.15 mmol/l, respectively. The lower detection limit (LLD) was <0.08 mmol/l. The assay seemed to be linear up to 5 mmol/l. Results of a comparison method using Deming regression were: y=1.161x-0.0075 (r=0.9879) for regression with the Flame Photometer and y=0.9729 x+0.0133 (r=0.9787) for regression with atomic absorption spectroscopy. Moreover, in this study we did not find any interference with drugs or other analytes tested. In conclusion, this assay may be a method of choice for measuring lithium blood concentrations, especially in emergency situations. | 10.1515/CCLM.2004.214 |
pubmed_965_22700 | Prophenoloxidase (proPO) is a melanin-synthesising enzyme that plays important roles in immune responses by crustaceans. Previously, we cloned and characterized proPO-I from white shrimp, Litopenaeus vannamei. In the present study, a novel prophenoloxidase-II (proPO-II) cDNA was also cloned from haemocytes of L. vannamei using oligonucleotide primers and reverse-transcriptase polymerase chain reaction (RT-PCR). Both 3'- and 5'-regions were isolated by the rapid amplification of complementary (c)DNA end (RACE) method. The 2504-bp cDNA contained an open reading frame (ORF) of 2073 bp, an 84-bp 5'-untranslated region, and a 347-bp 3'-untranslated region containing the poly A tail. The molecular mass of the deduced amino acid sequence (691 amino acids) was 78.8 kDa with an estimated pI of 6.07. It contains two putative tyrosinase copper-binding motifs and a conserved C-terminal region common to all known proPOs. Comparisons of the amino acid sequences showed that white shrimp proPO-II is more closely related to the proPO of other penaeids than to that of crayfish, lobsters, crab, or a freshwater prawn, and is the ancestor type of known penaeid proPOs. proPO-I and proPO-II messenger (m)RNAs of shrimp were located on different loci, and were constitutively expressed mainly in haemocytes. The transcriptional regulation of these two proPOs in shrimp at different molt stages, those administered dietary sodium alginate, and those challenged with Vibrio alginolyticus were surveyed. The results showed that the proPOs may be directly involved in the acute-phase immune defence, and proPO-II may contribute earlier to immune defence in shrimp injected with V. alginolyticus, and it may be regulated by ecdysone. However, a similar effect was found by stimulating proPO-I and proPO-II mRNA expression in shrimp fed a sodium alginate-containing diet. Results of this study provide a basis for developing a comprehensive understanding of expression/function relationships of individual proPOs in shrimp. | 10.1016/j.fsi.2008.10.003 |
pubmed_732_10074 | Trifluoromethylated ketones are useful building blocks for organic compounds with a trifluoromethyl group. A new and facile synthesis of ketones with a trifluoromethyl substituent in the α-position proceeds through a one-pot photoredox-catalyzed trifluoromethylation-oxidation sequence of aromatic alkenes. Dimethyl sulfoxide (DMSO) serves as a key and mild oxidant under these photocatalytic conditions. Furthermore, an iridium photocatalyst, fac[Ir(ppy)3 ] (ppy=2-phenylpyridine), turned out to be crucial for the present photoredox process. | 10.1002/anie.201403590 |
pubmed_962_14439 | In psychiatry, individual-based registries have provided key information on risks and benefits associated with the use of psychotropic drugs but they have rarely been employed for monitoring and evaluating the everyday prescribing of psychopharmacological treatments. This article describes the cultural background that gave impetus to the idea of registering all prescriptions of psychotropic drugs dispensed by physicians working in the South Verona community mental health service, and presents the methodology employed to develop such a registry in a community psychiatric service where a psychiatric case register (PCR) has been operating since 1978. We developed a registry including every patient receiving psychotropic medications in ordinary practice. This registry is linked to the PCR in order to obtain data on social and demographic characteristics, clinical symptoms, diagnosis, use of services, and outcomes. No exclusion criteria are allowed--anyone receiving treatment is automatically included. This system, which can link drug and service-use data with hard outcome indicators, can generate information on the proportion of subjects discontinuing treatment, switching medication because of side-effects, recovery or inefficacy, as well as on the proportion of subjects failing to return to the physician, and the proportion of patients who improve. The innovative aspect of this approach is that this registry is developed, organized and used by physicians interested in monitoring their clinical practice and in providing patients, relatives and the public with accurate information on drug use in their specific context of care. | 10.1002/mpr.1 |
pubmed_456_15689 | BACKGROUND
Visceral hypersensitivity is considered to play a vital role in the pathogenesis of irritable bowel syndrome (IBS). Neurotrophins have drawn much attention in IBS recently. Brain-derived neurotrophic factor (BDNF) was found to mediate visceral hypersensitivity via facilitating sensory nerve growth in pre-clinical studies. We hypothesized that BDNF might play a role in the pathogenesis of diarrhea-predominant IBS (IBS-D).
AIM
To investigate BDNF levels in IBS-D patients and its role in IBS-D pathophysiology.
METHODS
Thirty-one IBS-D patients meeting the Rome IV diagnostic criteria and 20 age- and sex-matched healthy controls were recruited. Clinical and psychological assessments were first conducted using standardized questionnaires. Visceral sensitivity to rectal distension was tested using a high-resolution manometry system. Colonoscopic examination was performed and four mucosal pinch biopsies were taken from the rectosigmoid junction. Mucosal BDNF expression and nerve fiber density were analyzed using immunohistochemistry. Mucosal BDNF mRNA levels were quantified by quantitative real-time polymerase chain reaction. Correlations between these parameters were examined.
RESULTS
The patients had a higher anxiety score [median (interquartile range), 6.0 (2.0-10.0) vs 3.0 (1.0-4.0), P = 0.003] and visceral sensitivity index score [54.0 (44.0-61.0) vs 21.0 (17.3-30.0), P < 0.001] than controls. The defecating sensation threshold [60.0 (44.0-80.0) vs 80.0 (61.0-100.0), P = 0.009], maximum tolerable threshold [103.0 (90.0-128.0) vs 182.0 (142.5-209.3), P < 0.001] and rectoanal inhibitory reflex threshold [30.0 (20.0-30.0) vs 30.0 (30.0-47.5), P = 0.032] were significantly lower in IBS-D patients. Intestinal mucosal BDNF protein [3.46E-2 (3.06E-2-4.44E-2) vs 3.07E-2 (2.91E-2-3.48E-2), P = 0.031] and mRNA [1.57 (1.31-2.61) vs 1.09 (0.74-1.42), P = 0.001] expression and nerve fiber density [4.12E-2 (3.07E-2-7.46E-2) vs 1.98E-2 (1.21E-2-4.25E-2), P = 0.002] were significantly elevated in the patients. Increased BDNF expression was positively correlated with abdominal pain and disease severity and negatively correlated with visceral sensitivity parameters.
CONCLUSION
Elevated mucosal BDNF may participate in the pathogenesis of IBS-D via facilitating mucosal nerve growth and increasing visceral sensitivity. | 10.3748/wjg.v25.i2.269 |
pubmed_792_8811 | We have identified Tim9, a new component of the TIM22.54 import machinery, which mediates transport of proteins into the inner membrane of mitochondria. Tim9, an essential protein of Saccharomyces cerevisiae, shares sequence similarity with Tim10 and Tim12. Tim9 is located in the mitochondrial intermembrane space and is organized into two distinct hetero-oligomeric assemblies with Tim10 and Tim12. One complex contains Tim9 and Tim10. The other complex contains Tim9, Tim10 and Tim12 and is tightly associated with Tim22 in the inner membrane. The TIM9.10 complex is more abundant than the TIM9.10.12 complex and mediates partial translocation of mitochondrial carriers proteins across the outer membrane. The TIM9.10.12 complex assists further translocation into the inner membrane in association with TIM22.54. | 10.1093/emboj/18.2.313 |
pubmed_327_12777 | The primary structure of frog neurotensin (fNT) has recently been determined and it has been shown that fNT is a potent stimulator of alpha-MSH secretion by frog pituitary melanotropes. In the present study, we have investigated the effects of fNT on the electrical activity of cultured frog melanotropes by using the patch-clamp technique and we have determined the pharmacological profile of the receptors mediating the effect of fNT. In the cell-attached configuration, fNT (10(-7) M) provoked an increase in the action current discharge followed by an arrest of spike firing. In the gramicidin-perforated patch configuration, fNT (10(-7) M) induced a depolarization accompanied by an increase in action potential frequency and a decrease in membrane resistance. Administration of graded concentrations (10(-10) to 10(-6) M) of fNT or the C-terminal hexapeptide NT(8-13) caused a dose-dependent increase in the frequency of action potentials with EC(50) of 2 x 10(-8) and 5 x 10(-9) M, respectively. The stimulatory effect of fNT was mimicked by various pseudopeptide analogs, with the following order of potency: Boc-[Trp(11)]NT(8-13) > Boc-[D-Trp(11)]NT(8-13) > Boc-[Lys(8,9), Nal(11)]NT(8-13) > Boc-[Psi11,12]NT(8-13). In contrast, the cyclic pseudopeptide analogs of NT(8-13), Lys-Lys-Pro-D-Trp-Ile-Leu and Lys-Lys-Pro-D-Trp-Glu-Leu-OH, did not affect the electrical activity. The NTS1 receptor antagonist and nts2 receptor agonist SR 48692 (10(-5) M) stimulated the spike discharge but did not block the response to fNT. In contrast, SR 142948A (10(-5) M), another NTS1 receptor antagonist and nts2 receptor agonist, inhibited the excitatory effect of fNT. The specific nts2 receptor ligand levocabastine (10(-6) M) had no effect on the basal electrical activity and the response of melanotropes to fNT. In cells which were dialyzed with guanosine-5'-O-(3-thiotriphosphate) (10(-4) M), fNT caused an irreversible stimulation of the action potential discharge. Conversely, dialysis of melanotropes with guanosine-5'-O-(2-thiodiphosphate) (10(-4) M) completely blocked the effect of fNT. Pretreatment of cells with cholera toxin (1 microg/ml) or pertussis toxin (0.2 microg/ml) did not affect the electrical response to fNT. Intracellular application of the G(o/i/s) protein antagonist GPAnt-1 (3 x 10(-5) M) had no effect on the fNT-evoked stimulation. In contrast, dialysis of melanotropes with the G(q/11) protein antagonist GPAnt-2A (3 x 10(-5) M) abrogated the response to fNT. The present data demonstrate that fNT is a potent stimulator of the electrical activity of frog pituitary melanotropes. These results also reveal that the electrophysiological response evoked by fNT can be accounted for by activation of a G(q/11)-protein-coupled receptor subtype whose pharmacological profile shares similarities with those of mammalian NTS1 and nts2 receptors. | 10.1159/000054607 |
pubmed_897_3808 | We reported on 16 new Brazilian patients and review findings in 12 previously reported cases (25 apparently unrelated Brazilian families) from Hospital of Rehabilitation of Craniofacial Anomalies, presenting with Richieri-Costa-Pereira syndrome. All patients display a unique pattern of anomalies consisting of microstomia, micrognathia, abnormal fusion of mandible, cleft palate/Robin sequence, absence of central lower incisors, minor ears anomalies, hypoplastic first ray, abnormal tibiae, hypoplastic halluces, and clubfeet. Learning disability was also a common finding. The sex-ratio showed deviation toward to female (1.8F:1M). Recurrence in sibs was observed in nine instances and consanguinity in 11, supporting the hypothesis of autosomal recessive inheritance. Nineteen of the 25 families lived in São Paulo State, seven of them (10 affected individuals) from an isolated region named "Vale do Ribeira." The geographic barrier of this region associated with the high incidence of the consanguineous matting suggested that this condition is caused by a rare mutation with a founder effect. With the exception of one patient in France, all known cases are of Brazilian origin. The causative gene of this rare syndrome remains unknown. | 10.1002/ajmg.a.33806 |
pubmed_134_12207 | BACKGROUND
In yeast, birds and mammals, the SAPK-interacting protein 1 (Sin1) gene product has been implicated as a component of the stress-activated protein kinase (SAPK) signal transduction pathway. Recently, Sin1 has also been shown to interact with the carboxyl terminal end of the cytoplasmic domain of the ovine type I interferon receptor subunit 2 (IFNAR2). However, the function of Sin1 remains unknown. Since SAPK pathways are ancient and the IFN system is confined to vertebrates, the organization of the Sin1 gene and the sequences of the Sin1 protein have been compared across a wide taxonomic range of species.
RESULTS
Sin1 is represented, apparently as a single gene, in all metazoan species and fungi but is not detectable in protozoa, prokaryotes, or plants. Sin1 is highly conserved in vertebrates (79-99% identity at amino acid level), which possess an interferon system, suggesting that it has been subjected to powerful evolutionary constraint that has limited its diversification.Sin1 possesses at least two unique sequences in its IFNAR2-interacting region that are not represented in insects and other invertebrates. Sequence alignment between vertebrates and insects revealed five Sin1 strongly conserved domains (SCDs I-V), but an analysis of any of these domains failed to identify known functional protein motifs. SCD III, which is approximately 129 amino acids in length, is particularly highly conserved and is present in all the species examined, suggesting a conserved function from fungi to mammals. The coding region of the vertebrate Sin1 gene encompasses 11 exon and 10 introns, while in C. elegans the gene consists of 10 exons and 9 introns organized distinctly from those of vertebrates. In yeast and insects, Sin1 is intronless.
CONCLUSIONS
The study reveals the phylogeny of a little studied gene which has recently been implicated in two important signal transduction pathways, one ancient (stress response), one relatively new (interferon signaling). | 10.1186/1471-2148-5-13 |
pubmed_617_2382 | BACKGROUND
Patients treated with postoperative radiotherapy for endometrial and cervical carcinomas from 1981 to 2000 were retrospectively analysed in order to assess the rate of late small bowel toxicity.
PATIENTS AND METHODS
Eight hundred and six patients had received pelvic irradiation, with total doses of 40-55 Gy. The mean age was 57 years. Three hundred and eighteen patients had been treated for cervical and 488 for endometrial cancer; 46 had diabetes and 22 vascular diseases; 141 had a history of smoking and 367 were previously submitted to surgery for benign diseases. A CT treatment plan had been applied in 285 patients; 256 had been treated by arc moving therapy, 232 with 2 opposed beams (AP-PA) and 318 with 3 or 4 coplanar beams. Three hundred and forty-six were treated with X photons of 10 MV or more, 202 with 4-5 MV and 258 with cobalt gamma rays. Personalized blocks had been used in 389. Thirty-four women had received chemotherapy. Five hundred and eighty-four had been treated with dose fractions of 180 cGy or more and 56 had received a boost with brachytherapy or external beams. Eighty-one had needed treatment discontinuation due to acute small bowel toxicity.
RESULTS
The median follow-up was 70 months. Thirty five patients had bowel obstructions, after a median time of 31 months. The 5- and 10-year toxicity rates were 4 and 7%. Uni- and multivariate comparisons identified age, acute toxicity and dose fraction as predictors for complications.
CONCLUSION
Postoperative pelvic irradiation with standard techniques for gynaecological carcinomas results in tolerable rates of clinically significant late bowel damage, while older patients suffering from significant acute toxicity seem to be at higher risk. | pubmed_617_2382 |
pubmed_968_11916 | Vascular calcification (VC) in macrovascular and peripheral blood vessels is one of the main factors leading to diabetes mellitus (DM) and death. Apart from the induction of vascular calcification, advanced glycation end products (AGEs) have also been reported to modulate autophagy and apoptosis in DM. Autophagy plays a role in maintaining the stabilization of the external and internal microenvironment. This process is vital for regulating arteriosclerosis. However, the internal mechanisms of this pathogenic process are still unclear. Besides, the relationship among autophagy, apoptosis, and calcification in HASMCs upon AGEs exposure has not been reported in detail. In this study, we established a calcification model of SMC through the intervention of AGEs. It was found that the calcification was upregulated in AGEs treated HASMCs when autophagy and apoptosis were activated. In the country, AGEs-activated calcification and apoptosis were suppressed in Atg7 knockout cells or pretreated with wortmannin (WM), an autophagy inhibitor. These results provide new insights to conduct further investigations on the potential clinical applications for autophagy inhibitors in the treatment of diabetes-related vascular calcification. | 10.3389/fphar.2021.692431 |
pubmed_574_2679 | The development of a malignant tumor generally entails a series of events that damage the genome of a somatic cell and result in the malignant phenotype. These events chronicle the malignant progression of a tumor; a dynamic process in which more aggressive and growth-deregulated cell populations are constantly evolving. Gliomas, the most common primary tumors of brain, are known to become increasingly malignant with time. Within recent years, several details of the molecular genetic events associated in their progression have been determined. The earliest events of glioma progression include loss of genetic information from the long arms of chromosomes 13 or 22, or the short arm of chromosome 17 for which targeting of the TP53 (p53) gene has been indicated. Loss of a single complement of type I interferon (IFN) genes from 9p and loss of genetic information from 19q are seen in the tumors of intermediate malignancy grade. Events associated with the most malignant of glial tumors include loss of the second, type I IFN gene complement, loss of genetic information from chromosome 10, and gene amplification (most commonly the epidermal growth factor receptor, in 40% of cases). These findings have helped elucidate the events associated with glial tumorigenesis, and through the identification of specific genes, have provided a starting point for investigating the molecular biology of central nervous system neoplasia. | 10.1096/fasebj.7.10.8344489 |
pubmed_301_6669 | The poly(A)-limiting element (PLE) restricts the length of the poly(A) tail to <20 nt when present in the terminal exon of a pre-mRNA. We previously identified a 65 kDa protein that could be cross-linked to a functional PLE, but not to an inactive mutant element. This binding was competed by poly(U) and poly(C), but not poly(A) or poly(G). Selectivity for the pyrimidine-rich portion of the PLE was demonstrated by RNase footprinting of the binding activity in total nuclear extract. A 65 kDa protein that selectively cross-linked to the functional PLE was purified by conventional chromatography and identified as the large subunit of U2 snRNP auxiliary factor (U2AF). Overexpression of U2AF65 in cells transfected with a PLE-containing reporter construct resulted in the appearance of a population of mRNAs with heterogeneous poly(A) tails. However, this effect was lost following deletion of the C-terminal RNA recognition motifs (RRMs). A C-->G mutation following the AG dinucleotide in the PLE resulted in mRNA with poly(A) ranging from 25-50 nt. This reverted to a discrete, <20 nt poly(A) tail in cells expressing U2AF65. Our results suggest that U2AF modulates the function of the PLE, perhaps by facilitating the binding of another protein to the element. | 10.1093/nar/gkg823 |
pubmed_713_22838 | BACKGROUND
Limited evidence is available about effectiveness and choice of immunomodulating treatment modalities for toxic epidermal necrolysis (TEN).
AIMS
To compare the effectiveness of interventions to reduce mortality in patients of toxic epidermal necrolysis through network meta-analysis.
METHODS
Studies were retrieved using PubMed, Google Scholar and Cochrane Database of Systematic Reviews from inception to September 18, 2018. Only English language articles were considered. Observational and randomized controlled studies having ≥ 5 TEN patients in each intervention arm were included. Two investigators independently extracted study characteristics, intervention details and mortality data. Bayesian network meta-analysis was performed using the Markov chain Monte Carlo (MCMC) approach through the random effect model. The ranking analysis was done to provide a hierarchy of interventions. The consistency between direct and indirect evidence was assessed through node spit analysis. The primary outcome was to compare the mortality [Odds ratio OR (95% credibility interval CrI)] among all treatment modalities of TEN.
RESULTS
Twenty-four studies satisfying the selection criteria were included. The network analysis showed improved survival with cyclosporine as compared to supportive care [OR- 0.19 (95% CrI: 0.05, 0.59)] and intravenous immunoglobulin [OR- 0.21 (95% CrI: 0.05, 0.76)]. The hierarchy of treatments based on "surface under the cumulative ranking curves" (SUCRA) value were cyclosporine (0.93), steroid+intravenous immunoglobulin (0.76), etanercept (0.59), steroids (0.46), intravenous immunoglobulin (0.40), supportive care (0.34) and thalidomide (0.02). No inconsistencies between direct and indirect estimates were observed for any of the treatment pairs.
LIMITATIONS
Evidence is mainly based on retrospective studies.
CONCLUSION
The use of cyclosporine can reduce mortality in TEN patients. Other promising immunomodulators could be steroid+intravenous immunoglobulin combination and etanercept. | pubmed_713_22838 |
pubmed_733_5036 | Stimulation of human colon cancer cells with insulin-like growth factor 1 (IGF-1) induces expression of the VEGF gene, encoding vascular endothelial growth factor. In this article we demonstrate that exposure of HCT116 human colon carcinoma cells to IGF-1 induces the expression of HIF-1 alpha, the regulated subunit of hypoxia-inducible factor 1, a known transactivator of the VEGF gene. In contrast to hypoxia, which induces HIF-1 alpha expression by inhibiting its ubiquitination and degradation, IGF-1 did not inhibit these processes, indicating an effect on HIF-1 alpha protein synthesis. IGF-1 stimulation of HIF-1 alpha protein and VEGF mRNA expression was inhibited by treating cells with inhibitors of phosphatidylinositol 3-kinase and MAP kinase signaling pathways. These inhibitors also blocked the IGF-1-induced phosphorylation of the translational regulatory proteins 4E-BP1, p70 S6 kinase, and eIF-4E, thus providing a mechanism for the modulation of HIF-1 alpha protein synthesis. Forced expression of a constitutively active form of the MAP kinase kinase, MEK2, was sufficient to induce HIF-1 alpha protein and VEGF mRNA expression. Involvement of the MAP kinase pathway represents a novel mechanism for the induction of HIF-1 alpha protein expression in human cancer cells. | 10.1074/jbc.M203781200 |
pubmed_317_8750 | The guidelines on the indications for gastric lavage were published in 1997, and a less-aggressive initial approach has been used for poisoned patients. Clinical studies have shown that the outcomes of retrieval of residual toxic substances in the stomach are variable and that no beneficial effect is obtained. However, the presence of residual toxic substances in the stomach before gastric lavage has not been estimated. The objective of this study was to evaluate the residual stomach contents on admission of patients with oral drug overdoses using upper gastrointestinal endoscopy. A 2-year prospective study of 167 patients with oral drug overdoses was performed. Endoscopy was performed on admission to observe the gastric body, fornix, and pyloric antrum. Patients were classified into 3 groups according to the digestive phase (tablet/food phase, soluble/fluid phase, and reticular/empty phase). The groups were compared with respect to time elapsed since ingestion, and numbers and variety of orally overdosed drugs. The numbers of patients in each phase were as follows: tablet/food phase, 73; soluble/fluid phase, 50; and reticular/empty phase, 44. The tablet/food and soluble/fluid phase groups contained the greatest numbers of patients who presented within 1 to 2 hours since ingestion. In the tablet/food group, only 12 of 73 patients (16%) presented within 1 hour since ingestion, and 3 patients presented >12 hours since ingestion. In the soluble/fluid phase group, only 9 of 50 patients (18%) presented within 1 hour since ingestion, and 2 patients presented >12 hours since ingestion. The reticular/empty phase group contained the greatest number of patients presenting within 2 to 4 hours since ingestion, and 3 patients presented within 1 hour since ingestion. The residual stomach contents before lavage were variable in all of the groups. The residual gastric content before the performance of gastric lavage is variable in overdosed patients on admission. This may influence the efficiency of gastric lavage with respect to retrieval of residual toxic substances in the stomach. This study may contribute to the development of a strategy for treating patients who have orally overdosed on drugs in the future. | 10.1097/MD.0000000000000463 |
pubmed_125_15267 | Several measures have been developed in the past decades to assess the dimensions of hardiness in adult populations, whereas the same for children has remained relatively understudied. The present research has sought to develop and validate children's hardiness scale (CHS) to assess hardiness attitudes in the respondents with age categories ranging between 10 and 12. Relying on a mixed-method approach, the research has been conducted in two studies. In the first, using both deductive and inductive methods, items were generated. The Content and face validity of the items was explored. To determine factor structure afterward, the exploratory factor analysis was conducted. In the course of the second study, confirmatory factor analysis confirmed the scale's dimensionality and factor structure. The significant correlation between CHS, academic hardiness, and perceived stress, demonstrated the construct validity of the scale. Using the convenience sampling method, a total sample of 641 children participated in both studies. The results demonstrated that the final scale in line with the hardiness theory comprised three subscales: "commitment", "control", and "challenge". The scale revealed acceptable internal consistency, reliability, and construct validity. Overall, the results of the current research indicated that a 20-item CHS can be applied in evaluating children's hardiness attitudes. Further studies are required, however, to assess the applicability of the scale in different cultural populations. | 10.1177/0033294120945175 |
pubmed_118_9651 | Splanchnic vein thrombosis (SVT) is one of the vascular complications of myeloproliferative neoplasms (MPN). We designed a phase 2 clinical trial to evaluate safety and efficacy of ruxolitinib in reducing splenomegaly and improving disease-related symptoms in patients with MPN-associated SVT. Patients diagnosed with myelofibrosis (12 cases), polycythemia vera (5 cases) and essential thrombocythemia (4 cases) received ruxolitinib for 24 weeks in the core study period. Spleen volume was assessed by magnetic resonance imaging (MRI) and splanchnic vein circulation by echo-Doppler analysis. Nineteen patients carried JAK2V617F, one had MPLW515L, and one CALRL367fs*46 mutation. Eighteen patients had spleno-portal-mesenteric thrombosis, two had Budd-Chiari syndrome, and one had both sites involved; 16 patients had esophageal varices. Ruxolitinib was well tolerated with hematological toxicities consistent with those of patients without SVT and no hemorrhagic adverse events were recorded. After 24 weeks of treatment, spleen volume reduction ≥35% by MRI was achieved by 6/21 (29%) patients, and a ≥50% spleen length reduction by palpation at any time up to week 24 was obtained by 13/21 (62%) patients. At week 72, 8 of the 13 (62%) patients maintained the spleen response by palpation. No significant effect of treatment on esophageal varices or in splanchnic circulation was observed. MPN-related symptoms, evaluated by MPN-symptom assessment form (SAF) TSS questionnaire, improved significantly during the first 4 weeks and remained stable up to week 24. In conclusion, this trial shows that ruxolitinib is safe in patients with MPN-associated SVT, and effective in reducing spleen size and disease-related symptoms. | 10.1002/ajh.24614 |
pubmed_719_3789 | The Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in 2012 during the first Middle East respiratory syndrome (MERS) outbreaks. MERS-CoV causes an acute lower-respiratory infection in humans, with a fatality rate of ~35.5%. Currently, there are no registered vaccines or means of therapeutic protection against MERS in the world. The MERS-CoV S glycoprotein plays the most important role in the viral life cycle (virus internalization). The S protein is an immunodominant antigen and the main target for neutralizing antibodies. In the present study, the immunogenicities of five different forms of the MERS-CoV S glycoprotein were compared: the full-length S glycoprotein, the full-length S glycoprotein with the transmembrane domain of the G glycoprotein of VSV (S-G), the receptor-binding domain (RBD) of the S glycoprotein, the membrane-fused RBD (the RBD fused with the transmembrane domain of the VSV G glycoprotein (RBD-G)), and the RBD fused with Fc of human IgG1 (RBD-Fc). Recombinant vectors based on human adenoviruses type 5 (rAd5) were used as delivery vehicles. Vaccination with all of the developed rAd5 vectors elicited a balanced Th1/Th2 response in mice. The most robust humoral immune response was induced after the animal had been vaccinated with the membrane-fused RBD (rAd5-RBD-G). Only immunization with membrane forms of the glycoprotein (rAd5-S, rAd5-S-G, and rAd5-RBD-G) elicited neutralizing antibodies among all vaccinated animals. The most significant cellular immune response was induced after vaccination of the animals with the full-length S (rAd5-S). These investigations suggest that the full-length S and the membrane form of the RBD (RBD-G) are the most promising vaccine candidates among all the studied forms of S glycoprotein. | pubmed_719_3789 |
pubmed_888_24050 | The proliferation and hypertrophy of growth plate chondrocytes set the pace and pattern for growth of endochondral bones. Complex signaling pathways regulating chondrocyte differentiation during development and growth have been discovered in recent years, but as yet little is known about how chondrocytes are able to orient themselves to align properly with respect to the direction of bone growth. Histomorphometric methods developed for analysis of growth plates rely to a significant extent on assessments of the relative heights of the zones of proliferating and hypertrophic chondrocytes. In a growing number of osteopetrotic mutations, however, it is becoming apparent that growth plates lack clearly demarcated zones of chondrocyte differentiation, and they show other notable histological abnormalities that cannot be measured with standard approaches. This is particularly true of mutations in which osteoclasts are altogether absent. We therefore developed a new approach that measures the salient features of this type of chondrodysplasia and have applied it to the toothless (tl) rat. The tl rat has a frameshift mutation in the Csf-1 gene that renders it null, resulting in severe osteopetrosis. An accompanying pathology is a severe, progressive growth plate chondrodysplasia. We measured cell orientation, cell area, and local columnar organization as functions of distance from the upper margin of the growth plate, in addition to growth plate thickness and cell density. All these parameters were markedly abnormal in the tl rats, thus implicating Csf-1 not only in its well-established role in regulating osteoclastic bone resorption, but also in endochondral ossification. This approach should prove useful in distinguishing among growth plate chondrodysplasias, most especially in the growing number of osteopetrotic mutations having growth plates that lack the normal zonal organization and in which the chondrocytes are mis-oriented. In turn, detailed assessments of chondrocyte misorientation may give insights into how they normally are able to arrange themselves with such precision. | 10.1080/03008200490278016 |
pubmed_1023_9803 | Ischemia of the rat small intestine lasting 40 min leads to pronounced structural disorders in lipid transport across the enterocytes, reduction in enzymatic activity of the cells and in absorption function, and to the loss of fat with feces. The normalization of the indicated parameters occurs at varying times and ends after 1 month. Fat transport abnormality is marked by an increase in lipid drops in the cavities of the smooth endoplasmic network, appearance of large and numerous matrix lipids, by a greater reduction, as compared to normal, in the membranes of the rough endoplasmic network and lamellar complex in the epithelium of the villi. Accumulation of lipids and retardation of their release from the cytoplasm are determined by incomplete differentiation of the epithelium, which is also combined with a decreased enzymatic activity. | pubmed_1023_9803 |
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