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pubmed_505_7013
In the environment horizontal DNA transfer between various bacterial species and genera takes place by transformation, transduction, but mainly by conjugation. Conjugation is responsible for the spread of genes coding for antibiotic resistance and xenobiotic degradation. Transfer events are reported in animal, rhizosphere and phylloplane ecosystems and in non polluted and polluted water and soil. Genetic exchange between Bacteria and Archaea is also observed. Evaluation of the extent of interspecies gene transfer is crucial in view of the deliberate release of a variety of unmodified and genetically modified microorganisms into the natural environments.
pubmed_505_7013
pubmed_202_18078
We have developed a particle-concentration fluorescence immunoassay (PCFIA) for estimating apolipoprotein (apo) B concentrations in plasma. A two-step antigen-detection system with a polyclonal antibody to apo B bound to carboxyl-polystyrene particles binds the antigen, and a fluorescein-labeled monoclonal antibody detects the bound apo B. Narrow-cut low-density lipoproteins (d = 1.03-1.05 kg/L) were used as the primary standard. The assay compares well with the enzyme-linked immunosorbent assay. The PCFIA gives parallel responses with low-density lipoprotein, very-low-density lipoproteins, and plasma samples, and can be fully automated and completed in 3 h. In a pilot study of patients with diabetes, coronary artery disease (CAD), or both, we found statistically significant differences in apo B concentrations for patients with both CAD and diabetes compared with those for patients with diabetes alone or for control subjects (P < 0.01).
pubmed_202_18078
pubmed_616_1166
Chaperone-mediated autophagy (CMA) is one of the main pathways of the lysosome-autophagy proteolytic system. It regulates different cellular process through the selective degradation of cytosolic proteins. In ageing, the function of CMA is impaired causing an inefficient stress response and the accumulation of damaged, oxidized or misfolded proteins, which is associated with numerous age-related diseases. Deficient protein degradation alters cellular proteostasis and activates signaling pathways that culminate in the induction of cellular senescence, whose accumulation is a typical feature of ageing. However, the relationship between CMA activity and cellular senescence has been poorly studied. Here, we review and integrate evidence showing that CMA dysfunction correlates with the acquisition of many hallmarks of cellular senescence and propose that loss of CMA function during aging promotes cellular senescence.
10.1016/j.arr.2017.11.001
pubmed_836_8439
Endogenous ouabain changes rapidly in humans and dogs upon physical exercise and is under the control of epinephrine and angiotensin II. Hence, the steroid acts as a rapidly acting hormone. A search for a specific binding globulin for cardiac glycosides in bovine plasma resulted in the identification of the d allotype of the micro chain of IgM whose hydrophobic surfaces interact with cardiotonic steroids and cholesterol. Such IgM complexes might be involved in the hepatic elimination of cardiotonic steroids. Thus, differences in the signaling cascade starting at Na(+),K(+)-ATPase must explain any differences in the action of ouabain and digoxin in the genesis of arterial hypertension.
10.1111/j.1749-6632.2003.tb07282.x
pubmed_407_13134
PURPOSE Decision-making on adjuvant radioactive iodine (RAI) treatment for early-stage papillary thyroid cancer (PTC) is complex because of uncertainties in medical evidence. Using a parallel, two-arm, randomized, controlled trial design, we examined the impact of a patient-directed computerized decision aid (DA) on the medical knowledge and decisional conflict in patients with early-stage PTC considering the choice of being treated with adjuvant RAI or not. The DA describes the rationale, possible risks and benefits, and the medical evidence uncertainty relating to the choice. PATIENTS AND METHODS We recruited 74 patients with early-stage PTC after thyroidectomy. Participants were assigned by using 1:1 central computerized randomization to either the DA group with usual care (intervention) or usual care alone (control). Medical knowledge about PTC and RAI treatment (the primary outcome), as well as decisional conflict (a secondary outcome), were measured by using validated questionnaires, and the respective scores were compared between groups. RESULTS Consistent with PTC epidemiology, 83.8% (62 of 74) of the participants were women, and the mean age was 45.8 years (range, 19 to 79 years). Medical knowledge about PTC and RAI treatment was significantly greater and decisional conflict was significantly reduced in the DA group compared with the control group (respective P values < .001). The use of adjuvant RAI treatment was not significantly different between groups (DA group, 11 of 37 [29.7%]; controls, seven of 37 [18.9%]; P = .278). CONCLUSION A computerized DA improves informed decision making in patients with early-stage PTC who are considering adjuvant RAI treatment. DAs are useful for patients facing decisions subject to medical evidence uncertainty.
10.1200/JCO.2011.41.2734
pubmed_95_6016
Arterial waveform configuration is an underused monitoring tool in the intensive care setting. Characteristic changes in configuration occur throughout the illness-wellness continuum for a number of disease processes. The cases presented illustrate the opportunity for preliminary diagnosis and early intervention.
10.1016/s0147-9563(97)90057-1
pubmed_196_15440
Approximately 20% of all epilepsy is caused by acute acquired injury such as traumatic brain injury, stroke and CNS infection. The known onset of the injury which triggers the epileptogenic process, early presentation to medical care, and a latency between the injury and the development of clinical epilepsy present an opportunity to intervene with treatment to prevent epilepsy. No such treatment exists and yet there has been remarkably little clinical research during the last 20 years to try to develop such treatment. We review possible reasons for this, possible ways to rectify the situations and note some of the ways currently under way to do so. Resective surgical treatment can achieve "cure" in some patients but is sparsely utilized. In certain "self-limiting" syndromes of childhood and adolescence epilepsy remits spontaneously. In a proportion of patients who become seizure free on medications or with dietary treatment, seizure freedom persists when treatment is discontinued. We discuss these situations which can be considered "cures"; and note that at present we have little understanding of mechanism of such cures, and cannot therefore translate them into a treatment paradigm targeting a "cure" of epilepsy. This article is part of the special issue entitled 'New Epilepsy Therapies for the 21st Century - From Antiseizure Drugs to Prevention, Modification and Cure of Epilepsy'.
10.1016/j.neuropharm.2019.107762
pubmed_337_3513
Current research has noted that auditory stimuli via rhythmic cues can enhance speech in patients with basal ganglia lesions. The contribution of basal ganglia function in music perception and performance is a matter of discussion. The French composer Maurice Ravel suffered from a progressive degenerative cerebral disease of uncertain etiology, probably primary progressive aphasia. Based on the case of the famous composer, we present the hypothesis that the fact he adopted different uses of timbre could be attributed to the altered basal ganglia function during the disease evolution. Our assumption would like to add a point of view to the current diagnostic debate.
10.1177/1471301216642066
pubmed_904_13300
Working together allows social animals to accomplish tasks beyond the abilities of solitary individuals, but the benefits of cooperation must be balanced with the costs of coordination. Many ant species form cooperative groups to transport items too large for a single ant. However, transport by groups is often slower and less efficient than that of lone ants, for reasons that remain poorly understood. We tested the hypothesis that groups are slower when porters must encircle the load to carry it, because this arrangement places ants in a variety of postures relative to the load and the direction of travel. Porters may therefore have difficulty maximizing individual forces and aligning them with those of other group members. Experiments on the desert ant Novomessor cockerelli, an adept cooperative transporter, did not support this hypothesis. Groups ranging in size from one to four ants were induced to carry loads such that all porters were aligned with one another. Load weight was adjusted so that all porters pulled the same per capita weight, but lone porters were nonetheless faster than groups of any size. As group size increased, porters persisted in carrying the load for longer periods before letting go. We used simulations to explore a scenario in which ants vary in their intrinsic speed and the group's speed is limited by that of its slowest member. This proposed mechanism is analogous to other social groups where group efficiency is determined by the weakest link. We discuss how interactions among porters, mediated by the load itself, might explain such a constraint.
10.1371/journal.pone.0205400
pubmed_186_20736
BACKGROUND Scleroderma is an antigen-driven T cell-mediated autoimmune disease. Presence of anti-topoisomerase-I antibodies is associated with pulmonary fibrosis and predicts increased mortality. Characterization of autoreactive T lymphocytes may shed light on disease pathogenesis and serve as a biomarker for disease activity. Here, we aimed to quantify and functionally characterize circulating topoisomerase I (topo-I)-specific CD4+ T cells and to define their association with presence and progression of interstitial lung disease (ILD) in patients with scleroderma. METHODS Using flow cytometry, circulating topo-I-reactive CD4+ T cells were identified by the expression of specific activation markers (CD154 and CD69) upon stimulation with purified topo-I and quantified in 27 SSc patients and 4 healthy donors (HD). Polarization of autoreactive T cells (Th1, Th2, Th17, Th1-17) was defined using surface expression of specific chemokine receptors. Presence and progression of ILD were determined using high-resolution chest CT and pulmonary function tests. RESULTS Topo-I-reactive CD4+ T cells were found in all topo-I-positive patients compared to one topo-I-negative subject and no HD. Topo-I-specific CD4+ T cells exhibited a distinct Th17 polarized phenotype. Autoreactive T cells were significantly increased in subjects with evidence of ILD and were quantitatively associated with the decline of lung volumes. CONCLUSIONS Topo-I-specific T cells can be reliably quantified in the peripheral blood of patients with scleroderma, exhibit a pro-inflammatory Th17 phenotype, and predict progression of ILD.
10.1186/s13075-016-0993-2
pubmed_354_16540
In foie gras production the technological yield after the cooking process is one of the main issues of processors as it is closely linked to the cooking melting rate. This rate is subjected to strict laws and regulations since it directly affects the organoleptic and technological qualities of this gourmet product. The objective of the study was to better understand the liver fattening and the technological yield decrease during the overfeeding kinetics. A flock of 210 mule ducks was reared and then overfed during 12 D with 2 overfeeding programs; in the test group the amounts of corn in the first meals were higher than in the control group (+430 g during the whole period). Ducks were slaughtered at the end of the rearing period (D0, n = 15) and every other day (D2 to D12, n = 15 by group). Duck performances, anatomical dissections and physical and biochemical liver characteristics were registered. The performances were equivalent in the groups (P > 0.1). The evolution of the liver weight was then analyzed in detail in relation with the evolution of its biochemical composition. A two-step evolution occurred in the liver metabolism, first a main glycogen storage and then a strong lipid storage. A model to predict the liver weight was established with only BWs and feed intakes (R² = 0.83). The technological yield was determined on foie gras weighing more than 300 g (D6 to D12). The melting process was high during the last 2 D. The technological yield reached 72% at D12, for 758 g foie gras, and a strong negative correlation was observed with liver weight (-0.83; P < 0.001). A model to predict the technological yield was established with the liver weight and the liver color parameters (R² = 0.71). This study highlights the compromise between foie gras weight and its quality.
10.3382/ps/pez359
pubmed_137_9607
Neurorehabilitation and brain stimulation studies of post-stroke patients suggest that action-observation effects can lead to rapid improvements in the recovery of motor functions and long-term motor cortical reorganization. Apraxia is a clinically important disorder characterized by marked impairment in representing and performing skillful movements [gestures], which limits many daily activities and impedes independent functioning. Recent clinical research has revealed errors of visuo-motor integration in patients with apraxia. This paper presents a rehabilitative perspective focusing on the possibility of action observation as a therapeutic treatment for patients with apraxia. This perspective also outlines impacts on neurorehabilitation and brain repair following the reinforcement of the perceptual-motor coupling. To date, interventions based primarily on action observation in apraxia have not been undertaken.
10.3389/fneur.2019.00309
pubmed_391_9654
Evidence that calcium antagonists can suppress diet-induced atherosclerosis in the thoracic aorta of animals has existed for a decade. Recently, the results of quantitative angiographic trials of calcium antagonists in humans have become available, confirming their beneficial effect on coronary artery disease. Nifedipine treatment reduces the rate of new lesion development in patients with mild-to-moderate coronary artery disease, reduces disease progression, and, in some cases, induces lesion regression. There is evidence that the use of verapamil may be associated with lesion regression and stenosis prevention, and that nicardipine may influence the progression of minimal coronary lesions. Theoretically, a wide range of explanations for an effect of calcium antagonists on atherogenesis is possible. Potential mechanisms include preventing calcium overload, upregulating LDL receptors with enhanced LDL clearance, inhibiting cell migration into the arterial wall, and antiplatelet effects. The exact mechanism remains unclear, but alteration of serum lipid levels and blood pressure does not appear to be the common pathway. Work with humans is still preliminary, and longer follow-up and further trials are required to determine the appropriate clinical application of calcium timing for their introduction.
10.1093/ajh/4.7.512s
pubmed_613_12249
Currently available models describing microbial fuel cell (MFC) polarization curves, do not describe the effect of the presence of toxic components. A bioelectrochemical model combined with enzyme inhibition kinetics, that describes the polarization curve of an MFC-based biosensor, was modified to describe four types of toxicity. To get a stable and sensitive sensor, the overpotential has to be controlled. Simulations with the four modified models were performed to predict the overpotential that gives the most sensitive sensor. These simulations were based on data and parameter values from experimental results under non-toxic conditions. Given the parameter values from experimental results, controlling the overpotential at 250 mV leads to a sensor that is most sensitive to components that influence the whole bacterial metabolism or that influence the substrate affinity constant (Km). Controlling the overpotential at 105 mV is the most sensitive setting for components influencing the ratio of biochemical over electrochemical reaction rate constants (K1), while an overpotential of 76 mV gives the most sensitive setting for components that influence the ratio of the forward over backward biochemical rate constants (K2). The sensitivity of the biosensor was also analyzed for robustness against changes in the model parameters other than toxicity. As an example, the tradeoff between sensitivity and robustness for the model describing changes on K1 (IK1) is presented. The biosensor is sensitive for toxic components and robust for changes in model parameter K2 when overpotential is controlled between 118 and 140 mV under the simulated conditions.
10.1016/j.bios.2010.11.049
pubmed_748_13560
BACKGROUND Increased detection of nodular lesions that have not yet been definitively diagnosed as hepatocellular carcinoma (HCC) has occurred with the use of advanced imaging techniques. In heavy drinkers, the differential diagnosis between a hyperplastic nodule and early HCC on the basis of results of fine-needle biopsy is often difficult. Negation of diagnosis of HCC after surgical resection has been reported, and nodular lesions have been found to decrease during follow-up observation. On the basis of findings, a suitable strategy for the management of such lesions is suggested. METHODS We identified six patients who had hepatic nodular lesions on ultrasonography and were heavy drinkers. This group included five men and one woman with a mean age of 45.3 +/- 3.8 years. Two patients had solitary lesions; four had multiple lesions, and of these, two were hepatitis C virus antibody positive (C+). In the five men, the nodular lesions were detected during hospitalization for ruptured or prophylactic treatment of gastroesophageal varices. RESULTS Five of the six patients had hypervascular lesions characterized by increased hepatic artery blood flow. However, dynamic computed tomography and magnetic resonance imaging studies during late-phase imaging could not confirm any decrease in portal blood flow. HCC was diagnosed by detailed imaging studies and liver biopsy in one C+ patient with a solitary nodule. In two of the other four patients, imaging findings were compatible with hypervascular HCC. Findings on liver biopsy do not always permit an easy differential diagnosis between a regenerative lesion (hyperplastic nodule) and a dysplastic or neoplastic lesion. One patient with a hypovascular lesion was C+, and liver biopsy showed a dysplastic nodule. CONCLUSION Heavy drinkers with alcoholic liver disease often develop hypervascular, hyperplastic nodules. The accurate diagnosis of these nodules requires careful consideration of clinical factors, including a combination of images and histologic examination. However, some cases were still difficult to distinguish between HCC by applying advanced imaging techniques and biopsy results.
10.1097/01.alc.0000134414.00009.a7
pubmed_1055_4063
A s many as 70 per cent of the / I nurses who leave the UK for the United States apply fora'green w 1 card', or permanent work permit once their temporary visas expire.
10.7748/ns.2.50.68.s98
pubmed_1136_9951
Molecular dynamics simulations are performed to study the physical mechanism of cobra cardiotoxin (CTX) proteins adsorption on alkanethiol self-assembled monolayers (SAMs) composed of S(CH(2))(5)CH(3) and S(CH(2))(9)CH(3). The binding energy of the CTX protein to the SAM surface of different mixing ratios of alkanethiol chains is calculated. The results show that the affinity of CTX to SAM reaches a maximum value when the ratio S(CH(2))(5)CH(3):S(CH(2))(9)CH(3) is 1:1, which agrees with the measurements of atomic force microscope obtained in Part I of our dual paper. Moreover, the binding energy is found to be linearly proportional to the CTX-SAM contact area. The hydrophobicity on CTX residues, the flexibility of SAMs and the behavior of water molecules near the SAM surface are examined to understand how these parameters affect the adsorption of a CTX protein on SAM surfaces. In addition, the importance of modeling water molecules explicitly in the study of protein adsorption is demonstrated by applying different solvent models.
10.1109/TNB.2010.2070517
pubmed_542_12816
When coated vesicles (CVs) are incubated with [gamma-32P]ATP, radioactivity is rapidly incorporated into a compound identified by thin layer chromatography as phosphatidylinositol 4-phosphate. This activity has been identified in CVs isolated from bovine brain as well as from rat liver and chick embryo skeletal muscle. Phosphatidylinositol (PI) kinase is not separated from CVs during agarose electrophoresis, which produces CVs of greater than 95% purity, indicating that the activity present does not derive from contamination. The specific activity of these highly purified CVs was demonstrated to be approximately twice that of synaptic plasma membranes, further ruling out contamination from this source. The PI kinase remains associated with the vesicle upon removal of clathrin and its associated proteins and is solubilized by nonionic detergents, suggesting it is an integral membrane protein. We have been unable to demonstrate the formation of significant amounts of phosphatidylinositol 4,5-bisphosphate in any of our CV preparations. In the presence of exogenous PI, activity is stimulated, with maximal phosphorylation occurring at 0.1 mM. The enzyme appears to be maximally stimulated by 200 mM MgCl2 and 1 mM ATP and is most active at pH 7.25. Calculations indicate that, under optimal conditions, approximately 25 molecules of PIP are produced per CV within 60 s, suggesting that these structures may play an important role in cellular PI metabolism.
pubmed_542_12816
pubmed_602_1417
BACKGROUND Improved immunosuppressive regimens and management strategies in renal transplantation (RT) have increased patient and graft survival during the last years. The aim of our study was to analyze the causes, risk factors, and evolution of mortality after renal transplantation. METHODS We studied 3365 renal transplant recipients in adults (>18 years) who survived at least 1 year after transplantation in Spain during 1990, 1994, and 1998. The mortality rates and risk factors were analyzed employing single and multivariate Cox regression. RESULTS The follow-up was shortest (maximum 2.5 years) for recipients transplanted in 1998. When we consider an identical follow-up period (2.5 years) for all patients, we did not observe a statistical difference in patient survival and causes of death in the three analyzed periods. Mortality was higher for men and for patients over 60 years. Cardiovascular diseases (CVD) and neoplasia were the most frequent causes of death. Graft dysfunction, as determined by creatinine level or proteinuria range in the first months, were significant factors associated with a higher risk for cardiovascular and infectious deaths. CONCLUSIONS During the last decade in Spain, patient survival after RT (2.5 years follow-up) has remained stable. Recipient age (>60 years), male gender, and graft dysfunction in the first year were associated with a higher risk of death especially due to CVD.
10.1016/j.transproceed.2004.03.038
pubmed_762_17894
A total of 713 strains of fecal Escherichia coli (E. coli) isolated from laboratory animals in the colonies of 4 research laboratories and 4 commercial breeders in Japan in 1994 were examined in regard to resistance to 8 antibacterial agents. The incidence of resistance to sulfadimethoxine (Su), streptomycin (Sm), ampicillin, cephaloridine, tetracycline, chloramphenicol, kanamycin, and gentamicin was 99.9%, 32.5%, 6.7%, 0.7%, 7.0%, 2.6%, 6.6% and 0.7%, respectively. These results indicated that Su and Sm resistance are penetrating into normal E. coli strains isolated from laboratory animals.
10.1292/jvms.64.1133
pubmed_347_1179
The bacterial ribosomal protein S12 contains a universally conserved D88 residue on a loop region thought to be critically involved in translation due to its proximal location to the A site of the 30S subunit. While D88 mutants are lethal this residue has been found to be post-translationally modified to β-methylthioaspartic acid, a post-translational modification (PTM) identified in S12 orthologs from several phylogenetically distinct bacteria. In a previous report focused on characterizing this PTM, our results provided evidence that this conserved loop region might be involved in forming multiple proteins-protein interactions ( Strader , M. B. ; Costantino , N. ; Elkins , C. A. ; Chen , C. Y. ; Patel , I. ; Makusky , A. J. ; Choy , J. S. ; Court , D. L. ; Markey , S. P. ; Kowalak , J. A. A proteomic and transcriptomic approach reveals new insight into betamethylthiolation of Escherichia coli ribosomal protein S12. Mol. Cell. Proteomics 2011 , 10 , M110 005199 ). To follow-up on this study, the D88 containing loop was probed to identify candidate binders employing a two-step complementary affinity purification strategy. The first involved an endogenously expressed S12 protein containing a C-terminal tag for capturing S12 binding partners. The second strategy utilized a synthetic biotinylated peptide representing the D88 conserved loop region for capturing S12 loop interaction partners. Captured proteins from both approaches were detected by utilizing SDS-PAGE and one-dimensional liquid chromatography-tandem mass spectrometry. The results presented in this report revealed proteins that form direct interactions with the 30S subunit and elucidated which are likely to interact with S12. In addition, we provide evidence that two proteins involved in regulating ribosome and/or mRNA transcript levels under stress conditions, RNase R and Hfq, form direct interactions with the S12 conserved loop, suggesting that it is likely part of a protein binding interface.
10.1021/pr3009435
pubmed_633_6514
The alveolar bone loss is a phenomenon which intervenes throughout the life and which can be aggravated by the action of individual and behavioural factors. From this observation we shall try to characterize it and to propose formulas of prediction of the alveolar bone loss according to the age of the patient. We shall expose an analysis of factors bound to the alveolar bone loss and propose a modeling of the alveolar bone loss according to the age in an essentially predictive purpose. The methodology is based on the medical exploitation of CT-dentascanners and medical questionnaire as well as administrative questionnaire used in odontology. Measures of the distance ECJ and the summit of crest are made on the radiology and the individual factors and behavioural factors are scored. The descriptive analysis of the data allowed us to characterize the phenomenon of alveolar bone loss in a therapeutic purpose. The statistical treatment of these data will establish various models according to gender. The described method is simple and its applications seem numerous in the several domains: prevention, improvement of prosthetic and periodontal therapeutics.
pubmed_633_6514
pubmed_320_9288
Winds in the lower atmosphere of Venus, inferred from three-dimensional radio interferometric tracking of the descents of the Pioneer day and north probes, are predominantly easterly with speeds of about 1 meter per second near the surface, 50 meters per second at the bottom of the clouds, and more than 200 meters per second within the densest, middle cloud layer. Between about 25 and 55 kilometers altitude the average flow was slanted equatorward, with superimposed wavelike motions and alternating layers of high and low shear.
10.1126/science.205.4401.85
pubmed_794_6031
RATIONALE Primary ovarian abscess which develops as an isolated lesion without simultaneous tubal infection is a rare entity. Ovarian abscess (OA) is a serious complication of pelvic inflammatory disease (PID) rarely seen in virginal girls. Early diagnosis and treatment are essential to prevent further sequela including infertility, ectopic pregnancy, and chronic pelvic pain. PATIENT CONCERNS A 19-year-old virginal girl who presented with abdominal pain and pelvic mass with no risk factors. DIAGNOSES Laparoscopic surgery was performed to confirm a primary ovarian abscess in the adolescent virginal female with a huge endometriosis cyst. INTERVENTION Ovarian abscess with extensive intestinal adhesions was determined during the laparoscopic operation. Abscess drainage and postoperative antibiotic therapy cured the patient. OUTCOME After the surgery, the CRP level on the day of discharge was 3.18 mg/d. The histological findings revealed a cystic tissue sample with the fibrous wall infiltrated by neutrophilic granulocytes, and ectopic endometrium, suggesting abscess formation in the ovary and endometriosis cyst. LESSONS Although primary ovarian abscess in an adolescent virginal female is rare, given the severity of outcomes following ovarian abscess, this pathology should be considered in the differential diagnosis of virginal adolescents with fever and abdominal pain.
10.1097/MD.0000000000029463
pubmed_663_7730
Membrane nanotubes were recently described as a new principle of cell-cell communication enabling complex and specific messaging to distant cells. Calcium fluxes, vesicles, and cell-surface components can all traffic between cells connected by nanotubes. Here we report for the first time the mechanism of membrane nanotube formation in T cells through LFA-1 (CD11a/CD18; alpha(L)beta(2)) integrin activation by the cysteine protease cathepsin X. Cathepsin X is shown to induce persistent LFA-1 activation. Cathepsin X-upregulated T cells exhibit increased homotypic aggregation and polarized, migration-associated morphology in 2D and 3D models, respectively. In these cells, extended uropods are frequently formed, which subsequently elongate to nanotubes connecting T lymphocytes. Our results demonstrate that LFA-1 activation with subsequent cytoskeletal reorganization induces signal transmission through a physically connected network of T lymphocytes for better coordination of their action at various stages of the immune response.
10.1007/s00018-009-8829-8
pubmed_899_20984
OBJECTIVE To evaluate the effect of N-benzyl-4-bromobenzamide (NBBA) on lipopolysaccharide (LPS)-induced IL-6 and prostaglandin E2 (PGE2) production in human gingival fibroblasts (HGFs). MATERIAL AND METHODS The benzamide compound was synthesized. The condition for IL-6 production of HGFs after induction with LPS was optimized. The HGFs were incubated with NBBA (10 µg/ml) for 30 min before LPS (1 μg/ml) was added. After 24 h of incubation time, the culture media were harvested and their IL-6 and PGE2 contents were determined using an enzyme-linked immunosorbent assay. Prednisolone (PDS) and NS-398 were used as positive controls. Statistical analysis of the IL-6 and PGE2 contents was performed using the ANOVA test followed by the Tukey multiple-comparisons test to compare replicate means. p < 0.001 was considered statistically significant. RESULTS The maximum IL-6 production was achieved when HGFs were exposed to 1 μg/ml of LPS for 24 h, which was inhibited by the IL-6 immunosuppressant PDS. The benzamide compound, NBBA, exhibited a potent anti-IL-6 activity with inhibition of 35.6 ± 0.5%, significantly different from in the LPS-induced HGFs (p < 0.001). In addition, it inhibited 75.6 ± 0.52% PGE2 production. Cell viability was not significantly affected by treatment with NBBA at a concentration <10 µg/ml (p < 0.001). CONCLUSIONS NBBA exhibited an inhibitory effect on the production of IL-6 and PGE2 in LPS-induced HGFs. It could serve as a compound with inhibiting inflammatory activity in periodontal disease.
10.1159/000442164
pubmed_890_20910
The purpose of this study was to evaluate risk factors for failure of antibiotic treatment within 30 days for uncomplicated skin infections of outpatients treated in a Veterans Affairs hospital. A retrospective chart review of outpatients between January 2006 and July 2015 with an ICD-9 (International Statistical Classification of Diseases and Related Health Problems) code of cellulitis or abscess was included in the analysis. The primary outcome was success versus failure of the antibiotic, with failure defined as another antibiotic prescribed or hospitalization within 30 days for the original indication. A total of 293 patients were included in the final analysis, 24% of whom failed within 30 days. Obesity/overweight (body mass index [BMI] of >25 kg/m2) was identified in 83% of the overall population, with 16% of that population having a BMI greater than 40 kg/m2 An elevated mean BMI of 34.2 kg/m2 (P = 0.0098) was found in the subset of patients who failed oral antibiotics compared to a BMI of 31.32 kg/m2 in patients who were treated successfully. Additionally, the patients who failed had an increased prevalence of heart failure at 16% (P = 0.027). Using multivariate logistic regression, BMI and heart failure were determined to be significant predictors of antibiotic prescription failure. Each 10-kg/m2 unit increase in BMI was associated with a 1.62-fold-greater odds of failure. A diagnosis of heart failure increased the odds of failure by 2.6-fold (range, 1.1- to 5.8-fold). Outpatients with uncomplicated skin infections with an elevated BMI and heart failure were found to have increased odds of failure, defined as hospitalization or additional antibiotics within 30 days.
10.1128/AAC.02389-16
pubmed_266_24781
OBJECTIVES The purpose of this study was to define anterior mitral leaflet (AML) length and mitral ring characteristics associated with LVOT obstruction and PVL following MViR. BACKGROUND Transcatheter Mitral Valve in Ring (MViR) procedural complications including parvalvular leak (PVL) and left ventricular outflow tract (LVOT) obstruction are frequent. METHODS Clinical records, computer tomographic scans (CTs) and echocardiograms of consecutive MViR patients were retrospectively reviewed for anterior mitral leaflet length, CT-simulated neoLVOT, and aortomitral angle among patients with and without MViR-induced LVOT obstruction. Acute and 1-year outcomes are described. RESULTS Twenty-two patients underwent MViR. Technical success was achieved in 13/22 (57.1%) patients, limited by paravalvular regurgitation requiring second transcatheter heart valves (THVs) in seven patients. Second valves were needed in 6/11 (54.5%) patients with 3-dimensional rings but 1/11 (9.1%, p = .06) of patients with planar rings. Procedure success at 30 days was achieved in 20/22 (90.9%) patients. There were no procedural, in-hospital, or 30-day deaths. Two patients developed significant LVOT obstruction, one managed with urgent surgery and one with elective alcohol septal ablation. Anterior mitral leaflets were longer among the two patients with LVOT obstruction than the 20 patients who did not develop LVOT obstruction when measured by TEE (30 mm vs. 21 mm, p = .009) or by CT (29 mm vs. 22 mm, p = .026). CONCLUSIONS AML >25 mm increases the risk of MViR induced LVOT obstruction. PVL is common, particularly in 3-dimensional rings which can be managed with a second THV.
10.1002/ccd.29232
pubmed_369_20126
Chimeric T cell receptors (chTCRs), composed of the single-chain variable fragments (scFv) of murine antibodies and human signaling molecules, are used to redirect the specificity of autologous or allogeneic T lymphocytes. To develop novel therapeutic agents for treatment of chronic myeloid leukemia (CML), we engineered a scFv from the hybridoma cell line CMA1 which produces monoclonal antibody specific against CML. The genes encoding the heavy and light chain variable regions were amplified from CMA1 cDNA and a humanized chTCR was constructed. Expression of the novel hchTCR was verified in NIH3T3 cells transduced with retroviral vectors. The results demonstrated that hchTCR can be expressed and presented on cell surface normally. These results suggest that retroviral vectors expressing hchTCR specific for CML cells may be used to redirect human T lymphocytes.
10.1007/s10529-012-0896-5
pubmed_914_20799
General anaesthesia is an important measure in the treatment of patients suffering from organophosphorus intoxication. The intravenous anaesthetic etomidate seems to be well suited for this purpose because of its stable haemodynamics. Here we raise the question whether the anaesthetic properties of etomidate are altered by cholinergic overstimulation and by the cholinergic antagonist atropine. As the neocortex and spinal cord mediate unconsciousness and immobility, organotypic cultures from these regions were used for pharmacological in vitro studies. The effects of etomidate on spontaneous action potential activity were assessed by extracellular action potential recordings under basal cholinergic tone, in the presence of acetylcholine, and in the additional presence of atropine. Etomidate (1μM) depressed neuronal activity in cortical slices by 47.5±6.9%, but only by 24.9±16.7% in the presence of acetylcholine. If atropine (10nM) was given in addition, the depression by etomidate was restored (53.4±4.2%). Similar results were obtained using cultured slices from the spinal cord. In summary, cholinergic overstimulation decreased the ability of etomidate to depress neuronal activity in neocortex and spinal cord. Atropine reversed this decrease. Hence, etomidate is potentially applicable for induction of anaesthesia in patients suffering from severe cholinergic crisis, preconditioned that atropine is co-applied.
10.1016/j.toxlet.2010.07.016
pubmed_542_16957
UNLABELLED Tardive dyskinesia, described for the first time in 1957, have increased in frequency since neuroleptics started to be widely used. Is that disorder drug induced, or related to the psychosis, or does it exist in the general population, caused by others factors? This study is a trial in the approach of the problem. METHODOLOGY the occurrence of tardive dyskinesia was rated for three kinds of populations which are schizophrenics never treated by neuroleptics; schizophrenics under treatment by neuroleptics; general population non psychotic and never treated by neuroleptics. Diagnostic criteria of schizophrenia are DSM III ones. Abnormal Involuntary Movement Scales of NIMH have been used in this work. The percentage is 14% in schizophrenics already treated by neuroleptics, and no one in the other two groups had dyskinesia. The middle duration of the illness in the schizophrenics group was about 12 months. Those results allow us to eliminate possible spontaneous dyskinesia in the general population which is young; to suppose that there is probably no responsibility of the psychosis in this disorder, at least at the beginning of the illness; to confirm that neuroleptic medication, alone or associated with other factors, is responsible for the occurrence of tardive dyskinesia.
pubmed_542_16957
pubmed_1061_14475
Hypertension and brachydactyly syndrome (HTNB; MIM 112410) is a rare, recently described, autosomal dominant syndromic disease characterized by the triad of brachydactyly type E (BDE), short stature, and hypertension. HTNB is caused by a heterozygous mutation in the PDE3A (MIM 123805) gene on chromosome 12p12; this gene encodes a member of the cGMP-inhibited cyclic nucleotide phosphodiesterase family. PED3A plays a role in many signal transduction pathways, including those involved in vascular smooth muscle proliferation and contraction, cardiac contractility, platelet aggregation, and hormone secretion. Here, we present a new case of HTNB in a 42-year-old patient who experienced recurrent ischemic strokes in various vascular territories; these strokes were caused by intracranial multiarterial dissection, and were experienced for 2 weeks. She was found to harbor a de novo heterozygous in-frame deletion, c.1333_1335del p.(Thr445del), in exon 4 of the PDE3A gene. Our finding is expected to contribute to the elucidation of the pathophysiology of stroke in HTNB patients. We further review all clinical and molecular genetic features of this rare disease described in the literature to date.
10.1016/j.ejmg.2019.103781
pubmed_211_10856
Three constitutive gelatinases in human plasma were identified and characterized relative to known matrix metalloproteinase (MMP) gelatinases: MMP-2 (fibroblast 72-kDa) and MMP-9 (neutrophil 92-, 130-, and 225-kDa). Substrate gel electrophoresis (gelatin zymography) revealed an apparent Mw of 78-, 82-, and 89-kDa for these gelatinases. Densitometry revealed that MMP-9 and MMP-2 were highly calcium sensitive requiring 50-150 microM and 500 microM calcium for half-maximal activity, respectively. Of the new gelatinases, only the 89-kDa form demonstrated slight calcium activation. The three gelatinases were unaffected by known MMP inhibitors: EDTA (5 mM), 1,10-phenanthroline (2 mM), and pepstatin (18 microM). Serine and thiol protease inhibitors (leupeptin, aprotinin, PMSF, TLCK, TPCK, antichymostatin, antipain) were also ineffective. Solution-phase IEF revealed that the 78- and 82-kDa forms focused at neutral pI 6.72-7.95 whereas the 89-kDa focused at an acidic pI 4.89-5.18 (similar to neutrophil and fibroblast forms). The data indicate that these gelatinases are not MMPs or partially activated MMPs. Their role in normal and pathological conditions is not known.
10.1080/15216549800204592
pubmed_755_16101
Differences in rate of ATP resynthesis between apposing heart cells were created by dialysing 2-4-dinitrophenol (0.01-0.05 mM) into just one cell of isolated heart cell pairs. When 0.01 mM of dinitrophenol was used the junctional conductance (gj) remained unchanged for at least 8 min if cell 1 (normal) was pulsed at low rate (0.04 Hz). The increment in rate of pulsing to 4 Hz caused a fast decrease (13%) of gj within 30 sec. This change in gj was spontaneously reversed. With 0.05 mM of dinitrophenol cell uncoupling was produced if cell 1 (normal) was stimulated at 4 Hz for 25-30 sec. Despite the suppression of electrical coupling (which was not reversed within 8 min.) no contracture or signs of deterioration of the experimental conditions were found. Cell uncoupling can be seen as a protective mechanism providing opportunity to energy-depleted cells to re-establish their ATP stores.
10.1016/s0309-1651(06)80004-4
pubmed_761_7809
Background and Purpose- Optimal management of the extracranial occlusive component remains controversial in patients with acute ischemic stroke by tandem occlusion treated with mechanical thrombectomy. We investigated the association between extracranial internal carotid artery (ICA) patency at day 1 and the clinical outcome after mechanical thrombectomy. Methods- Consecutive patients with acute ischemic stroke with tandem occlusion were identified from a hospital-based prospective registry from 2011 to 2017. Baseline characteristics, angiographic outcomes, and day 1 ICA patency assessed by MR angiography were analyzed with regard to their associations with 3-month modified Rankin Scale scores. Favorable outcome was defined as a modified Rankin Scale score of 0 to 2 at 3 months. Results- Of 594 patients with acute ischemic stroke treated with mechanical thrombectomy during the study period, 83 met inclusion criteria. Successful recanalization (modified Thrombolysis in Cerebral Infarction, 2b/3) was achieved in 61.5%. Extracranial ICA was patent in 37 of 83 patients (44.6%) at day 1, more frequently in those with prior intravenous thrombolysis ( P=0.035) or with cervical revascularization procedure (balloon angioplasty or stenting, P=0.034). Favorable 3-month functional outcome was more frequent in patients with patent extracranial ICA at day 1 (adjusted odds ratio, 4.72; 95% CI, 1.76-13.34; P=0.003) independent of intracranial recanalization success. Conclusions- Day 1 stable extracranial ICA patency is associated with better clinical outcome in patients with acute ischemic stroke with tandem occlusions. Randomized studies are needed.
10.1161/STROKEAHA.118.022495
pubmed_214_25146
Crystalline/ionic liquid crystalline block copolymers (BCPs) with various compositions have been successfully prepared by sequential reactions. The effect of corona liquid crystalline order on self-assembly of BCPs in selective solvent is investigated in detail. It is found that two-dimensional single crystals with well-developed shapes are formed when the liquid crystalline order is present. By contrast, ill-developed platelets with small size or one-dimensional worm-like micelles are assembled if the liquid crystalline order of the corona segments is lost. It is speculated that the preferred parallel arrangement of liquid crystalline block enables it to expose more growth front of crystals. Accordingly, epitaxial crystallization will proceed readily, leading to fabrication of the well-defined single crystals.
10.1021/acsmacrolett.6b00428
pubmed_140_10999
Late life depression is an important public health problem, which associates with increased risk of morbidity and mortality. Selective serotonin reuptake inhibitors (SSRIs), including fluoxetine, are often prescribed to treat geriatric depression. There is increasing evidence that fluoxetine and other SSRIs exert a wide range of cardiovascular side effects. Furthermore, there is evidence that aging may increase plasma level of SSRIs. In this overview, the potential role of side effects of treatment with fluoxetine and other SSRIs in the pathogenesis of age-related cardiovascular diseases, including atherogenesis, cardiac pathologies, and cerebromicrovascular impairment, is discussed.
10.3389/fgene.2019.00898
pubmed_824_24631
Many researchers assume that there is a relationship between health literacy and eHealth literacy, yet it is not clear whether the literature supports this assumption. The purpose of this study was to determine if there was a relationship between health and eHealth literacy. To this end, participants' (n = 36) scores on the Newest Vital Sign (NVS, a health literacy measure) were correlated with the eHealth Literacy Scale (eHEALS, an eHealth literacy measure). This analysis revealed no relationship (r = -.041, p = .81) between the two variables. This finding suggests that eHealth Literacy and health literacy are dissimilar. Several possible explanations of the pattern of results are proposed. Currently, it does not seem prudent to use the eHEALS as the sole measure of eHealth literacy, but rather researchers should continue to complement it with a validated health literacy screening tool.
pubmed_824_24631
pubmed_402_3772
BACKGROUND Liver failure is a rare but devastating result of drug toxicity. OBJECTIVE To describe three cases of subfulminant liver failure that were probably caused by nefazodone, a new antidepressant that is a synthetically derived phenylpiperazine. DESIGN Case series. SETTING Two university medical centers and a children's hospital. PATIENTS Three women 16 to 57 years of age. INTERVENTION Two patients underwent liver transplantation; the third was listed for transplantation but subsequently improved. MEASUREMENT Liver biopsy. RESULTS Nefazodone was administered for 14 to 28 weeks before the onset of symptoms. The duration of jaundice before onset of encephalopathy ranged from 4 to 6 weeks. All cases of liver failure had similar histologic appearance, with prominent necrosis in the centrolobular areas (zone 3). One patient had successful liver transplantation, one underwent transplantation but died, and one improved without transplantation. The temporal onset of disease after the start of nefazodone therapy suggested severe hepatocellular injury caused by the drug. CONCLUSIONS Because nefazodone seems to cause severe hepatocellular injury in an idiosyncratic manner, routine liver chemistries should be performed before starting nefazodone therapy and patients should be monitored regularly. Therapy should be discontinued if liver enzyme concentrations become abnormal.
10.7326/0003-4819-130-4-199902160-00013
pubmed_365_22531
OBJECTIVE In order to avoid sternotomy-related complication after cardiac surgery minimally invasive cardiac surgery has been developed successfully for the treatment of coronary artery disease, however, those techniques were still limited to the treatment of single-vessel disease. Therefore a new surgical technique for the treatment of multi-vessel disease has been developed. METHODS From November 1996 to May 1997 61 patients (age 39-78 years) with coronary artery disease were treated with this new technique. This technique included a small (6-9 cm) left lateral chest incision via the 3rd intercostal space. The left internal thoracic mammary artery (LIMA) was harvested through the chest incision and access to the central portion of the heart including the ascending aorta was obtained. During LIMA harvesting saphenous vein segments were harvested. Cardiopulmonary bypass was instituted through femoral vein cannulation and cannulation of the ascending aorta in most cases. After external aortic cross clamping cold antegrade cardioplegia was applied. In all patients except one the LIMA was used for the left anterior descending artery (LAD). In addition vein grafts were used for revascularisation of the other coronary arteries. RESULTS There were no intraoperative complications and all patients survived the procedure. All patients could be weaned from CPB and the postoperative course was uneventful in most patients. Wound complication occurred in two patients. The median hospital stay was 6 days (median +/- SEM). CONCLUSIONS This new technique combines minimally invasive surgical conditions with the safety standards of routine cardiac surgery. With this approach even extensive coronary artery disease can be treated.
10.1016/s1010-7940(98)00104-3
pubmed_552_6218
For correction of the bilateral cleft lip nasal deformity, a modified bilateral reverse U incision is used in combination with a short, forked flap; by using this combination, satisfactory lengthening of the columella, preserving the natural pout of the lip, can be obtained. We have applied this method to 12 cases undergoing secondary repair of bilateral cleft lip in the past 3 years, and the results of this treatment, along with representative photographs of some of our patients, are presented herein.
10.1016/s1010-5182(05)80200-8
pubmed_159_17740
Abstract  Human induced alterations to rivers and steams have resulted in significant changes to the structure and diversity of riparian and aquatic plant communities. These changes will impact on the dynamics of riverine carbon cycles and food web structure and function. Here we investigate the principal sources of organic carbon supporting local shredder communities across a gradient in different levels of anthropogenic development along riverine reaches, in South Australia. In forested/wooded reaches with minimum to limited development, semi-emergent macrophytes were the principal sources of organic carbon supporting the local shredder communities. However, in developed reaches, course particulate organic matter and filamentous algae were the principal food sources. The C:N ratios of the food sources in developed reaches were higher than those of their consumers indicating a stoichiometric mismatch. This imbalanced consumer-resource nutrient ratio in those developed reaches is likely to impose constraints on the growth and reproduction of their aquatic shredder communities with probable knock-on effects to higher trophic levels.
10.1111/j.1442-9993.2008.01834.x
pubmed_622_1318
Asian Americans (AA) are thought to have the lowest rates of substance use. This study examined substance use prevalence among 494 urban-dwelling Southeast Asians using snowball techniques. Prevalence estimates were age-adjusted proportionate to the U.S. Asian population. Findings show beer and alcohol consumption approximated the national percentage among 25-44 year olds. U.S.-born were about three times likelier to have past month substance use. Foreign-born Vietnamese were likelier than U.S.-born to use all substances except for beer. U.S.- and foreign-born beer consumption rates were similar. Future research is needed to delineate substance use determinants and patterns in foreign and U.S.-born AA sub-groups.
10.1300/J233v06n01_04
pubmed_246_999
To determine the influence of weight reduction on plasma lipoproteins, studies were carried out in 15 nondiabetic patients of varying degrees of obesity and four obese insulin-dependent diabetics. All studies were carried out on a metabolic ward and patients underwent three dietary periods: Period I, 4 to 5 weeks of weight maintenance in the obese state; Period II, caloric restriction to 1000 kcal/day to a weight loss of within 10% of ideal body weight; and Period III, again weight maintenance for 4 to 5 weeks near ideal body weight. Similar results were obtained for both nondiabetics and diabetics. Many patients had mildly elevated plasma triglycerides in Period I; they fell to the normal range in Period II and remained low in Period III. Total cholesterol levels decreased early in Period II, but levels began to rise near the end of caloric restriction, and in Period III, they were similar to Period I. Low density lipoprotein cholesterol levels followed a pattern similar to that of total cholesterol. High density lipoprotein cholesterol was relatively low in Period I (38 +/- 2 mg/dl +/- SEM); throughout weight loss, levels tended to rise, and in Period III, the average high density lipoprotein cholesterol was significantly higher (46 +/- 2 mg/dl).
10.1161/01.atv.3.2.160
pubmed_278_5523
The increase in food production requires reduction of the damage caused by plant pathogens, minimizing the environmental impact of management practices. Soil-borne pathogens are among the most relevant pathogens that affect soybean crop yield. Soybean sudden death syndrome (SDS), caused by several distinct species of Fusarium, produces significant yield losses in the leading soybean-producing countries in North and South America. Current management strategies for SDS are scarce since there are no highly resistant cultivars and only a few fungicide seed treatments are available. Because of this, innovative approaches for SDS management need to be developed. Here, we summarize recently explored strategies based on plant nutrition, biological control, priming of plant defenses, host-induced gene silencing, and the development of new SDS-resistance cultivars using precision breeding techniques. Finally, sustainable management of SDS should also consider cultural control practices with minimal environmental impact. © 2021 Society of Chemical Industry.
10.1002/ps.6458
pubmed_183_15016
Large-scale transitions between alternative states in ecosystems are known as regime shifts. Once described as healthy and dominated by various marine predators, the Black Sea ecosystem by the late 20th century had experienced anthropogenic impacts such as heavy fishing, cultural eutrophication, and invasions by alien species. We studied changes related to these "natural experiments" to reveal the mechanisms of regime shifts. Two major shifts were detected, the first related to a depletion of marine predators and the second to an outburst of the alien comb jelly Mnemiopsis leidyi; both shifts were triggered by intense fishing resulting in system-wide trophic cascades. The complex nature of ecosystem responses to human activities calls for more elaborate approaches than currently provided by traditional environmental and fisheries management. This implies challenging existing practices and implementing explanatory models of ecosystem interactions that can better reconcile conservation and ecosystem management ideals.
10.1073/pnas.0701100104
pubmed_926_20942
PURPOSE To evaluate the refractive predictability and efficacy of Descemet membrane endothelial keratoplasty (DMEK) for patients with previous laser refractive surgery. METHODS We retrospectively reviewed our cohort of endothelial keratoplasty surgical cases. We identified 21 eyes that underwent laser-assisted in situ keratomileusis (n = 17) or photorefractive keratectomy (n = 4) and were treated with DMEK for endothelial failure. Patients were analyzed preoperatively and at 6 months postoperatively for changes in visual acuity, refraction, and corneal topography. RESULTS Six months after surgery, eyes significantly improved to a mean best-corrected visual acuity of 20/23 (P < 0.001). Mean astigmatism amplitude changed from 1.13 ± 0.96 preoperatively to 0.92 ± 0.51 diopters postoperatively (P = 0.28). However, shifts in the axis of corneal astigmatism ranged from 1 to 70 degrees, with 6 eyes (30%) showing an axis shift of more than 30 degrees. Spherical equivalents in nontriple procedures remained unchanged (n = 16; P = 0.69) at 6 months. CONCLUSIONS DMEK and DMEK triple procedures are predictable in patients with previous refractive surgery achieving good visual results. However, refraction after the use of toric intraocular lenses may be unpredictable because of the variability in changes of the magnitude and axis of corneal astigmatism; we recommend extreme caution in the use of the toric intraocular lens in this group of patients and proper counseling for possible individual postoperative residual astigmatism.
10.1097/ICO.0000000000001321
pubmed_897_12528
4'-n-Butoxy-2,4-dimethoxy-chalcone (MBC) has been described as protecting mice from an otherwise lethal infection with Plasmodium yoelii when dosed orally at 50 mg/kg/dose, daily for 5 days. In contrast, we found that oral dosing of MBC at 640 mg/kg/dose, daily for 5 days, failed to extend the survivability of P. berghei-infected mice. The timing of compound administration and metabolic activation likely contribute to the outcome of efficacy testing in vivo. Microsomal digest of MBC yielded 4'-n-butoxy-4-hydroxy-2-methoxy-chalcone and 4'-(1-hydroxy-n-butoxy)-2,4-dimethoxy-chalcone. We propose that the latter will hydrolyze in vivo to 4'-hydroxy-2,4-dimethoxy-chalcone, which has greater efficacy than MBC in our P. berghei-infected mouse model and was detected in plasma following oral dosing of mice with MBC. Pharmacokinetic parameters suggest that poor absorption, distribution, metabolism and excretion properties contribute to the limited in vivo efficacy observed for MBC and its analogs.
10.1159/000322532
pubmed_138_2075
Four neurotoxins that activate the action potential Na+ ionophore of electrically excitable neuroblastoma cells interact with two distinct classes of sites, one specific for the alkaloids veratridine, batrachotoxin, and aconitine, and the second specific for scorpion toxin. Positive heterotropic cooperativity is observed between toxins bound at these two classes of sites. Tetrodotoxin is a noncompetitive inhibitor of activation by each of these toxins (KI = 4-8 nM). These results suggest the existence of three functionally separable components of the action potential Na+ ionophore: two regulatroy components, which bind activating neurotoxins and interact allosterically in controlling the activity of a third ion-transport component, which binds tetrodotoxin.
10.1073/pnas.72.5.1782
pubmed_147_986
Altered plasma neutrophil microparticle levels have recently been implicated in a number of vascular and inflammatory diseases, yet our understanding of their actions is very limited. Herein, we investigate the proteome of neutrophil microparticles in order to shed light on their biological actions. Stimulation of human neutrophils, either in suspension or adherent to an endothelial monolayer, led to the production of microparticles containing >400 distinct proteins with only 223 being shared by the two subsets. For instance, postadherent microparticles were enriched in alpha-2 macroglobulin and ceruloplasmin, whereas microparticles produced by neutrophils in suspension were abundant in heat shock 70 kDa protein 1. Annexin A1 and lactotransferrin were expressed in both microparticle subsets. We next determined relative abundance of these proteins in three types of human microparticle samples: healthy volunteer plasma, plasma of septic patients and skin blister exudates finding that these proteins were differentially expressed on neutrophil microparticles from these samples reflecting in part the expression profiles we found in vitro. Functional assessment of the neutrophil microparticles subsets demonstrated that in response to direct stimulation neutrophil microparticles produced reactive oxygen species and leukotriene B4 as well as locomoted toward a chemotactic gradient. Finally, we investigated the actions of the two neutrophil microparticles subsets described herein on target cell responses. Microarray analysis with human primary endothelial cells incubated with either microparticle subset revealed a discrete modulation of endothelial cell gene expression profile. These findings demonstrate that neutrophil microparticles are heterogenous and can deliver packaged information propagating the activation status of the parent cell, potentially exerting novel and fundamental roles both under homeostatic and disease conditions.
10.1074/mcp.M113.028589
pubmed_445_10892
In the absence of added hemin, protein synthesis in rabbit reticulocyte lysates proceeds at maximal linear rates for several minutes and then ceases abruptly. Inhibition involves the action of a translational inhibitor whose formation is regulated by hemin. Addition of the isolated inhibitor to hemin-supplemented lysates produces an inhibition of protein chain initiation similar to that observed in heme-deficiency. The inhibitor has been purified over 300-fold and contains a protein kinase activity that copurifies with the inhibitory function. With calf thymus histone II as the phosphate receptor, the inhibitor-associated protein kinase requires ATP as the phosphorylating agent. Cycle AMP stimulates kinase activity 5- to 8-fold; the concentration of cycle AMP required for halfmaximal activity is 4 X 10-8 M. Preincubation of the inhibitor in the presence of cyclic AMP significantly reduces cyclic AMP-dependent phosphorylation and inhibitory activity. The corresponding protein kinase activity from hemin-supplemented lysates displays reduced cyclic AMP-dependency and little or no inhibitory activity. These findings suggest that the protein kinase activity associated with the purified translational inhibitor is involved in the mechanism of inhibition of initiation observed in hemedeficient reticulocyte lysates.
10.1073/pnas.72.12.4849
pubmed_32_19617
The effects of continuous in vitro exposure to the trichothecene, vomitoxin (VT) or another protein synthesis inhibitor, cycloheximide (CHX), on interleukin (IL) secretion and mRNA levels were evaluated in murine splenic CD4+ cells. Significant increases were seen in supernatant IL-2, IL-4 and IL-5 obtained from 7 day Concanavalin A (Con A)-stimulated CD4+ cultures containing VT concentrations of 250, 100 and 100 ng/ml, respectively, compared with controls run in the absence of VT. The effect of VT on CD4+ cell proliferation was also assessed after culturing for 3, 5 and 7 days with Con A. Although total cell numbers were not affected at day 3, cultures at day 5 with 50 or more ng VT/ml and at day 7 with 100 or more ng VT/ml had significantly lower cell numbers than controls. In addition, viable cell number was unaffected at day 3, but was significantly decreased at day 5 by VT concentrations of 12.5 ng or more ml and at day 7 by 100 or more ng VT/ml. Elevations in IL-2, IL-4 and IL-5 were also observed in 7-day Con A-stimulated CD4+ cell cultures containing CHX at 50-100, 50 and 10 ng/ml, respectively. When CD4+ cells were stimulated with Con A in the absence of inhibitors and then subjected to reverse transcriptase-polymerase chain reaction coupled with Southern analysis, maximal IL-2, IL-4 and IL-6 mRNA levels were induced at 48 hr whereas peak IL-5 mRNA was observed at 72 hr. Superinduction of IL-2 mRNAs was observed in the presence of VT at 50-100 ng/ml and CHX at 50-250 ng/ml. IL-4 and IL-5 mRNAs were superinduced by VT at 100 ng/ml and CHX at 50 ng/ml. The results suggest that VT and CHX could superinduce both interleukin secretion and mRNA transcript levels in CD4+ cell cultures and that, for VT, these effects occurred concurrently with inhibition of cell proliferation.
10.1016/0278-6915(95)00012-q
pubmed_485_556
Measurement of transcutaneous oxygen pressure (TCPO2) is an established and noninvasive way of assessing cutaneous hypoxia. Since the degree of oxygenation modulates fibroblast growth and synthesis, we investigated the presence of cutaneous hypoxia in patients with systemic sclerosis (SS). We measured TCPO2 of the involved skin of the dorsal aspect of the forearm in 33 patients with SS and 16 control individuals (normal subjects and patients with Raynaud's disease). The degree of forearm skin thickness was assessed clinically as mild, moderate, or severe. The TCPO2 measurements were obtained at a sensor temperature of 44 degrees C, which causes maximal vasodilation and eliminates the variables associated with vascular tone. Measurements were recorded while patients were breathing room air or 31% oxygen delivered by a Ventimask system (Baxter Healthcare, Ocala, Fla). We also measured the TCPO2 of the medial aspect of the arm when this site was uninvolved. We found that sclerodermatous skin is hypoxic when compared with the uninvolved skin of patients with SS or control individuals. The TCPO2 values were indirectly related to skin thickness; thus, patients whose skin was severely thickened had the lowest TCPO2 values. There was no correlation of TCPO2 values with pulmonary function tests or arterial oxygen pressure. The TCPO2 levels of patients with Raynaud's disease did not differ from other control individuals. The administration of oxygen increased TCPO2 readings in patients with SS to normal values. We conclude that the thickened skin of patients with SS is hypoxic and suggest that TCPO2 measurements may be helpful in objectively assessing the degree of skin thickness. The hypoxia demonstrated in SS skin may play a role in the modulation of dermal fibroblast proliferation and synthetic activity.
pubmed_485_556
pubmed_507_17791
Oligo(ethylene glycol) methyl ether methacrylates (OEGMA) of various chain lengths (i.e., 9, 23, or 45 EG units) and N,N-dimethylaminoethyl methacrylate (DMAEMA) were copolymerized by atom transfer radical polymerization (ATRP), yielding well-defined P(DMAEMA-co-OEGMA) copolymers with increasing OEGMA molar fractions (F(OEGMA)) but a comparable degree of polymerization (DP approximately 120). Increase of both F(OEGMA) and OEGMA chain lengths correlated inversely with gene vector size, morphology, and zeta potential. P(DMAEMA-co-OEGMA) copolymers prevented gene vector aggregation at high plasmid DNA (pDNA) concentrations in isotonic solution and did not induce cytotoxicity even at high concentrations. Transfection efficiency of the most efficient P(DMAEMA-co-OEGMA) copolymers was found to be >10-fold lower compared with branched polyethylenimine (PEI) 25 kDa. Although OEGMA copolymerization largely reduced gene vector binding with the cell surface, cellular internalization of the bound complexes was less affected. These observations suggest that inefficient endolysosomal escape limits transfection efficiency of P(DMAEMA-co-OEGMA) copolymer gene vectors. Despite this observation, optimized p(DMAEMA-co-OEGMA) gene vectors remained stable under conditions for in vivo application leading to 7-fold greater gene expression in the lungs compared with PEI. Tailor-made P(DMAEMA-co-OEGMA) copolymers are promising nonviral gene transfer agents that fulfill the requirements for successful in vivo gene delivery.
10.1021/bm9008759
pubmed_565_17019
The measurement of regional cerebral blood flow (rCBF) by single-photon emission computed tomography (SPECT) is a powerful clinical and research tool. There are several clinical applications now documented, a substantial number under active investigation, and a larger number yet to be studied. Standards regarding patient imaging environment and image presentation are becoming established. This article reviews key aspects of SPECT functional brain imaging in clinical practice, with a particular emphasis on therapeutics, including 1) the quality of the tomographic device, 2) the radiopharmaceutical employed, 3) environmental conditions at the time of radiotracer administration, 4) characteristics of the subject, 5) the format used for image presentation, and 6) the essential components of image processing necessary to the achievement of high-quality SPECT brain images. Next, a brief description of relevant radiation safety issues is provided. Finally, applications in molecular imaging, especially in small animal imaging for research as well as drug discovery and development are discussed. The gamut of SPECT studies from currently routine clinical applications to molecular imaging offers a wonderful frontier for opportunities to employ functional brain imaging in neurotherapeutics.
10.1602/neurorx.2.2.237
pubmed_777_5475
Adenosine is a key endogenous molecule that regulates tissue function by activating four G-protein-coupled adenosine receptors: A1, A2A, A2B and A3. Cells of the immune system express these receptors and are responsive to the modulatory effects of adenosine in an inflammatory environment. Animal models of asthma, ischaemia, arthritis, sepsis, inflammatory bowel disease and wound healing have helped to elucidate the regulatory roles of the various adenosine receptors in dictating the development and progression of disease. This recent heightened awareness of the role of adenosine in the control of immune and inflammatory systems has generated excitement regarding the potential use of adenosine-receptor-based therapies in the treatment of infection, autoimmunity, ischaemia and degenerative diseases.
10.1038/nrd2638
pubmed_348_122
Uveitis, or intraocular inflammation, remains an ongoing challenge to ophthalmologists and patients alike. In most patients, uveitis is limited to the anterior ocular structures and is readily managed with topical steroids. The inflammatory process can extend behind the lens to involve the pars plana, the vitreous cavity, the choroid and the retina. These intermediate and posterior uveitides are relatively rare but contribute disproportionately to visual morbidity and present serious diagnostic and therapeutic difficulties. Systemic steroids constitute the first line of treatment for most sight-threatening uveitides. Their long term use is limited by universal and debilitating adverse effects. Second-line, steroid-sparing agents allow a reduction in steroid dosage. Cyclosporin and azathioprine are the main steroid-sparing agents currently in use. However, these compounds are limited by a narrow therapeutic window and significant adverse effects. This paper offers a brief discussion of some of the immune mechanisms involved in the pathogenesis of uveitis and reviews categories of investigational compounds. Inhibitors of T cell function: tacrolimus (previously FK506), licensed for use in liver transplantation, and sirolimus (rapamycin) are macrolide antibiotics. Sirolimus is a functional cytokine antagonist and in vitro studies suggest it could be up to 100 times more potent than cyclosporin. Drug synergy between sirolimus and cyclosporin has been demonstrated, resulting in immunosuppression at lower drug doses and with fewer adverse effects. Nucleotide synthesis inhibitors: mycophenolate mofetil (MMF) and leflunomide. Human lymphocytes are only able to synthesise nucleic acids de novo. Having no alternative or 'salvage' pathway, they are exquisitely sensitive to interference with the de novo nucleotide synthesis enzymatic pathway. MMF is a purine synthesis inhibitor. Compared to other purine inhibitors, early data suggest that MMF is more efficacious and less toxic than azathioprine. Leflunomide is an inhibitor of pyrimidine synthesis. Monoclonal surface receptor antibodies and immunoadhesins: the IL-2 receptor is essential for clonal expansion of activated T cells; this has led to the development of anti-IL-2 receptor antibodies. Daclizumab is a genetically engineered humanised IgG1 monoclonal antibody. In conjunction with cyclosporin, it significantly reduces renal allograft rejection rates and is also showing promise in the treatment of T cell mediated autoimmune disorders. The mechanism of action of monoclonal antibodies to other pro-inflammatory cytokines such as TNFalpha and IL-12 and data from animal and human uveitis trials are also discussed. Finally, new avenues of research in immunopharmaco-modulation are mentioned.
10.2165/00063030-200013060-00003
pubmed_278_22546
In this paper, a novel porous starch with a V-type crystalline structure and high adsorption capacity was obtained by enzymatic hydrolysis of V-type granular starch (VGS) in an aqueous ethanol solution. The effects of different starch concentrations, reaction temperatures, and ethanol concentrations on the microstructure, crystal morphology, crystallinity and adsorption properties of VGS before and after enzymatic hydrolysis were studied, and native normal corn starch (NNCS) and A-type porous starch (APS) prepared by enzymatic hydrolysis of NNCS were used as controls. The results showed that compared with NNCS, VGS was easier to hydrolyze with a higher hydrolysis degree and the corresponding V-type porous starch (VPS) had more and larger pores and thus showed better adsorption performance than APS. Under the same enzymatic hydrolysis time, temperature and rotation speed, VPS prepared with a starch concentration of 20%, reaction temperature of 140 °C and ethanol concentration of 70% showed an irregular spongelike porous structure, highest V-type relative crystallinity of 25.09%, highest oil adsorption capacity of 241.70% and water adsorption capacity of 805.59%.
10.1016/j.ijbiomac.2021.05.006
pubmed_687_3574
The Ochrobactrum genus consists of an extensive repertoire of biotechnologically valuable bacterial strains but also opportunistic pathogens. In our previous study, a novel strain, Ochrobactrum sp. POC9, which enhances biogas production in wastewater treatment plants (WWTPs) was identified and thoroughly characterized. Despite an insightful analysis of that bacterium, its susceptibility to bacteriophages present in WWTPs has not been evaluated. Using raw sewage sample from WWTP and applying the enrichment method, two virulent phages, vB_OspM_OC and vB_OspP_OH, which infect the POC9 strain, were isolated. These are the first virulent phages infecting Ochrobactrum spp. identified so far. Both phages were subjected to thorough functional and genomic analyses, which allowed classification of the vB_OspM_OC virus as a novel jumbo phage, with a genome size of over 227 kb. This phage encodes DNA methyltransferase, which mimics the specificity of cell cycle regulated CcrM methylase, a component of the epigenetic regulatory circuits in Alphaproteobacteria. In this study, an analysis of the overall diversity of Ochrobactrum-specific (pro)phages retrieved from databases and extracted in silico from bacterial genomes was also performed. Complex genome mining allowed us to build similarity networks to compare 281 Ochrobactrum-specific viruses. Analyses of the obtained networks revealed a high diversity of Ochrobactrum phages and their dissimilarity to the viruses infecting other bacteria.
10.3390/ijms21062096
pubmed_152_6353
A variety of electronic DNA array devices and techniques have been developed that allow electric field enhanced hybridization to be carried out under special low-conductance conditions. These devices include both planar microelectronic DNA array/chip devices as well as electronic microtiter plate-like devices. Such "active" electronic devices are able to provide controlled electric (electrophoretic) fields that serve as a driving force to move and concentrate nucleic acid molecules (DNA/RNA) to selected microlocation test-sites on the device. In addition to ionic strength, pH, temperature and other agents, the electric field provides another controllable parameter that can affect and enhance DNA hybridization. With regard to the planar microelectronic array devices, special low-conductance buffers were developed in order to maintain rapid transport of DNA molecules and to facilitate hybridization within the constrained low current and voltage ranges for this type of device. With regard to electronic microtiter plate type devices (which do not have the low current/voltage constraints), the use of mixed buffers (low conductance upper chamber/high conductance lower chamber) can be used in a unique fashion to create favorable hybridization conditions in a microzone within the test site location. Both types of devices allow DNA molecules to be rapidly and selectively hybridized at the array test sites under conditions where the DNA in the bulk solution can remain substantially denatured.
10.1002/1522-2683(200205)23:10<1543::AID-ELPS1543>3.0.CO;2-#
pubmed_716_26064
OBJECTIVES Bibliometric analysis can provide insight into the growth, development and dissemination of research in neurosurgery. Little work has been done to examine the role of country-specific characteristics affecting research productivity. We aimed to characterize andcompare the research productivity among SEA countries in terms of bibliometric indicesand determine associations with country-specific factors. METHODS We performed a systematic search of all articles by authors affiliated with a neurosurgical department in any of the Southeast Asian countries, indexed in 3 databases from inception to June 10, 2020. Bibliometric indices - number of publications, number of citations, average citations per publication, h-index, and the i-10-index - were computed for each country. Correlations between the indices and country-specific characteristics (population size, GDP per capita, percentage of GDP allocation to research and development (R&D), number of neurosurgeons, number of neurosurgeons per capita, and number of collaborations with non-SEA authors) were determined. RESULTS The number of publications showed an increasing trend up to 2019. Most studies were cohort studies (37%) or case reports or series (37%). Of the country-specific factors analyzed, only percentage of the GDP allocated to R&D was positively correlated with number of publications (p = 0.0004), total citations (p < 0.0001), H-index (p < 0.0001), and i(10)-index (p < 0.0001). Number of collaborations also positively correlated with the same indices. CONCLUSION Our bibliometric analysis showed increasing contribution by neurosurgeons in the SEA region. Correlational analysis support the view that increased R&D budget allocation and international collaboration can improve neurosurgical research capacity and productivity.
10.1016/j.jocn.2022.10.028
pubmed_781_16262
BACKGROUND Carriers of plasminogen activator inhibitor -1 (PAI-1) -675 genotype 5G/5G may be associated with lower preoperative PAI-1 plasma levels and higher blood loss after heart surgery using cardiopulmonary bypass (CPB). We speculate if polymorphisms of PAI-1 -844 A/G and angiotensin converting enzyme (ACE) intron 16 I/D also might promote fibrinolysis and increase postoperative bleeding. METHODS We assessed PAI-1 -844 A/G, and ACE intron 16 I/D polymorphisms by polymerase chain reaction technique and direct sequencing of genomic DNA from 83 open heart surgery patients that we have presented earlier. As primary outcome, accumulated chest tube drainage (CTD) at 4 and 24 h were analyzed for association with genetic polymorphisms. As secondary outcome, differences in plasma levels of PAI-1, t-PA/PAI-1 complex and D-dimer were determined for each polymorphism. SPSS® was used for statistical evaluation. RESULTS The lowest preoperative PAI-1 plasma levels were associated with PAI-1 -844 genotype G/G, and higher CTD, as compared with genotype A/A at 4 and 24 h after surgery. Correspondingly, 4 h after the surgery CTD was higher in carriers of ACE intron 16 genotype I/I, as compared with genotype D/D. PAI-1 plasma levels and t-PA/PAI-1 complex reached nadir in carriers of ACE intron 16 genotype I/I, in whom we also noticed the highest D-dimer levels immediately after surgery. Notably, carriers of PAI-1 -844 genotype G/G displayed higher D-dimer levels at 24 h after surgery as compared with those of genotype A/G. CONCLUSIONS Increased postoperative blood loss secondary to enhanced fibrinolysis was associated with carriers of PAI-1 -844 G/G and ACE Intron 16 I/I, suggesting that these genotypes might predict increased postoperative blood loss after cardiac surgery using CPB.
10.1186/s12871-015-0101-1
pubmed_150_3682
Adjuvants have a key role in subunit vaccine formulations to generate protective immune responses. Herein, we present results of a comparative study on mice immunized with E. coli-derived rLmSTI1 antigen formulated with Montanide ISA 720 (Ag-M720) and ISA 50-V2 (Ag-M50) adjuvants against Leishmania major (L. major). Groups of BALB/c mice were immunized with either Ag-M720 or Ag-M50 by 3 subcutaneous injections with 3-week intervals. Three weeks after the last injection mice were challenged by L. major promastigotes. Immune responses were evaluated before, 3 weeks, and 8 weeks after challenge. Results indicated lower parasite and lesion size in vaccinated mice (the lowest for Ag-M720 indicating the best protection) which correlated with higher IFN-γ induction in immunized groups (Ag-M720 and Ag-M50) compared to control (PBS/adjuvant alone) group. Immune assays showed comparable IFN-γ, total IgG, IgG1 and IgG2a levels for Ag-M720 and Ag-M50 immunized mice but higher induction of IL-4, IL-10 and IL-17 in Ag-M50 and the highest IL-10/IL-17 ratio in Ag-M720 group followed by Ag-M50 and control groups. Altogether, results indicated that lower induction of IL-4, IL-10 and IL-17 cytokines (and/or higher ratio of IL-10/IL-17) despite comparable IFN-γ might be the reason for the superior protection in Ag-M720 group.
pubmed_150_3682
pubmed_195_22738
Elliot et al. (2010) reported multiple experimental findings that the color red modified women's ratings of attractiveness, sexual desirability, and status of a photographed man. An analysis of the reported statistics of these studies indicates that the experiments lack sufficient power to support these claims. Given the power of the experiments, the probability that the observed 12 findings would all reject the null hypothesis is only .005. Thus, the proper interpretation of the findings is that the studies are contaminated with publication bias. Either some experiments with null findings were not reported or the reported experiments were run improperly in a way that inflated the likelihood of rejecting the null hypothesis. Because of the presence of publication bias, the findings in Elliot et al. (2010) should be considered nonscientific or anecdotal. It remains an open question whether the color red influences women's ratings of men's attributes.
10.1037/a0027923
pubmed_559_20894
A survey of medicinal plants used by rural population in Bidar district, Karnataka, India is reported. Eighteen plant species belonging to 13 families and 18 genera were included. Their botanical and vernacular names, plant part used, popular medicinal use, forms of preparation and application of the herbal remedies are given.
10.1016/j.fitote.2006.06.017
pubmed_123_11585
We have developed a monoclonal antibody AF-28 that specifically recognizes a neo-epitope on polypeptides with N-terminal FFGVG ... sequences. This sequence is found at the N-terminus of aggrecan fragments that have been digested with matrix metalloproteinases (MMPs). By immunoblotting, monoclonal antibody AF-28 specifically detected G2 fragments derived from an aggrecan G1-G2 substrate digested with stromelysin, collagenase, gelatinase and matrilysin, but failed to detect G2 fragments obtained from elastase, trypsin or cathepsin B digests. Undigested G1-G2 was not detected. In addition, AF-28 antibody detected fragments derived from whole aggrecan and this detection did not require prior treatment with chondroitinase or keratanase. Competition experiments confirmed that peptides containing internal ... FFGVG ... sequences were not detected by the antibody, while native MMP-digested aggrecan fragments and a synthetic 32-mer peptide with FFGVG ... N-termini were equally competitive on a molar basis. An FFGVG 5-mer, and an FGVGGEEDI9-mer which lacked the N-terminal phenylalanine residue, were 50 times and 230 times respectively less competitive than the FFGVG ... 32-mer. Two fragments from the interglobular domain, F342-F373 and F342-D441, that are predicted products of G1-G2 digestion by neutrophil collagenase but have not previously been detected, could be detected with AF-28. The epitope recognized by AF-28 was also detected in human synovial fluids by Western blot analysis. A broad band of 100-200 kDa was detected in some patients and a dominant band of 40-60 kDa was found in two patients. The size of this small fragment corresponds with that seen for the porcine F342-E373 product and may represent the natural physiological product of aggrecan cleaved in vivo at both the MMP site (... DIPEN341 decreases F342FGVG ...) and the aggrecanase site (... ITEGE373 decreases A374RGSVI ...).
10.1042/bj3100337
pubmed_521_3919
The adsorption of beta-lactoglobulin, bovine serum albumin, alpha-lactalbumin, and beta-casein for 8 h and beta-lactoglobulin and bovine serum albumin for 1 h at silanized silica surfaces of low and high hydrophobicity, followed by incubation in buffer and contact with Listeria monocytogenes, resulted in different numbers of cells adhered per unit of surface area. Adhesion to both surfaces was greatest when beta-lactoglobulin was present and was lowest when bovine serum albumin was present. Preadsorption of alpha-lactalbumin and beta-casein showed an intermediate effect on cell adhesion. Adsorption of beta-lactoglobulin for 1 h resulted in a generally lower number of cells adhered compared with the 8-h adsorption time, while the opposite result was observed with respect to bovine serum albumin. The adhesion data were explainable in terms of the relative rates of arrival to the surface and postadsorptive conformational change among the proteins, in addition to the extent of surface coverage in each case.
10.1128/aem.60.10.3560-3565.1994
pubmed_400_7820
BACKGROUND Assistance with exit from endocytic vesicles is a key factor for non-viral gene delivery, and is a particular challenge in vivo. We have evaluated the in vivo use of chloroquine administered systemically, orally and/or locally for gene delivery to the liver. METHODS The DNA vector (polylysine-molossin) is a 31 amino acid bifunctional synthetic peptide, incorporating an amino terminal chain of 16 lysines for electrostatic binding of DNA. Gene delivery was to the right lateral lobes of the liver by branches of the bile duct or portal vein. RESULTS Single intraperitoneal injections of 8, 25 and 75 mg/kg of chloroquine (the maximum tolerated single intraperitoneal dose) resulted in increasing levels of luciferase reporter gene expression, following gene delivery via the bile duct. 100 mg/kg of chloroquine orally was equivalent to 25 mg intraperitoneally. A 3-day course of intraperitoneal and oral chloroquine gave approximately 10-30-fold higher gene expression than an optimal single dose, and resulted in a scattering of positive hepatocytes in the lobule. Gene delivery via the bile duct was much more effective than via the portal vein. Serum chloroquine levels at the time of gene delivery showed a highly significant correlation with gene expression, but the maximum achievable levels in vivo ( approximately 1-2 micro M) were much lower than those required for optimal in vitro gene delivery. Chloroquine (0.2-5 mM) was also given locally in the bile duct with vector/DNA complexes. Maximum gene expression was obtained with 0.5 mM local chloroquine, but the level of gene expression was only equivalent to the 25 mg intraperitoneal dose. CONCLUSIONS The in vivo use of chloroquine is effective for promoting gene delivery to the liver, but requires multiple dosing and is limited by systemic toxicity.
10.1002/jgm.340
pubmed_57_5976
PURPOSE To identify and characterize the presence of body pain related to voice usage in choral singers. METHODS A questionnaire investigating the occurrence of voice problems, vocal self-evaluation, and a report of body aches was given to 50 classical choral singers and 150 participants who were non-singers. Thirteen types of aches were investigated that were distributed into two groups: larynx proximal ache (temporomandibular joint, tongue, sore throat, neck, back of the neck, shoulder, and pain while speaking) and distal ache (headache, backache, chest, arms, hands, and ear ache). RESULTS Classical choral singers had less presence of pain than the general population. The most related pain types reported in singers were sore throat, chest, and shoulder, respectively. CONCLUSION Reduced vocal signs of pain in singers may suggest that singers can benefit from vocal training once they have better voice usage due to voice practice, offering a protective -effect to the development of voice disorders since voice training builds up a better musculoskeletal endurance.
pubmed_57_5976
pubmed_340_18423
In Alzheimer's disease (AD), atrophy negatively impacts cognition while in healthy adults, inverse relationships between brain volume and cognition may occur. We investigated correlations between gray matter volume and cognition in elderly controls, AD and mild cognitive impairment (MCI) patients with memory and executive deficits. AD demonstrated substantial loss in temporal, parietal and frontal regions while MCI exhibited moderate volume loss in temporal and frontal regions. In controls, memory and executive function were negatively correlated with frontal regions, while in AD, memory was positively correlated with temporal and frontal gyri, and executive function with frontal regions. The combination of the two patterns may explain the lack of correlations in MCI. Developmental versus pathological contributions to these relationships are discussed.
10.1016/j.neulet.2006.07.029
pubmed_207_3162
Solvents are extensively used in pesticide formulations. This study concerns the solvents notified to the Italian Registry of Pesticides, which has information on approximately 8000 pesticide formulations. Solvents with evidence of carcinogenicity in humans or animals, including benzene, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,4-dioxane, and 2-nitropropane, have been notified for use in pesticides. Exposure to such solvents could partly explain some of the reported excesses of leukemia and non-Hodgkin's lymphoma among farmers.
10.5271/sjweh.1502
pubmed_443_1828
Full-thickness penile skin grafts have long proved to be valuable in substitution urethroplasty. However, occasional cases of poor graft take, sacculation, or shrinkage of the repairs have mitigated their success. A determining factor in the outcome of grafts is their mechanical support. Historically, ventral placement of the graft has been used, primarily because of the simplicity of access and the excellent graft bed offered by the spongy tissue. However, mechanical support in this location is suboptimal in comparison with that offered by the corpora cavernosa. Recently, dorsal placement of the graft has been proposed, allowing the skin patch to be spread fixed on the tunica albuginea of the corporal bodies overlying the stricture. Fixation of the graft may minimize its retraction and increase its neovascularization. To date, this innovation has proved to be very promising.
10.1007/s003450050049
pubmed_1100_7141
Human thyroglobulin (Tg) was purified from thyroids of normal individuals and of patients with Graves' disease using gel filtration (Sephacryl S-400) and ion-exchange (DEAE) column chromatography. We isolated five protein peaks of Tg from the DEAE column, using a step gradient, characterized them for protein and iodine content, and assessed their immunological properties by reactivity to polyclonal and monoclonal antibodies (mAbs). Normal and Graves' Tgs differed in the relative protein content of these five protein peaks from the DEAE column. In the case of normal Tg, the majority of Tg was eluted in peak 2 but in the Graves' Tg, most of the protein was eluted in peak 1 of this column. The immunoreactivity of these five protein peaks of Tg was studied using 11 mouse mAbs prepared against human Tg, sera from patients with autoimmune thyroiditis and polyclonal antibody from a rabbit immunized with human Tg. All of five protein peaks of Tg reacted equally with rabbit antibody. The sera of five thyroiditis patients showed greater binding to peak 1 of Graves' Tg than peak 1 of normal Tg. Similarly, most mAbs showed greater binding to peak 1 of Graves' Tg than the peak 1 of normal Tg. Of particular interest was one mAb (42C3) which reacted only with Tgs containing iodine. The immunoreactivity of this mAb paralleled the iodine content of Tg. This mAb might be useful for evaluating the role of iodine in the antigenicity of human Tg.
10.1006/clin.1994.1115
pubmed_337_6549
A simple mixed-micelle mediated extraction was elaborated for the preconcentration and determination of scandium(III) by inductively coupled plasma optical emission spectrometry. Scandium(III) was complexed with Alizarin Red S and cetyltrimethylammonium bromide at pH 3 to form hydrophobic chelates, which could be extracted with Triton X-114 at room temperature (25°C) in the presence of KI as a salting-out electrolyte. The main parameters of the extraction procedure were investigated in regard to the extraction efficiency of scandium(III). Under the optimum conditions, a linear range of 0.5 - 150 ng mL(-1) and a detection limit of 0.2 ng mL(-1), along with a preconcentration factor of 100, were achieved. Furthermore, the interference of diverse ions accompanying scandium(III) was extensively studied. The obtained results indicate the high selectivity of the proposed procedure. The accuracy of the procedure was verified through recovery experiments on spiked water samples and synthetic mixtures. The procedure was successfully applied to a scandium(III) determination in clay samples.
10.2116/analsci.32.395
pubmed_494_18715
PURPOSE KRAS mutations are found in approximately 25% of lung adenocarcinomas in Western countries and, as a group, have been strongly associated with cigarette smoking. These mutations are predictive of poor prognosis in resected disease as well as resistance to treatment with erlotinib or gefitinib. EXPERIMENTAL DESIGN We determined the frequency and type of KRAS codon 12 and 13 mutations and characterized their association with cigarette smoking history in patients with lung adenocarcinomas. RESULTS KRAS mutational analysis was done on 482 lung adenocarcinomas, 81 (17%) of which were obtained from patients who had never smoked cigarettes. KRAS mutations were found in 15% (12 of 81; 95% confidence intervals, 8-24%) of tumors from never smokers. Similarly, 22% (69 of 316; 95% confidence intervals, 17-27%) of tumors from former smokers, and 25% (21 of 85; 95% confidence intervals, 16-35%) of tumors from current smokers had KRAS mutations. The frequency of KRAS mutation was not associated with age, gender, or smoking history. The number of pack years of cigarette smoking did not predict an increased likelihood of KRAS mutations. Never smokers were significantly more likely than former or current smokers to have a transition mutation (G-->A) rather than the transversion mutations known to be smoking-related (G-->T or G-->C; P < 0.0001). CONCLUSIONS Based on our data, KRAS mutations are not rare among never smokers with lung adenocarcinoma and such patients have a distinct KRAS mutation profile. The etiologic and biological heterogeneity of KRAS mutant lung adenocarcinomas is worthy of further study.
10.1158/1078-0432.CCR-08-0646
pubmed_370_4989
Two patients developed severe zinc deficiency with acrodermatitis during parenteral hyperalimentation. The response of circulating T-lymphocytes to phytohemagglutinin was assessed both during the episode of clinical zinc deficiency and after intravenous zinc supplementation as the sole means of nutritional intervention. Maximum T-cell response to phytohemagglutinin, expressed as percent of simultaneous normal control response, was 2.1% and 27.9% in Patients 1 and 2 respectively. After 20 days of intravenous zinc supplementation (12 mg/d), repeat studies showed the T-cell response of Patient 1 to be 221% of the control, and that of Patient 2 to be 139% of control. In addition, Patient 1 was anergic during the period of zinc deficiency and normally reactive after zinc supplementation. These findings agree with extensive animal studies showing the detrimental effect of zinc deficiency on cellular immunity.
10.7326/0003-4819-95-2-154
pubmed_1142_15126
OBJECTIVES The prevalence of depression and insomnia in the military are substantial. Several transcranial magnetic stimulation (TMS) studies have used self-report sleep data as secondary research outcomes; however, there are limited studies using the gold standard of polysomnography (PSG) to ascertain actual sleep changes. Here, we provide data from a pilot and feasibility study using PSG to measure sleep changes after repetitive TMS. METHODS Thirty-eight active duty service members (ADSM) were consented, of which 20 completed the study. The ADSM who met study criteria where sent for an initial PSG and completed baseline self-report measures. They then completed a standard course of TMS, and self-report measures were completed every fifth session. After TMS completion, ADSM underwent final PSG. RESULTS Comparison of baseline and postintervention PSG sleep parameters highlight that total rapid eye movement sleep improved after a course of TMS, regardless of improvements in depression. Total sleep time also improved, but only in the TMS responders subgroup. The Public Health Questionnaire-9 showed statistically significant improvement as did the Insomnia Severity Index and some components of the RAND Medical Outcomes Short Form 36. CONCLUSION Our small study confirms the feasibility of obtaining pre and post PSG for research purposes. We found similar results to previous studies with regard to depression improvement and self-reported sleep. Interestingly, almost all (including electroconvulsive therapy) somatic depression treatments have been shown to decrease REM, whereas our study found an increase in REM. Overall, this study helps further our understanding of TMS effects on sleep and presents new questions for potential larger follow-on studies.
10.1097/YCT.0000000000000767
pubmed_28_26190
The human gastrointestinal tract is in constant contact with microbial stimuli. Its barriers have to ensure co-existence with the commensal bacteria, while enabling surveillance of intruding pathogens. At the centre of the interaction lies the epithelial layer, which marks the boundaries of the body. It is equipped with a multitude of different innate immune sensors, such as Toll-like receptors, to mount inflammatory responses to microbes. Dysfunction of this intricate system results in inflammation-associated pathologies, such as inflammatory bowel disease. However, the complexity of the cellular interactions, their molecular basis and their development remains poorly understood. In recent years, stem cell-derived organoids have gained increasing attention as promising models for both development and a broad range of pathologies, including infectious diseases. In addition, organoids enable the study of epithelial innate immunity in vitro. In this review, we focus on the gastrointestinal epithelial barrier and its regional organization to discuss innate immune sensing and development.
10.1007/s00109-021-02043-9
pubmed_596_4495
Essential tremor (ET) is one of the most common neurological disorders among adults. For many years, ET was viewed as a benign monosymptomatic condition, characterized by a kinetic arm tremor, yet over the last 10 years, a growing body of evidence suggests that this disorder is a progressive condition that is heterogeneous. Tremor may have a negative impact on health-related quality of life in some patients. Pharmacotherapy is initiated when the tremor interferes with the patient's ability to perform daily activities or when the tremor becomes embarrassing or affects health-related quality of life. For severe tremor, deep-brain stimulation of the thalamus may improve function.
10.1016/B978-0-444-52014-2.00034-3
pubmed_541_22793
More than half of all elderly people have some degree of cerebral white matter lesions. However, the rate of progression of these lesions is uncertain. We aimed to assess the progression of lesions in community-dwelling volunteers aged 50-75 years without neuropsychiatric disease. We used MRI to grade and measure the total volume of white matter lesions in 296 volunteers at baseline, 3 years, and 6 years. 58 participants with no lesions and 123 with punctate abnormalities at baseline had a low tendency for lesion progression, whereas 14 participants with early confluent and nine with confluent lesions underwent median increases of 2.7 cm(3) (IQR 0.5-5.9) and 9.3 cm(3) (7.1-21.0), respectively, in lesion volume at 6 years. Lesion grade at baseline was the only significant predictor of lesion progression (p<0.0001). Punctate white matter lesions are not progressive and are thus benign, whereas early confluent and confluent white matter abnormalities are progressive, and thus malignant.
10.1016/s0140-6736(03)13616-1
pubmed_841_3578
The majority of patients with lung cancer have incurable disease from presentation and a survival measured in months. Treatments offered to these patients are aimed at the palliation of symptoms with either radiotherapy or chemotherapy, or with supportive measures. It has been traditional to offer regular outpatient follow-up after initial palliative treatment. Further treatment options, which may be limited, are usually reserved for the recurrence of troublesome symptoms. A pilot 'open access' lung cancer clinic has been set up. Rather than have regular follow-up at the hospital, patients who have completed initial palliative treatments are discharged to the community with follow-up by their general practitioner and Macmillan nurse. Review at the open access clinic can be arranged at short notice if requested by the patient, carers, general practitioner or Macmillan nurse. The outcomes and level of satisfaction of patients, their relatives and staff to this method of follow-up were found to be positive. Open access follow-up may be useful for many patients after the completion of initial palliative treatment.
10.1053/clon.2001.9302
pubmed_270_8842
The aim of the study was to assess neurologic complications of pertussis infection. A file review of all children (age 7-18 years) in our hospital with serology-positive pertussis infection admitted from 1995 to 2005 yielded six patients with neurologic symptoms in whom electroencephalographic studies were performed. Data were collected on their clinical symptoms, electroencephalographic findings, final diagnosis, and outcome. The six patients accounted for 10% of all children diagnosed with pertussis during the study period. Their ages ranged from 10 to 15.5 years. All the children were referred by their primary physician because of a suspicion of epilepsy on the basis of parental reports of inefficient attempts to breathe during sleep accompanied by high-pitched sounds and sounds of suffocation, and sleepwalking. The children were amnesic for the episodes. However, findings on electroencephalogram taken during sleep were negative in all cases. The final diagnosis was partial arousal parasomnia. The symptoms of parasomnia disappeared with resolution of the symptoms of the pertussis infection. In conclusion, partial arousal parasomnia may be induced by pertussis infection. Further studies in larger groups are required to confirm this association.
10.1016/j.pediatrneurol.2006.05.001
pubmed_1053_11980
Aged men, known to have high serum gonadotropin levels and reduced spermatogenic potential, were used to study the relationship between serum follicle-stimulating hormone (FSH) and germ cell degeneration. Serum hormones were measured from blood obtained at autopsy. Phase-contrast cytometry was used to enumerate germ cells in homogenates of fixed testes from 13 younger (24-51 yr) and 14 aged (69-90 yr) men. The developmental steps of spermatogenesis during which germ cells degenerate were determined by comparing potential daily sperm production based on primary spermatocytes with daily sperm production based on two different types of spermatids. During spermiogenesis, there was no significant degeneration in the younger or aged men. During postprophase of meiosis, aged men had more (p less than 0.01) germ cell degeneration, significantly lower (p less than 0.05) serum testosterone, and greater (p less than 0.01) serum FSH than did younger men. Germ cell degeneration during postprophase of meiosis was negatively correlated (p less than 0.01) to daily sperm production and significantly (p less than 0.01) related to serum concentrations of FSH. As revealed in these aged men, meiotic germ cell degeneration has a direct effect on daily sperm production and is significantly related to serum FSH concentrations.
10.1095/biolreprod42.2.281
pubmed_686_9302
OBJECTIVE To determine the clinical characteristics, outcome following surgical treatment, and natural history of cases of untreated vulvar intraepithelial neoplasia (VIN). METHODS Four hundred five cases of VIN 2-3 seen between 1962 and 2003 were reviewed. RESULTS The mean age of women with VIN decreased from 50.0 years before 1980 to 39.0 in subsequent years. After treatment of VIN by excision and/or laser vaporization, half the women required at least one further treatment by the 14th year. It is estimated that 50% of women with positive surgical margins had at least one further treatment within 5 years, but only 15% of women with negative surgical margins required further treatment. Invasive vulvar, perianal, or urethral carcinoma occurred in 17 (3.8%) women (mean age 42 years) after treatment. Nine (2%) cases represented treatment failure, with a median treatment-to-invasion interval of 2.4 years. Eight (1.8%) cases represented new "field" carcinomas, with a median initial treatment-to-invasion interval of 13.5 years. Ten untreated cases, aged 32-76 years (mean age 55 years), progressed to invasion in 1.1-7.3 years (mean 3.9 years). Age, previous pelvic radiotherapy, unifocality, immunosuppression, and association with multicentric neoplasia were not risk factors for the development of invasive vulvar carcinoma in this study. Spontaneous regression of VIN occurred in 47 women (mean age 24.6 years), with a median interval to complete regression of 9.5 months. CONCLUSION Surgically treated VIN has a high rate of recurrence. Untreated VIN in women over 30 years has an appreciable invasive potential.
10.1097/01.AOG.0000187301.76283.7f
pubmed_407_605
Preventive and/or manipulative practices will be needed to maintain soil's biological, physiochemical, nutritional, and structural health in natural, managed, and disturbed ecosystems as a foundation for food security and global ecosystem sustainability. While there is a substantial body of interdisciplinary science on understanding function and structure of soil ecosystems, key gaps must be bridged in assessing integrated agro-biological, ecological, economical, and environmental efficiency of soil manipulation practices in time and space across ecosystems. This presentation discusses the application of a fertilizer use efficiency (FUE) model for assessing agronomic, economic, ecological, environmental, and nematode (pest) management efficiency of soil amendments. FUE is defined as increase in host productivity and/or decrease in plant-parasitic nematode population density in response to a given fertilizer treatment. Using the effects of nutrient amendment on Heterodera glycines population density and normalized difference vegetative index (indicator of physiological activities) of a soybean cultivar 'CX 252', how the FUE model recognizes variable responses and separates nutrient deficiency and toxicity from nematode parasitism as well as suitability of treatments designed to achieve desired biological and physiochemical soil health conditions is demonstrated. As part of bridging gaps between agricultural and ecological approaches to integrated understanding and management of soil health, modifications of the FUE model for analyzing the relationships amongst nematode community structure, soil parameters (eg. pH, nutrients, %OM), and plant response to soil amendment is discussed.
pubmed_407_605
pubmed_205_18872
BACKGROUND Electric conversion of atrial fibrillation is the most widely used and effective treatment for sinus rhythm restoration. However, it has a limited success rate and a high recurrence rate. HYPOTHESIS Pretreatment with calcium channel blocker may improve the efficacy by reversing the so-called "electric remodeling" phenomenon, also related to overload in cytosolic calcium. METHODS The efficacy of diltiazem or amiodarone pretreatment (oral, 1 month before and 1 month after conversion) on direct-current conversion of persistent atrial fibrillation was assessed in 120 patients, randomly assigned to 3 matched groups: A (n = 44, diltiazem); B (n = 46, amiodarone), and C (n = 30, digoxin). RESULTS Before electric conversion, all treatments significantly decreased mean heart rate. Spontaneous conversion to sinus rhythm was achieved in 6% of patients of group A (3 of 46) versus 25% of group B (11 of 44) and 3% (1 of 30) of group C (A/C vs B, P < .005). Current conversion was more successful in group B (91%) compared with group A (76%) and group C (67%) (B vs A/C, P < .05), with no difference in the electric threshold for effective conversion (P = not significant). At the 24-hour time point, early relapse of atrial fibrillation was similar between groups A and B (A, 2%; B, 3%; P = not significant) and lower than group C (12%) (P < .01), whereas at the 1-month time point the recurrence rate was lower in group B (28%) versus groups A (56%) and C (78%) (B vs A/C, P < .01). No significant side effects were reported. CONCLUSIONS Although diltiazem seems to be as effective as amiodarone in reducing early atrial fibrillation recurrences, diltiazem is less effective in determining spontaneous or electric conversion, with a higher recurrence rate at 2 months. Diltiazem pretreatment could be considered as only a second choice treatment in those patients in whom amiodarone is contraindicated.
10.1067/mhj.2000.107179
pubmed_443_4737
The efficacy of submucosal injection of a small dose cyclophosphane for gastric ulcer disease treatment in 88 patients was studied. The significant reduction of ulcer healing time in comparison with such in a control group was noted.
pubmed_443_4737
pubmed_699_18467
INTRODUCTION Sarcopenic obesity (SO) represents the confluence of two epidemics-an aging population and an increasing rate of obesity. The two diseases may act synergistically, and SO may significantly affect morbidity and mortality. However, the burden is not defined to drive the policy changes. Hence the present study was done to estimate the prevalence and predictors of SO in India. METHODS We did a secondary data analysis of the 72,250 older adults who participated in the first wave of the Longitudinal Aging Study in India (2017-18). Possible sarcopenia was defined as per the guidelines by the Asian Working Group for Sarcopenia (AWGS) criteria. The modified criterion of overweight and obesity for Asian adults was used to categorize obesity. Presence of both sarcopenia and obesity depicted SO. Weighted analysis was done to estimate the prevalence of SO, and multinomial bivariate logistics regression was used to identify the predictors of SO. RESULTS The overall prevalence of obesity, sarcopenia, and SO was 27.1%, 41.9%, and 8.7%, respectively. The mean age, weight, body mass index (BMI), and blood pressure of adults with SO were significantly higher compared to others. Higher age, urban residence, west and south regions of India, consumption of tobacco or alcohol, no physical activity, and presence of diabetes contribute to SO. CONCLUSION The burden of SO seems to be less but amounts to a massive number in an aging country. We stress increased screening of the geriatric age group and advocate increased physical activity and dietary modifications to realize the concept of healthy aging.
10.1007/s12325-022-02216-z
pubmed_407_9737
Ureteral stenting is a common practice in human medicine and has recently been reported in dogs and cats to provide urinary diversion for ureteral obstructions caused by ureteroliths, strictures, neoplasia, and in an attempt to prevent postoperative complications following ureteral anastomosis. The aim of this report is to describe a surgical technique of ureteral stenting and the follow-up and complications in nine cats. Number 3 French double-J catheters were used during open surgery for ureterotomy/ureterolith removal in eight cats and for segmental ureterectomy/end-to-end anastomosis in one cat for a localized benign stricture. Neoureterocystostomy was necessary in eight of the cats. Uroperitoneum did not occur. Stents were still in place in 7/9 animals after 357-1,565 days (median 1,277 days). A minor complication (stent migration) occurred in one cat, but stent removal was not required. Major complications were encrustation and persistent stranguria (in one cat each), requiring stent removal at 90 and 123 days, respectively. The first cat had a new stent inserted but was euthanased 3 months later for progressive renal failure. Despite the small number of cats, both the outcome and long-term stent tolerance observed in most cases suggest that ureteral stenting is a safe, adjunctive measure to ureteral surgery, mainly for concomitant ureteral and renal pelvic stones to prevent further obstruction and avoid pyelotomy/nephrotomy. However, smaller stents should be used to decrease the need for ureteral surgery.
pubmed_407_9737
pubmed_2_1572
While TOFA (acetyl CoA carboxylase inhibitor) and C75 (fatty acid synthase inhibitor) prevent lipid accumulation by inhibiting fatty acid synthesis, the mechanism of action is not simply accounted for by inhibition of the enzymes alone. Liver fatty acid binding protein (L-FABP), a mediator of long chain fatty acid signaling to peroxisome proliferator-activated receptor- α (PPAR α ) in the nucleus, was found to bind TOFA and its activated CoA thioester, TOFyl-CoA, with high affinity while binding C75 and C75-CoA with lower affinity. Binding of TOFA and C75-CoA significantly altered L-FABP secondary structure. High (20 mM) but not physiological (6 mM) glucose conferred on both TOFA and C75 the ability to induce PPAR α transcription of the fatty acid β -oxidative enzymes CPT1A, CPT2, and ACOX1 in cultured primary hepatocytes from wild-type (WT) mice. However, L-FABP gene ablation abolished the effects of TOFA and C75 in the context of high glucose. These effects were not associated with an increased cellular level of unesterified fatty acids but rather by increased intracellular glucose. These findings suggested that L-FABP may function as an intracellular fatty acid synthesis inhibitor binding protein facilitating TOFA and C75-mediated induction of PPAR α in the context of high glucose at levels similar to those in uncontrolled diabetes.
10.1155/2013/865604
pubmed_743_16923
BACKGROUND/OBJECTIVES While pain is the predominant symptom of chronic pancreatitis (CP), a subset of patients may experience a painless course. This systematic review aimed to determine the prevalence of primary painless CP. METHODS MEDLINE (PubMed), EMBASE and Web of Science Core Collection databases were searched for published studies through September 15, 2020 that included at least 10 consecutive patients with CP and which reported the number with painless CP. The presence of a history of recurrent acute pancreatitis (RAP), exocrine pancreatic insufficiency (EPI), diabetes mellitus (DM) and pancreatic adenocarcinoma (PA) in the painless CP patients was also recorded. A random effects model was used to determine pooled prevalence estimates with 95% confidence intervals (95% CI). RESULTS Among the 5057 studies identified and screened, 42 full-text articles were included in the final analysis. There were a total of 14,277 patients with CP among whom 1569 had painless CP. The pooled prevalence of painless CP was 12% (95% CI 10-15%). Among a subset of studies that reported on calcifications (n = 11), DM (n = 12), EPI (n = 8) and history of RAP (n = 14), the pooled prevalence estimates were 96% (95% CI 73-100%), 51% (95% CI 32-70%), and 47% (95% CI 15-81%), respectively. Alcohol, idiopathic/genetic and other etiologies were attributed to be the cause of painless CP in 32.4%, 56.9% and 8.9% patients, respectively. CONCLUSION Approximately one in ten patients with CP have primary painless disease with the majority being attributable to an idiopathic/genetic etiology. Further research is needed to determine the optimal management of these patients.
10.1016/j.pan.2021.11.006
pubmed_877_6771
OBJECTIVES To describe the critical need for pharmacists' involvement in outpatient care for people living with cystic fibrosis (CF). DATA SOURCES Not applicable. SUMMARY CF is a pulmonary condition that affects more than 30,000 children and adults in the United States and 70,000 people worldwide. Various complex medication regimens are given to patients with CF, some depending on the type of mutation they have in their CF transmembrane conductance regulator protein. With complex medication regimens and the increased number and variety of treatments that have become available, the medication use burden intensifies for individuals living with CF and their caregivers. Young people living with CF have a particularly difficult time adhering to medications and other therapies as they begin to rely less on their caregivers and assume greater medication management responsibility for their care. Adolescents report low adherence rates from about 40% to 47% for airway clearance methods and even lower for nutritional recommendations, about 16% to 20%. In inpatient settings, pharmacists have been successful in making medication use recommendations that have improved adherence for patients with CF while in the hospital. However, limited research has explored how provision of pharmacist supportive care and patient education in outpatient settings can improve medication adherence and quality of life for people living with CF. CONCLUSION There is potential for provision of outpatient pharmacy clinical services to increase medication adherence and overall quality of care for patients with CF. Higher rates of medication adherence in patients with CF could in turn improve patient outcomes and reduce overall health care costs as a result of fewer rehospitalizations. Pharmacies can implement programs designed to provide comprehensive support services and medication management from pharmacists and staff that are trained in CF care.
10.1016/j.japh.2018.01.006
pubmed_1124_14819
BACKGROUND Factitious disease involving the breast is unusual. The rarely reported cases of this entity have been encountered in middle-aged women. In general, factitious disease can be distinguished on clinical and/or psychological grounds from self-induced disorders seen in malingerers and among those demonstrating Munchausen's syndrome. METHODS We report herein a male patient displaying factitious disease of the breast due to injection of a high viscosity liquid plastic material. RESULTS Establishment of the proper diagnosis was greatly delayed due to a lack of suspicion of this entity. Only direct confrontation of the patient with the biopsy results (lipogranulomatosis) led to a reluctant and then only partial admission of the self-induced nature of this patient's illness. CONCLUSION The clinician should remain vigilant for factitious disease when confronted with chronic or recurrent lesions of a bizarre or atypical morphology. Any body site can be involved, including the breast. Management is difficult and is best accomplished in conjunction with an appropriate mental health professional. Continued dramatic surgical interventions are contraindicated.
10.1046/j.1365-4362.2001.01342.x
pubmed_327_21838
Metabotropic glutamate receptors (mGlu receptors) are coupled to G-protein second messenger pathways and modulate glutamate neurotransmission in the brain, where they are targeted to specific synaptic locations. Very recently, we identified tubulin as an interacting partner of the mGlu(1alpha) receptor in rat brain. Using BHK-570 cells permanently expressing the receptor we have shown that this interaction occurs predominantly with soluble tubulin, following its translocation to the plasma membrane. In addition, treatment of the cells with the agonist quisqualic acid induce tubulin depolymerization and its translocation to the plasma membrane. Immunofluorescence detection of both the receptor and tubulin in agonist-treated cells reveals a disruption of the microtubule network and an increased clustering of the receptor. Collectively these data demonstrate that the mGlu(1alpha) receptor interacts with soluble tubulin and that this association can take place at the plasma membrane.
10.1046/j.1471-4159.2001.00099.x
pubmed_564_18647
The 118 horses diagnosed as suffering from navicular disease by prospective criteria were treated by desmotomy of the ligamenta sesamoidea collateralia (navicular suspensory desmotomy). Three techniques were used and a standard post-operative programme was followed with clinical and radiological evaluations at 6-monthly intervals for periods of 6-36 months after surgery. At 6 and 36 months after treatment, 76% and 42.9% of horses were sound respectively. The clinical features of age, period of lameness, severity of lameness and angular limb deformities adversely affected response to surgery. The presence of flexor cortex defects, proximal border enthesophytes, mineralisation of the flexor digitorum profundus tendon and medullary sclerosis were also associated with a diminished response. There were few (1.7%) changes in the radiological appearance of distal border synovial invaginations during the follow-up period. By contrast, the majority (67.3%) of flexor cortex defects changed. Other radiological features changed at a low frequency but there was no association between radiological change and clinical outcome.
10.1111/j.2042-3306.1993.tb03001.x
pubmed_635_17026
Neuregulin receptor degradation protein-1 (Nrdp1), a kind of ring finger E3 ubiquitin ligase, is expressed in several adult tissues, including the heart, testis, prostate and brain. Studies of this molecule have demonstrated its great importance in regulating cell growth, apoptosis and oxidative stress in various cell types. However, information regarding its expression and possible function in the central nervous system is still limited. In this study, we performed a neuroinflammation model by lipopolysaccharide (LPS) lateral ventral injection in adult rats. It was found that the expression of Nrdp1 was significantly increased in cerebral cortex after LPS injection. Immunofluorescence indicated that Nrdp1 was located in the neurons, but not astrocytes or microglia. Furthermore, there was a concomitant up-regulation of active caspase-3 and decreased expression of BRUCE (an inhibitor of apoptosis protein). In addition, decreasing Nrdp1 levels by RNA interference in cortical primary neurons reduced active caspase-3 expression but induced up-regulation of BRUCE. Collectively, all these results suggested that Nrdp1 might play a role in neuronal apoptosis by reducing the expression of BRUCE in neuroinflammation after LPS injection.
10.1007/s11064-015-1552-y
pubmed_852_13169
Statistical principles are used in nutrition research to plan and conduct research studies and to answer research questions. This article describes general statistical concepts and provides some guidelines to assist in the interpretation of research literature. Prospective and retrospective study designs used in nutrition research are presented as well as the advantages and disadvantages of each of the study designs. Descriptive statistics used to summarize data and graphical tools used to display the shape of the distribution of a set of data guide nutrition support professionals to select appropriate statistical tests. Fundamental topics of statistics, including power analysis and sample size, confidence intervals and hypothesis testing, and analysis of variance and regression, are also reviewed. The article emphasizes the importance of effective collaboration with statisticians at an early stage of the research study to avoid potential pitfalls associated with improper utilization of statistical methods.
10.1177/0884533613478636
pubmed_142_10626
On February 21, 2012, the San Antonio Metropolitan Health District (SAMHD) Tuberculosis Clinic was notified that two students at Madison High School had laboratory-confirmed pulmonary tuberculosis (TB). During March-September 2012, public health officials from SAMHD collaborated with the school district to conduct an outbreak investigation that included performing tuberculin skin tests (TSTs) on high-risk contacts of active TB patients. To ensure compliance, all TSTs were performed at the school. Initial screening was conducted as soon as a contact was identified and was followed by a second TST ≥8 weeks after the patients with active TB were removed from the school. All positive TSTs were confirmed with an interferon gamma release assay (IGRA) (T-Spot.TB, Oxford Immunotec, Inc.) performed by SAMHD laboratory services. IGRA tests can provide additional evidence of infection to encourage acceptance and adherence of foreign-born patients who believe their positive TST is attributable to Bacille Calmette-Guerin vaccination and might also prompt greater acceptance of treatment for latent TB infection compared with a positive TST alone.
10.15585/mmwr.mm6431a5
pubmed_1138_12566
Immediate post-training intraperitoneal administration of alpha-D[+]-glucose (10-300 mg/kg) significantly enhanced retention of male Swiss mice tested 24 h after training in an inhibitory avoidance task. The dose-response curve was an inverted U in this range of dose. However, of the doses tested, only 30 mg/kg was effective. Glucose did not affect response latencies in mice not given the footshock on the training trial, suggesting that the actions of glucose on retention performance were not due to nonspecific effects on response latencies. The influence of glucose (30 mg/kg) was time-dependent, which suggests that glucose facilitated memory consolidation processes. Administration of glucose (30 mg/kg) 2 or 10 min prior to the retention test did not affect the retention performance of mice given post-training injections of either saline or glucose (30 mg/kg). These findings indicate that the memory-enhancing effects of post-training administration of glucose are not state-dependent and are consistent with the view that the behavioral effects of glucose are mediated through an interaction with the neural or neurohumoral processes underlying the storage of acquired information.
10.1016/0163-1047(93)90333-d
pubmed_231_420
Kronish, Donald P. (Warner-Lambert Research Institute, Morris Plains, N.J.), Raam R. Mohan, and Benjamin S. Schwartz. Distribution of radioactivity in autolyzed cell wall of Bacillus cereus during spheroplast formation. J. Bacteriol. 87:581-587. 1964.-Spheroplasts of Bacillus cereus strain T were produced from cells grown in the presence of uniformly labeled C(14)-glucose. At regular intervals during spheroplast formation, enzymatically degraded cell wall was isolated by a new procedure. Radioactivity of solubilized cell wall in cell-free material increased from 2.5 to 42% of the total incorporated label during spheroplast formation. The rate of cell-wall degradation as measured by increase in radioactivity was biphasic with relative slopes of 2.0 and 5.0. During autolytic depolymerization of B. cereus cell wall, two major components were solubilized at different rates. Chemical fractionation revealed these to be a peptide and a mucopeptide. The possibility of two enzymes being involved in spheroplast formation and cell-wall degradation is discussed.
10.1128/jb.87.3.581-587.1964