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pubmed_950_15829
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Alkalization modifies the color and flavor of the cocoa products. The aim of the present survey was to determine how different types and dosage of alkaline relate to the color quality, total polyphenol amount and alkylpyrazine content of cocoa powder. Cameroon cacao beans were used to produce cocoa nibs. The nibs were alkalized with the solutions of NaOH, K2CO3, and NH4HCO3 at their different concentrations and combinations. The browning index (OD460/OD525) and alkylpyrazine content were changed significantly (p ≤ 0.01) with changing the type and the concentration of the alkali solution. The browning index, moisture, ash, and acid-insoluble ash content increased as the concentration of the alkali increased. In general, the not-alkaline products had more polyphenol and ratio of tetramethylpyrazine to trimethylpyrazine than the alkalized ones. Besides, the polyphenol and alkylpyrazine amounts decreased as the concentration of the alkali increased (p ≤ 0.01). At the same concentration, alkalization with a NaOH solution produced a higher polyphenol and alkylpyrazine content, but lower OD460/OD525 value than that with a K2CO3 solution. The samples with a high concentration of alkaline solution had the lowest ratio of monomer anthocyanins to yellow and brown polymers content (F1/F3) value.
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10.1007/s13197-020-04293-w
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pubmed_957_13097
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The aim of this work was to compare the lipidome and metabolome profiling in the Longissimus thoracis muscle early and late postmortem from high and normal ultimate pH (pHu) beef. Lipid profiling discriminated between high and normal pHu beef based on fatty acid metabolism and mitochondrial beta-oxidation of long chain saturated fatty acids at 30 min postmortem, and phospholipid biosynthesis at 44 h postmortem. Metabolite profiling also discriminated between high and normal pHu beef, mainly through glutathione, purine, arginine and proline, and glycine, serine and threonine metabolisms at 30 min postmortem, and glycolysis, TCA cycle, glutathione, tyrosine, and pyruvate metabolisms at 44 h postmortem. Lipid and metabolite profiles showed reduced glycolysis and increased use of alternative energy metabolic processes that were central to differentiating high and normal pHu beef. Phospholipid biosynthesis modification suggested high pHu beef experienced greater oxidative stress.
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10.1016/j.meatsci.2022.108978
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pubmed_647_19716
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A technique for the surgical relocation of the carotid artery, to permit repeated percutaneous puncture, in red deer, is described. An incision was made through the skin distal to the ramus of the jaw parallel to and dorsal to the superficial jugular vein. The brachiocephalicus muscle was divided by blunt dissection to reveal the carotid artery. The carotid artery was dissected free of connective tissue and the vagus nerve and enclosed in a polythene prosthesis. The brachiocephalicus muscle was sutured dorsal to the now enclosed artery. The wound was closed taking care that the line of sutures did not overlie the prosthesis. Repeated percutaneous puncture of the artery was possible for periods of up to 18 months.
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10.1080/00480169.1986.35353
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pubmed_539_21530
|
OBJECTIVE
The aim of this study was to assess the reliability of a diagnostic protocol, the incremental challenge test (ICT), for patients with and without a history of adverse reactions to local anesthetics (LAs) or other drugs, to select an LA that could be safely used.
STUDY DESIGN
The ICT was performed on 432 subjects, 314 female and 118 male. Four hundred thirty-two challenges were carried out with LAs that were free of adrenaline and preservatives. Chi-square analysis was performed to evaluate the existence of different predispositions to ICT positivity among subjects of the 4 categories studied.
RESULTS
Four hundred fifteen tests were completed with no clinical events occurring. The analysis did not show any significant difference (chi-square = 6.17; P >.05).
CONCLUSIONS
Our results confirm that immunoglobulin E-mediated reactions to LAs are uncommon and that the ICT offers safety and specificity in diagnosing adverse reactions to LAs, allowing for the selection of a safe and reliable LA.
|
10.1067/moe.2001.113348
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pubmed_1051_12595
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Protein engineering and enzyme immobilization strategies have produced numerous biocatalysts for modern industrial applications. In this study, we have also used these two strategies for improving the operational stability and catalytic efficiency of serine protease from Pseudomonas aeruginosa. The enzyme serine protease was truncated to separate its trypsin-like domain from the PDZ1 and PDZ2 domains. The truncated trypsin-like domain was expressed in Escherichia coli BL21, and its catalytic activity and thermostability were estimated. Later this trypsin-like domain was immobilized with 2% Na-alginate. The immobilized domain showed 10°C increase in optimum temperature compared to its free counterpart. Kinetic studies showed two-folds increased Vmax of the immobilized domain. Likewise, the Km value of this domain was 11.5 folds lower compared to the free trypsin-like domain. The catalytic efficiency (Kcat /Km ) of the immobilized enzyme also elevated to 311 folds. Additionally, the immobilized trypsin-like domain remained active in the presence of surfactants (Triton-X 100, SDS, and Tween-40) and metal ions (Mg2+ , Ca2+ , Na+ , and Zn2+ ). It also efficiently removes gelatin layer from X-ray film and hair from sheepskin. Thus, the immobilized trypsin-like domain of serine protease, with increased thermostability and catalytic efficiency, is operationally more stable than the soluble truncated trypsin-like domain.
|
10.1002/prot.26323
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pubmed_800_15766
|
AIMS
The effect of oxygen on the survival of Torulaspora delbrueckii and Kluyveromyces thermotolerans during mixed culture fermentations in grape juice with Saccharomyces cerevisiae was investigated.
METHODS AND RESULTS
Fermentations were carried out in two simple fermentation systems differing in the availability of oxygen. At low available oxygen conditions, T. delbrueckii and K. thermotolerans began to die off after two days of mixed culture fermentation. In filtrates from 2-day-old mixed cultures, single cultures of T. delbrueckii and K. thermotolerans survived and actively produced ethanol to concentrations of approx. 65 and 70 g l-1, respectively, at low available oxygen conditions. Oxygen clearly increased the survival time and decreased the death rate of T. delbrueckii and K. thermotolerans in mixed cultures, whereas it did not affect the growth and survival of S. cerevisiae.
CONCLUSION
Our results show that the deaths of T. delbrueckii and K. thermotolerans in mixed cultures at low available oxygen conditions are not due to toxic metabolites produced by the yeasts but rather to the lack of oxygen. Furthermore, they indicate that T. delbrueckii and K. thermotolerans are less tolerant to low available oxygen conditions than S. cerevisiae.
SIGNIFICANCE AND IMPACT OF THE STUDY
Our study reveals new knowledge on the mechanisms underlying the succession of yeasts during wine fermentations. This knowledge may be of importance when creating defined, mixed starter cultures for the controlled production of wines with a wide range of flavour compositions.
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10.1046/j.1365-2672.2001.01426.x
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pubmed_955_15718
|
We report the cloning and expressing of rat natriuretic peptide receptor-C (NPR-C), which binds naturally occurring and synthetic ligands with higher affinity than human NPR-C. Using rat/human hybrids and site-directed mutagenesis, we identified residue 188, Ala for rat and Ile for human, which modulates hormone binding. Orthologous mutagenesis at position 188 for either rNPR-C or hNPR-C results in a complete reversal of the pharmacology. To our knowledge, this is the first example of a single transmembrane domain receptor for which a single residue dictates the ligand binding properties; previous examples are limited to seven transmembrane receptors.
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pubmed_955_15718
|
pubmed_126_19178
|
The severity of asthma can be graded from mild intermittent to severe persistent. Airway inflammation is a feature of persistent asthma. We compared several markers of inflammation in mucosal biopsies and bronchoalveolar lavage fluid (BAL fluid) from 12 healthy control subjects, 24 patients with intermittent asthma, and 18 patients with mild-to-moderate persistent asthma. Epithelial shedding, eosinophil (EG2-positive cells), and activated T-cell (UCHL1) counts in biopsies, and ECP levels in BAL fluids were significantly increased in patients with intermittent asthma by comparison with control subjects and this increase was significantly greater for patients with persistent asthma. Alveolar macrophage activation (percentage of hypodense cells) and the thickness of the basement membrane were significantly increased in asthmatic subjects as compared with controls but there was no difference between the two asthmatic groups. Hyaluronic acid levels in BAL fluids were significantly increased in patients with persistent asthma by comparison with control subjects and patients with intermittent asthma. Mast cell numbers (toluidine blue) in biopsies and histamine or levels in BAL fluids were similar in the three groups. This study shows that airways inflammation is present in patients with intermittent asthma but to a lesser extent than in patients with persistent asthma.
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10.1164/ajrccm.157.2.96-08040
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pubmed_602_897
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A 29-year-old male was found dead lying in a pool of blood inside a community toilet locked from inside. The individual is alleged to have committed suicide by cutting his throat with a safety razor blade, which was found at the scene by the investigating police authority. The deceased, as per his relatives, was suffering from depression for the last few days.
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10.1016/j.forsciint.2003.12.020
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pubmed_453_6829
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Microdialysis studies were conducted on prenatally saline-treated and prenatally cocaine-treated rats, either as pups (10-30 days old) or young adults (40-190 days old), to study the effects of prenatal cocaine exposure on the mesolimbic dopamine (DA) system. In the n. accumbens of saline-treated rats, basal dialysate concentrations of DA were similar in pups and adults; however, the levels of DA metabolites, DOPAC, HVA, and the serotonin metabolite, 5-HIAA, were markedly lower in pups. In pups, prenatal cocaine exposure led to basal dialysate levels of DA in the n. accumbens that were twice control levels; however, there was no difference in response to a period of intermittent tail pinch or an acute injection of cocaine (20 mg/kg). In the adult, basal levels of DA, DOPAC, HVA and 5-HIAA in n. accumbens did not differ across prenatal treatments. However, in prenatally cocaine-treated adults a cocaine injection led to an enhanced rise in extracellular DA compared to controls. In frontal cortex of adult rats, basal levels of DA, DOPAC and HVA did not differ across prenatal treatments; however, basal levels of 5-HIAA in this region were significantly elevated in prenatal-cocaine rats. No group differences were observed in the frontal cortex in response to either tail pinch or cocaine. Thus prenatal cocaine exposure produces an increase in basal extracellular DA in the n. accumbens of pups which returns to normal with aging. While this initial difference normalizes, prenatal cocaine exposure induces other persistent changes in adulthood.
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10.1016/s0006-8993(96)00959-6
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pubmed_749_6688
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Transplanted neurons derived from stem cells have been proposed to improve function in animal models of human disease by various mechanisms such as neuronal replacement. However, whether the grafted neurons receive functional synaptic inputs from the recipient's brain and integrate into host neural circuitry is unknown. Here we studied the synaptic inputs from the host brain to grafted cortical neurons derived from human induced pluripotent stem cells after transplantation into stroke-injured rat cerebral cortex. Using the rabies virus-based trans-synaptic tracing method and immunoelectron microscopy, we demonstrate that the grafted neurons receive direct synaptic inputs from neurons in different host brain areas located in a pattern similar to that of neurons projecting to the corresponding endogenous cortical neurons in the intact brain. Electrophysiological in vivo recordings from the cortical implants show that physiological sensory stimuli, i.e. cutaneous stimulation of nose and paw, can activate or inhibit spontaneous activity in grafted neurons, indicating that at least some of the afferent inputs are functional. In agreement, we find using patch-clamp recordings that a portion of grafted neurons respond to photostimulation of virally transfected, channelrhodopsin-2-expressing thalamo-cortical axons in acute brain slices. The present study demonstrates, for the first time, that the host brain regulates the activity of grafted neurons, providing strong evidence that transplanted human induced pluripotent stem cell-derived cortical neurons can become incorporated into injured cortical circuitry. Our findings support the idea that these neurons could contribute to functional recovery in stroke and other conditions causing neuronal loss in cerebral cortex.
|
10.1093/brain/aww347
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pubmed_271_4677
|
We report a surgical case of descending colon cancer with abdominal wall abscess. A 72-year-old man was admitted to a hospital because of left lower abdominal mass with slight pain. An abdominal CT showed a left lower abdominal wall abscess adjacent to the descending colonic wall thickening. We diagnosed an abdominal wall abscess due to descending colon cancer or colon diverticulitis. The abscess was drained under local anesthesia releasing foul-smelling pus and air. After abscess drainage and general improvement in his condition, we conducted subtotal colectomy with lymph node dissection and excision of abdominal wall abscess cavity. Pathological findings indicated moderately differentiated adenocarcinoma of the descending colon (pT4, pN0, sH0, sP0, sM0, fStage II). The carcinoma had invaded the abdominal wall and transverse colon, but the cancer cells were not shown in the abdominal wall abscess cavity. In abdominal wall abscess treatment, colon cancer should be considered as a potential underlying cause. CT proved useful for assessing the status of the tumor and the abscess. We conducted a radical operation for descending colon cancer after the drainage for abdominal wall abscess.
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pubmed_271_4677
|
pubmed_450_23662
|
BACKGROUND
The prevalence of significant obstructive coronary artery disease with complex lesions is high in patients who have low extremity artery disease (LEAD). However, intermediate- or long-term cardiovascular prognosis of LEAD patients undergoing percutaneous transluminal angioplasty (PTA) remains poor. Accordingly, prophylactic coronary revascularization may modify short- and long-term cardiovascular outcomes of LEAD patients receiving PTA. Because myocardial ischemic symptoms are often masked in LEAD and the accuracy of non-invasive stress tests is usually limited, a high-quality randomized controlled trial aimed at the investigation of the prognostic role of coronary evaluation strategies before PTA is warranted.
METHODS/DESIGN
The proposed study is designed as a prospective, multi-center, open-label, superiority, randomized controlled trial. The study is conducted in high-volume centers for PTA and coronary revascularization in Taiwan. To meet the inclusion criteria, the patients must be at least 20 years old, have known LEAD, and have been admitted for elective PTA. We plan to enroll 450 participants who are randomly allocated to a routine group (routine coronary angiography without a previous non-invasive stress test before PTA) and a selective group (selective coronary angiography based on the results of non-invasive stress tests before PTA) with 1:1 ratio. Besides, we expect to enroll about 250 additional participants, who are not willing to be randomly assigned, in the registration group. The choice of revascularization procedure depends on the operator's or cardiovascular team's suggestion and the patient's decision. Clinical follow-up will be performed 30 days after PTA and every 6 months until the end of the 1-year follow-up for the last randomly assigned participant. The primary endpoint is the composite major adverse cardiac event on long-term follow-up. Pre-specified secondary and other endpoints are also evaluated. Those assessing biomarkers and clinical endpoints are all blinded after assignment to interventions.
DISCUSSION
The results of the trial will, for the first time, support better decision-making for coronary evaluation before PTA in LEAD. If favorable, routine coronary angiography followed by revascularization will improve cardiovascular outcomes in LEAD patients undergoing PTA.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT02169258 (registered on 21 June 2014); registry name: Routine Coronary Catheterization in Low Extremity Artery Disease Undergoing Percutaneous Transluminal Angioplasty (PIROUETTE-PTA).
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10.1186/s13063-016-1237-0
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pubmed_1078_169
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The dispersion and initial transport of Cryptosporidium oocysts from fecal pats were investigated during artificial rainfall events on intact soil blocks (1,500 by 900 by 300 mm). Rainfall events of 55 mm h(-1) for 30 min and 25 mm h(-1) for 180 min were applied to soil plots with artificial fecal pats seeded with approximately 10(7) oocysts. The soil plots were divided in two, with one side devoid of vegetation and the other left with natural vegetation cover. Each combination of event intensity and duration, vegetation status, and degree of slope (5 degrees and 10 degrees ) was evaluated twice. Generally, a fivefold increase (P < 0.05) in runoff volume was generated on bare soil compared to vegetated soil, and significantly more infiltration, although highly variable, occurred through the vegetated soil blocks (P < 0.05). Runoff volume, event conditions (intensity and duration), vegetation status, degree of slope, and their interactions significantly affected the load of oocysts in the runoff. Surface runoff transported from 10(0.2) oocysts from vegetated loam soil (25-mm h(-1), 180-min event on 10 degrees slope) to up to 10(4.5) oocysts from unvegetated soil (55-mm h(-1), 30-min event on 10 degrees slope) over a 1-m distance. Surface soil samples downhill of the fecal pat contained significantly higher concentrations of oocysts on devegetated blocks than on vegetated blocks. Based on these results, there is a need to account for surface soil vegetation coverage as well as slope and rainfall runoff in future assessments of Cryptosporidium transport and when managing pathogen loads from stock grazing near streams within drinking water watersheds.
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10.1128/AEM.70.2.1151-1159.2004
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pubmed_71_6882
|
Reporting in Nature Cell Biology, Lin and Wang (2017) show that bacterial methyl metabolism impacts host mitochondrial dynamics and lipid storage in C. elegans. The authors propose a model whereby bacterial metabolic products regulate a nuclear hormone receptor that promotes lipid accumulation through expression of a secreted Hedgehog-like protein.
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10.1016/j.devcel.2017.05.010
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pubmed_40_12499
|
Edwardsiella ictaluri is the etiologic agent of enteric septicemia of catfish, which causes substantial losses in catfish aquaculture. To determine pathogen-host interactions, previous studies have used the green fluorescence protein (GFP) gene. Here, the pEI2 plasmid of E. ictaluri isolate I49 was tagged using a Tn10-GFP-kan cassette to create the green fluorescence-expressing derivative I49-gfp. The Tn10-GFP-kan insertion site was mapped by plasmid sequencing to 663 bp upstream of open reading frame 2 and appeared to be at a neutral site in the plasmid. Purification of the pEI2::GFPKan plasmid and mobilization into E. coli resulted in GFP expression. The isolated pEI2::GFPkan plasmid was used to retransform the wild type I49 isolate (ensuring a single Tn10-GFP-kan insertion) and an independent E. ictaluri isolate, S97-73-3. The wild type and the green fluorescent-tagged strains were compared for modulation of pathogenicity in channel catfish Ictalurus punctatus by immersion challenge. A significant reduction in mortalities occurred for the I49GFPkan strain as compared to its isogenic parent, but no difference was observed between the S97-73-3GFPkan strain and the S97-73-3 wild type. This GFP-tagged plasmid will be useful for determining the effects that the pEI2::GFPkan plasmid has on virulence and host-pathogen interactions between E. ictaluri isolates.
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10.3354/dao02610
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pubmed_302_4055
|
The nature and severity of pre-operative memory deficits observed in unilateral temporal lobe epilepsy depend upon a number of variables. Among these variables, age of seizure onset seems to be important. The age at which the lesion is sustained could modify the normal functional organization of the brain. Many studies have examined the effect of age of onset on the severity of memory deficits but have seldom focused on the nature of such deficits (verbal/nonverbal) as a function of epileptic focus laterality. This study investigates the effect of age of onset on the nature and severity of memory impairments. Fifty-six epileptics with unilateral temporal lobe epilepsy and 20 normal subjects were administered a neuropsychological evaluation. Four groups of patients were constituted: left or right temporal lobe epilepsy with early (0-5 years) or late (10 years and over) age of seizure onset. The early group showed major verbal and nonverbal memory deficits. The late group presented minor specific deficits: essentially verbal deficits with left temporal lobe seizures and nonverbal deficits with right temporal lobe seizures. These results may be interpreted in the framework of ontogenesis theories of hemispheric specialization.
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10.1016/s0028-3932(02)00012-x
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pubmed_601_7999
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The effect of physostigmine on the loss of consciousness and respiratory depression induced in rabbits by flunitrazepam, 1 mg/kg, was studied to demonstrate whether the restoration of consciousness and respiration rate results from an increase in central cholinergic activity or from an interference by physostigmine with specific binding of flunitrazepam to its receptors. Physostigmine, 0.1-0.4 mg/kg iv, caused a dose-related reversal of consciousness and respiration rate within 15 min of its injection, which lasted 15-30 min depending on the dose. This was associated with peak inhibition of acetylcholinesterase (AChE) in the frontal cortex and medulla, at 15 min, ranging from 35-51%. The analeptic effect of physostigmine in flunitrazepam-treated rabbits was prevented by pretreatment with scopolamine, 1 mg/kg. The effective dose range for physostigmine, 3-12 mumol/kg, is close to concentrations of this agent that inhibit activity in solubilized preparations of AChE from rabbit cortex, 1-3 X 10(-8) M. However, physostigmine, 10(-9) -10(-4) M, failed to displace 3H flunitrazepam from specific binding sites on membranes prepared from rabbit cerebral cortex. It is concluded that physostigmine antagonizes the somnolence and respiratory depression induced by benzodiazepines by restoring cholinergic transmission to normal levels. The effective dose range of physostigmine is small, and serious side effects from overdose can occur as a result of excess cholinergic activity at neuromuscular synapses.
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10.1097/00000542-198602000-00020
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pubmed_93_25526
|
The assessment of bone marrow involvement (BMI) is important for accurate prognostication and deciding the appropriate therapy in patients with lymphoma. Conventional bilateral iliac crest biopsies (ILBMBs) have many limitations. F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is a useful investigative tool for detecting BMI. F-18 FDG PET/CT data for 97 patients with either non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) were analyzed. ILBMB was performed 7-10 days later. A final diagnosis of BMI was made in 38/97 patients on the basis of composite criteria derived from both FDG PET/CT and ILBMB results. ILBMB detected BMI in 29/38 patients, 2/5 patients with HL, 27/33 patients with NHL, 19/25 patients with aggressive NHL, and 8/8 patients with indolent NHL with a sensitivity of 76%, 40%, 82%, 76%, and 100%, respectively. FDG PET/CT was true positive for BMI in 5/5 patients with HL and 29/33 patients with NHL, comprising 25/25 patients with aggressive NHL and 4/8 patients with indolent NHL, with a sensitivity of 100%, 88%, 100%, and 50%, respectively. FDG PET/CT performed better than ILBMB in cases of HL and aggressive NHL, but its sensitivity was poor in cases of indolent lymphoma. In addition, FDG PET/CT had a very high negative predictive value approaching 100% in HL and aggressive NHL, which might help in avoiding negative ILBMBs.
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10.3109/10428194.2011.593273
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pubmed_391_13974
|
BACKGROUND
Cardioplegic solutions have been used to enhance myocardial preservation during cardiac surgery. The benefits derived from preventing myocardial ischemia with cardioplegic solutions may, however, be countered by tissue damage that occurs when the myocardium is reperfused with oxygenated blood. Furthermore, cardioplegia-induced endothelial dysfunction may contribute to depressed myocardial function postoperatively. The endothelium of coronary arteries and vein grafts is damaged by crystalloid cardioplegic solutions. There is less known about the effects of cardioplegic solutions on the microvasculature.
METHODS AND RESULTS
The hypothesis that microvascular damage occurs following perfusion with hyperkalemic, crystalloid, cardioplegic solutions and blood reperfusion, leading to decreased blood flow and increased neutrophil accumulation, was tested in a model system. Intravital microscopic observations were performed during a 20-minute perfusion of the hamster cremaster muscle with cardioplegic solutions (10 degrees C) via the femoral artery with the iliac occluded and during a subsequent 2-hour blood reperfusion period (iliac open). Arteriolar vasoconstriction (27% decrease in diameter, p less than 0.05) and a 25% decrease in the density of perfused capillaries (p less than 0.05) occurred during reperfusion in hamsters receiving crystalloid cardioplegic solution (16 meq K+) compared to control hamsters (no cardioplegic solution given). Neutrophils accumulated on venular endothelium in treated animals (250% increase, p less than 0.05) and extravascularly (myeloperoxidase levels 2.0 +/- 0.4 U/g versus 1.3 +/- 0.3 U/g in control, p less than 0.05). The addition of adenosine (10(-4) M) and albumin (2 g%) to the cardioplegic perfusate, accompanied by the administration of adenosine (10(-4) M) during reperfusion, produced arteriolar vasodilation (34% diameter increase, p less than 0.05) and inhibited extravascular neutrophil accumulation (myeloperoxidase level of 1.5 +/- 0.2 U/g, p greater than 0.05 versus control). Capillary perfusion, however, was still significantly diminished (28% decrease, p less than 0.05.)
CONCLUSIONS
We conclude that injury manifest by decreased microvascular blood flow and increased neutrophil accumulation in tissues occurs after perfusion with hypothermic, hyperkalemic, crystalloid cardioplegic solutions and blood reperfusion. Adenosine seems to partially attenuate this injury by dilating arterioles and decreasing extravascular neutrophil accumulation.
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10.1161/01.cir.84.6.2485
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pubmed_1105_14617
|
The outbreak of monkeypox in the Unites States in the summer of 2003 was the first occurrence of this smallpox-like disease outside of Africa. This limited human epidemic resulted from cross-infection of prairie dogs by imported African rodents. Although there were no human fatalities, this outbreak illustrates that monkeypox is an emerging natural infection and a potential biological weapon. We characterized a virulence factor expressed by monkeypox (monkeypox inhibitor of complement enzymes or MOPICE). We also compared its structure and regulatory function to homologous complement regulatory proteins of variola (SPICE) and vaccinia (VCP). In multiple expression systems, 5-30% of MOPICE, SPICE, and VCP consisted of function-enhancing disulfide-linked homodimers. Mammalian cells infected with vaccinia virus also expressed VCP dimers. MOPICE bound human C3b/C4b intermediate to that of SPICE and VCP. Cofactor activity of MOPICE was similar to VCP, but both were approximately 100-fold less efficient than SPICE. SPICE and VCP, but not MOPICE, possessed decay-accelerating activity for the C3 and C5 convertases of the classical pathway. Additionally, all three regulators possessed heparin-binding capability. These studies demonstrate that MOPICE regulates human complement and suggest that dimerization is a prominent feature of these virulence factors. Thus, our data add novel information relative to the functional repertoire of these poxviral virulence factors. Furthermore, targeting and neutralizing these complement regulatory active sites via mAbs is a therapeutic approach that may enhance protection against smallpox.
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10.4049/jimmunol.176.6.3725
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pubmed_1112_2484
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Most theories attempting to explain the coexistence of species in local communities make fundamental assumptions regarding whether neighbors exhibit competitive, neutral, or positive resource-use interactions; however, few long-term data from naturally assembled plant communities exist to test these assumptions. We utilized a 13-year experiment consisting of factorial removal of three shrub species (Vaccinium myrtillus, V. vitis-idaea, and Empetrum hermaphroditum) and factorial removal of two functional groups (tree roots and feather mosses) to assess how neighbors affect N acquisition and growth of each of the three shrub species. The removal plots were established on each of 30 lake islands in northern Sweden that form a natural gradient of resource availability. We tested the hypotheses that: (1) the presence of functionally similar neighbors would reduce shrub N acquisition through competition for a shared N resource; (2) the removal of functional groups would affect shrub N acquisition by altering the breadth of their niches; and (3) soil fertility would influence the effects of neighbor removals. We found that the removal of functionally similar neighbors (i.e., other shrub species) usually resulted in higher biomass and biomass N, with the strength of these effects varying strongly with site fertility. Shrub species removals never resulted in altered stable N isotope ratios (delta(15)N), suggesting that the niche breadth of the three shrubs was unaffected by the presence of neighboring shrub species. In the functional group removal experiment, we found positive effects of feather moss removal on V. myrtillus biomass and biomass N, and negative effects on E. hermaphrotium N concentration and V. vitis-idaea biomass and biomass N. Tree root removal also caused a significant shift in foliar delta(15)N of V. myrtillus and altered the delta(15)N, biomass, and biomass N of E. hermaphroditum. Collectively, these results show that the resource acquisition and niche breadth of the three shrub species are often affected by neighbors, and further that both the identity of neighbors and site fertility strongly determine whether these interactions are positive, negative, or neutral. These findings have implications for understanding species coexistence and the reciprocal relationships between productivity and species diversity in this ecosystem.
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10.1890/11-1877.1
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pubmed_882_14319
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Methicillin resistance creates a major obstacle for treatment of Staphylococcus aureus infections. The resistance gene, mecA, is carried on a large (20 kb to > 60 kb) genomic island, staphylococcal cassette chromosome mec (SCCmec), that excises from and inserts site-specifically into the staphylococcal chromosome. However, although SCCmec has been designated a mobile genetic element, a mechanism for its transfer has not been defined. Here we demonstrate the capture and conjugative transfer of excised SCCmec. SCCmec was captured on pGO400, a mupirocin-resistant derivative of the pGO1/pSK41 staphylococcal conjugative plasmid lineage, and pGO400::SCCmec (pRM27) was transferred by filter-mating into both homologous and heterologous S. aureus recipients representing a range of clonal complexes as well as S. epidermidis. The DNA sequence of pRM27 showed that SCCmec had been transferred in its entirety and that its capture had occurred by recombination between IS257/431 elements present on all SCCmec types and pGO1/pSK41 conjugative plasmids. The captured SCCmec excised from the plasmid and inserted site-specifically into the chromosomal att site of both an isogenic S. aureus and a S. epidermidis recipient. These studies describe a means by which methicillin resistance can be environmentally disseminated and a novel mechanism, IS-mediated recombination, for the capture and conjugative transfer of genomic islands.
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10.1111/mmi.13340
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pubmed_847_25760
|
Background
Adolescent obesity, a risk factor for cardiorenal morbidity in adulthood, has reached epidemic proportions. Obesity-related glomerulopathy (ORG) has an early reversible stage of hyperfiltration. Age-appropriate formulae for eGFR, which are standardized to ideal body surface area (BSA) and provide assessment of kidney function in ml/min/1.73 m2, may underestimate prevalence of early ORG. We investigated whether adjusting eGFR to actual BSA more readily identifies early ORG.
Methods
We studied a cohort of 22,417 young individuals, aged 12-21 years, from a New York metropolitan multi-institutional electronic health records clinical database. eGFR was calculated in two ways: BSA-standardized eGFR, and absolute eGFR. Hyperfiltration was defined above a threshold of 135 ml/min per 1.73 m2 or 135 ml/min, respectively. The prevalence of hyperfiltration according to each formula was assessed in parallel to creatinine clearance.
Results
Serum creatinine values and hyperfiltration prevalence according to BSA-standardized eGFR were similar, 13%-15%, across body mass index (BMI) groups. The prevalence of hyperfiltration determined by absolute eGFR differed across BMI groups: underweight, 2%; normal weight, 6%; overweight, 17%; and obese, 31%. This trend paralleled the rise in creatinine clearance across BMI groups.
Conclusions
Absolute eGFR more readily identifies early ORG than the currently used formulae, which are adjusted to a standardized BSA and are not representative of current population BMI measures. Using absolute eGFR in clinical practice and research may improve the ability to identify, intervene, and reverse early ORG, which has great importance with increasing obesity rates.
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10.34067/KID.0005312021
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pubmed_302_16109
|
1. Collagen characteristics were compared in the tibiotarsus and humerus from 103 females and 38 males aged 68 to 72 weeks from the G6 generation of lines of laying hen selected for resistance or susceptibility to osteoporosis (high and low bone index (BI) lines). 2. Selection over the latest generation resulted in further divergence in the breaking strengths of humerus (from 12.3 to 21.8%) and tibia (from 22.3 to 37.3%) in hens. Males also showed line differences in bone strengths. 3. Plasma pyridinoline concentration was higher in hens in the low BI line, suggesting a greater rate of bone resorption in this line. 4. There were few differences between the lines in collagen and calcium concentrations in humerus and tibiotarsus cortical bone. 5. There were no differences between the lines in either sex in reduced immature collagen cross-link content of humerus or tibiotarsus. 6. Mature collagen cross-link content was higher in the high BI line in the male humerus but this effect was not apparent in the male tibiotarsus nor in either bone in the females. 7. Pyrrolic cross-link contents were higher in the high BI line in the female humerus and tibiotarsus and in the male tibiotarsus. 8. Over both lines combined, there were positive correlations between humeral and tibiotarsal pyrrole contents and strengths in females and between tibiotarsal pyrrole content and strength in males. 9. It is concluded that an increase in cross-linking, particularly pyrrolic cross-linking, in the collagen matrix contributes in part to the improvement in bone strength in the high BI line.
|
10.1080/00071660120109962
|
pubmed_499_16069
|
Purpose
Gartland Type 1 supracondylar humerus fractures are stable, non-displaced injuries treated with non-operative management. This systematic review was performed to gather evidence on the optimal form of immobilization to treat these fractures.
Methods
The review process was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. An electronic search was performed in November 2020. Articles were eligible if they included children less than 18 years old, with non-displaced supracondylar fractures, treated non-operatively. Randomized trials, quasi-experimental trials, and prospective cohort studies were included. Outcomes of interest included fracture displacement, pain control, time to return to normal activities, return of range of motion (ROM), child/parent satisfaction, adverse events, and cost. Risk of bias was assessed using the Newcastle-Ottawa scale, Rob-2, and the ROBINS tools.
Results
After duplicate records were removed, 525 records were evaluated with 9 studies meeting the inclusion criteria and 5 reporting clinical outcomes. The studies were heterogenous, in intervention and outcomes, and all at moderate risk of bias. Within the available evidence there were no cases of fracture displacement. Two small studies suggested that cuff and collar treatment provided inadequate pain control and delay in return to normal activities, compared to posterior splints. Two randomized control trials (RCTs) suggested that soft fiberglass casts reduced appointment time and increased parent satisfaction, compared to traditional casts. No studies directly compared posterior splints to circumferential casts.
Conclusion
There is insufficient high-quality evidence to determine the optimal conservative treatment for patients with Gartland type 1 supracondylar fractures. Level of Evidence Level II systematic review of Level II studies.
Systematic Review Registration
[PROSPERO], identifier [CRD42020144616].
|
10.3389/fped.2022.863985
|
pubmed_444_18952
|
OBJECTIVE
Surgical trainees are subject to pressure from variety of stakeholders to secure board certification from the American Board of Surgery (ABS). To meet these expectations, trainees must pass a written qualifying exam (QE) and an oral certifying exam (CE) within 7 years of completing general surgery residency. Board certification outcomes for candidates who fail either the QE or CE examination are not well characterized, but this information could help candidates, policymakers, and other stakeholders make informed decisions about how to respond to examination failure.
METHODS
We retrospectively examined ABS records for all surgeons who completed general surgery residency from 2000 to 2013 and attempted general surgery board certification.
RESULTS
Among 14,483 surgeons who attempted general surgery certification, 13,566 (94%) passed both the QE and CE within the 7-year certification window. Of those who did ultimately obtain certification, 97% passed the QE within 2 attempts and 97% passed the CE within 2 attempts. For those who failed either the QE or the CE twice, 67% ultimately obtained certification.
CONCLUSIONS
Most surgeons who obtained ABS general surgery board certification did so within 2 attempts at each board examination. Candidates who fail either examination twice are less likely to achieve board certification.
|
10.1016/j.jsurg.2020.08.047
|
pubmed_27_8763
|
The nuclear matrix is an integral part of nuclear structure which undergoes a profound reorganization during the cell cycle reflecting major changes in functional requirements. This includes the processes of DNA replication and gene expression at interphase and partitioning of the nuclear contents during mitosis. Using a monoclonal antibody (mAb2A) which specifically stains a novel nuclear meshwork which reorganizes during the cell cycle in Drosophila, we have initiated a study to: 1) more closely analyze this structural reorganization; 2) clone and characterize the antigens recognized by this antibody; and 3) isolate other interacting proteins in order to gain insight into the regulation of this process. The mAb2A-labeled structure changes from what appears as a diffuse meshwork at interphase to a distinct spindle-like scaffold at prophase. Since at metaphase the microtubules of the mitotic apparatus co-localize with the mAb2A spindle structure, a model is considered whereby the nuclear mAb2A-labeled scaffolding reorganizes during the cell cycle to provide a guide for the establishment of the mitotic apparatus. The mAb2A has identified two separate antigens, each of which shows similar distribution patterns. One of these antigens has been partially cloned and contains an unusual tandem ser-thr kinase domain. The association of this kinase homologue with a nuclear scaffold which reorganizes during the cell cycle suggests that it may be involved in regulating changes in nuclear architecture during the cell cycle and/or in mediating the downstream consequences of such changes.
|
10.1002/(sici)1097-4644(19960301)60:3<289::aid-jcb1>3.0.co;2-s
|
pubmed_1048_24038
|
BACKGROUND
TNF-α plays an important role in the pathogenesis of Legionella pneumophila (Lp)-induced pneumonia. Patients undergoing anti-TNF-α therapy are at an increased risk of Lp infection. Lp infects both phagocytic and non-phagocytic cells such as airway epithelial cells; however, the role of TNF-α in airway epithelial cells is unknown.
METHODS
Human airway epithelial cell line NCI-H292 was infected with Lp NUL1 strain. After infection, both intracellular growth of Lp and cell death were evaluated after treating the cells with or without TNF-α. Apoptosis was examined by performing activated caspase-3/7 staining and by using a pan-caspase inhibitor.
RESULTS
Lp infected and replicated in NCI-H292 cells in a time-dependent manner, and TNF-α treatment of Lp-infected NCI-H292 cells inhibited Lp replication. Inhibitory effects of TNF-α on Lp replication were suppressed after treatment with a TNF-α-neutralizing antibody. Lp infection increased extracellular lactate dehydrogenase levels and decreased the number of living cells. Increased number of Lp-infected NCI-H292 cells showed caspase-3/7 activation, indicating they underwent apoptosis. TNF-α treatment inhibited Lp replication by increasing the apoptosis of NCI-H292 cells.
CONCLUSIONS
Thus, our results suggested that airway epithelial cells were involved in the pathogenesis of Lp infection and that TNF-α played a protective role by inhibiting the intracellular replication of Lp and by increasing the apoptosis of Lp-infected airway epithelial cells. However, Lp infection should be investigated further in patients undergoing anti-TNF-α therapy who develop pneumonia.
|
10.1016/j.jiac.2016.09.010
|
pubmed_1044_6717
|
Deoxyribonuclease II (DNase II) is one of the earliest enzymes discovered in the history of biochemistry. Its role in apoptosis and development has been documented with great detail in eukaryotes. Prior in silico analyses showed its complete absence in bacterial genomes, with the exception of single bacterial genus: Burkholderia. It is therefore considered to be a eukaryotic enzyme. Here we show that the presence of DNase II is not limited to Burkholderia, as we find over one hundred DNase II-like sequences spanning 90 bacteria species belonging to 54 different genera and seven phyla. The majority of the significant hits (85%) come from Bacteroidetes and Proteobacteria phyla. Sequence analyses reveal that bacterial DNase II-like proteins possess a signature catalytic motif of eukaryotic DNase II. In phylogenetic analyses, we find that bacterial DNase II-like proteins are divided into two distinct clades. Our structural analyses reveal high levels of similarity between experimentally determined crystal structures of recombinant Burkholderia thailandensis DNase II and candidate bacterial DNase II-like proteins. We also biochemically show that Chromobacterium violaceum cell lysate possesses acidic DNase II-like activities. Collectively, our results indicate that DNase II has deeper evolutionary roots than previously thought. We argue that either some prokaryotic lineages have undergone losses of DNase II genes, resulting in rare conservation, or some lineages have acquired DNase II genes from eukaryotes through lateral gene transfer. We also discuss the possible involvement of DNase II as a part of an anti-phage defense system in bacteria.
|
10.1016/j.ympev.2022.107554
|
pubmed_732_6077
|
Proteobacteria use quorum sensing to regulate target gene expression in response to population density. Quorum sensing (QS) is achieved via so-called signalling molecules and the best-studied QS signalling system uses N-acyl homoserine lactones (AHLs). This study aimed to identify and characterize the production of AHLs by a bacterium ND03 isolated from a Malaysian tropical rainforest waterfall. Molecular identification showed that ND03 is a Pantoea sp. closely related to Pantoea rodasii. We used Chromobacterium violaceum CV026, an AHL biosensor for preliminary AHL production screening and then used high resolution triple quadrupole liquid chromatography-mass spectrometry, to confirm that P. rodasii strain ND03 produced N-(3-oxo-hexanoyl)-L-homoserine lactone (3-oxo-C6-HSL). To the best of our knowledge, this is the first report for such a discovery in P. rodasii strain ND03.
|
10.3390/s140509145
|
pubmed_281_12521
|
The combination of KRAS G12C inhibitors with EGFR inhibitors has reproducibly been shown to be beneficial. Here, we identify another benefit of this combination: it effectively inhibits both wild-type and mutant RAS. We believe that targeting both mutant and wild-type RAS helps explain why this combination of inhibitors is effective.
|
10.1038/s41698-022-00329-w
|
pubmed_804_12205
|
The solid-liquid interface is of great interest because of its highly heterogeneous character and its ubiquity in various applications. The most fundamental physical variable determining the strength of the solid-liquid interface is the solid-liquid interfacial tension, which is usually measured according to the contact angle. However, an accurate experimental measurement and a reliable theoretical prediction of the contact angle remain lacking because of many practical issues. Here, we propose a first-principles-based simulation approach to quantitatively predict the contact angle of an ideally clean surface using our recently developed multiscale simulation method of density functional theory in classical explicit solvents (DFT-CES). Using this approach, we simulate the surface wettability of a graphene and graphite surface, resulting in a reliable contact angle value that is comparable to the experimental data. From our simulation results, we find that the surface wettability is dominantly affected by the strength of the solid-liquid van der Waal's interaction. However, we further elucidate that there exists a secondary contribution from the change of water-water interaction, which is manifested by the change of liquid structure and dynamics of interfacial water layer. We expect that our proposed method can be used to quantitatively predict and understand the intriguing wetting phenomena at an atomistic level and can eventually be utilized to design a surface with a controlled hydrophobic(philic)ity.
|
10.1021/acs.jpclett.8b00466
|
pubmed_417_6533
|
Oxytocin (OT) release from synaptosomes isolated from the thoracic (T) and lumbosacral (LS) regions of the spinal cord was evoked by 56 mM potassium chloride (KCl). The release mechanism was shown to be a calcium dependent process. The ability of high KCl to evoke OT release from isolated nerve terminals in a calcium dependent manner provides additional support for the role of OT as a neurotransmitter in the spinal cord.
|
10.1016/0024-3205(94)00495-1
|
pubmed_483_5423
|
Potato chips and french fries were analyzed by high performance liquid chromatography and thin layer chromatography for cholesterol and (β-sitosterol oxidation products. Chips stored for 150 d at 23°C in unopened foil bags contained no detectable sitosterol oxidation products, but those held at 40°C contained 7α-hydroxysitosterol, 7β-hydroxysitosterol, and sitosterol (β-epoxide only after an extended storage of 95 d. French fries as purchased contained sterol α- and β-epoxides, and 7α- and 7β-hydroxysterols. These sterol oxidation products were present in repeat samples from five different fast food restaurants. Ingestion of sterol oxides from potato chips is unlikely, whereas ingestion of sterol oxides from french fries is possible.
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10.4315/0362-028X-48.2.158
|
pubmed_11_7627
|
UNLABELLED
Hallux rigidus is a term used to describe painful, limited motion and localized arthritis at the hallux metatarsophalangeal (MTP) joint. With early hallux rigidus, a dorsal cheilectomy can decrease pain and improve motion. With later stage disease, a hallux MTP arthrodesis is commonly chosen to decrease pain, sacrificing motion by fusing the hallux MTP joint. We present an alternative technique to arthrodesis for late stage hallux rigidus-the modified oblique Keller capsular interposition arthroplasty (MOKCIA). With this operation, the dorsal capsule of the hallux MTP joint is interposed into the joint, offering pain relief without sacrificing range of motion.
LEVEL OF EVIDENCE
Level V, expert opinion.
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10.1177/1071100714523590
|
pubmed_732_6049
|
Successful heart-lung complex transplantation was performed in a 48-year-old man. During the postoperative period, M. tuberculosis infection was diagnosed, and the treatment subsequently started. One year after, the patient was urgently hospitalized due to myocardial infarction. However, despite the best efforts, the patient died. Antituberculosis treatment is recommended to all the patients with confirmed active tuberculosis. Treatment of tuberculosis in transplant recipients is similar to that of the general population, with the exclusion of rifamycins in the regimen and longer duration of treatment.
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pubmed_732_6049
|
pubmed_398_22238
|
The influence of protein synthesis on the regulation of the first meiotic division was studied in pig oocytes. We show that histone H1 kinase activity gradually increases during in vitro culture of pig oocytes, reaching maximum in metaphase I stage after 24 hr of culture. However, in the presence of the protein synthesis inhibitor cycloheximide, histone H1 kinase is not activated during the whole culture period, and after 24 hr it is approximately at the same level as in prophase-stage oocytes. The gradual increase in phosphorylation of six proteins of molecular weights 39, 48, 53, 66, 96, and 120 kDa, observed during the first 24 hr of culture, was not detected when cycloheximide was added to the culture medium. Similarly, the decrease in phosphorylation of a 90-kDa protein was not seen in cycloheximide-treated oocytes. On the other hand, the levels of both MPF components, p34cdc2 and cyclin B, which were found to be nearly constant during the first meiotic division, were not influenced by cycloheximide treatment as revealed by Western blotting. The process of germinal vesicle breakdown (GVBD) was totally blocked by cycloheximide. The condensation of chromatin, however, was not influenced, suggesting that GVBD and chromosome condensation could be regulated independently. The different degrees of MPF activation involved in these processes, as well as the nature of the protein(s) which must be synthesized for triggering GVBD, are discussed.
|
10.1002/mrd.1080410110
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pubmed_883_796
|
AIMS
To compare the blood toxicology of heroin overdose cases and morphine positive homicide victims.
DESIGN
Analysis of coronial cases.
SETTING
Sydney, Australia. Cases A total of 705 cases of death due to opioid toxicity and 28 morphine positive homicide cases (1 January 1998-31 December 2002).
FINDINGS
There was no significant difference between the median morphine concentrations of the overdose and homicide groups (0.50 versus 0.45 mg/l). The overdose group was more likely to have blood alcohol (OR 3.21) present, but less likely to have methadone (OR 0.26) and cannabis (OR 0.04). There was a significant negative correlation between blood morphine and alcohol concentrations among the overdose group (rho = -0.32), but not among the homicide group (rho = -0.03). Independent predictors of a higher blood morphine concentration were a lower alcohol concentration and a higher methadone concentration.
CONCLUSIONS
Morphine concentrations per se are not diagnostic of overdose. The study confirms the salience of concomitant alcohol consumption in such events.
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10.1111/j.1360-0443.2007.01980.x
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pubmed_652_2017
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We applied Charlson comorbidity index (CCI) stratification on a large cohort of chronic myeloid leukemia (CML) very elderly patients (>75 years) treated with imatinib, in order to observe the impact of concomitant diseases on both compliance and outcome. One hundred and eighty-one patients were recruited by 21 Italian centers. There were 95 males and 86 females, median age 78.6 years (range 75-93.6). According to Sokal score, 106 patients were classified as intermediate risk and 55 as high risk (not available in 20 patients). According to CCI stratification, 71 patients had score 0 and 110 a score ≥ 1. Imatinib standard dose was reduced at start of therapy (200-300 mg/day) in 68 patients independently from the evaluation of baseline comorbidities, but based only on physician judgement: 43.6% of these patients had score 0 compared to 34% of patients who had score ≥ 1. Significant differences were found in terms of subsequent dose reduction (39% of patients with score 0 compared to 53% of patients with score ≥ 1) and in terms of drug discontinuation due to toxicity (35% of patients with score 0 vs 65% of patients with score ≥ 1). We did not find significant differences as regards occurrence of hematologic side effects, probably as a consequence of the initial dose reduction: 39% of patients with score 0 experienced grade 3/4 hematologic toxicity (most commonly anemia) compared to 42% of patients with score ≥ 1. Independently from the initial dose, comorbidities again did not have an impact on development of grade 3/4 non-hematologic side effects (most commonly skin rash, muscle cramps and fluid retention): 62% of patients with score 0 compared to 52.5% of patients with score ≥ 1. Notwithstanding the reduced dose and the weight of comorbidities we did not find significant differences but only a trend in terms of efficacy: 66% of patients with score 0 achieved a CCyR compared to 54% of patients with score ≥ 1. Comorbidities appeared to have an impact on median OS (40.8 months for patients with score 0 vs 20.16 months for patients with score ≥ 1) on EFS and on non-CML death rate. Our results suggest that treatment of very elderly CML patients might be influenced by personal physician perception: evaluation at baseline of comorbidities according to CCI should improve initial decision-making in this subset of patients.
|
pubmed_652_2017
|
pubmed_1089_23894
|
The aim of this study was to investigate the feasibility of using visible near-infrared (VisNIR) diffuse reflectance spectroscopy (DRS) as an easy, inexpensive, and rapid method to predict compost enzymatic activity, which traditionally measured by fluorescein diacetate hydrolysis (FDA-HR) assay. Compost samples representative of five different compost facilities were scanned by DRS, and the raw reflectance spectra were preprocessed using seven spectral transformations for predicting compost FDA-HR with six multivariate algorithms. Although principal component analysis for all spectral pretreatments satisfactorily identified the clusters by compost types, it could not separate different FDA contents. Furthermore, the artificial neural network multilayer perceptron (residual prediction deviation=3.2, validation r(2)=0.91 and RMSE=13.38 μg g(-1) h(-1)) outperformed other multivariate models to capture the highly non-linear relationships between compost enzymatic activity and VisNIR reflectance spectra after Savitzky-Golay first derivative pretreatment. This work demonstrates the efficiency of VisNIR DRS for predicting compost enzymatic as well as microbial activity.
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pubmed_1089_23894
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pubmed_202_20367
|
The long-term effect of 1 alpha-hydroxyvitamin D3 and calcium lactate in osteoporotic patients was evaluated by the bone mineral density (BMD) measured at the distal one third and one sixth of the radius and by the vertebral fracture rate. Forty-five osteoporotic patients medicated for 1 to 13 years (treated group) and 11 osteoporotic patients with no medication for 1 to 3 years (control group) were compared. The BMD of the treated group remained unchanged for the first 4 (one-third site) and 6 years (one-sixth site), followed by significant decreases, whereas that of the control group decreased significantly at the second and third year. The effect on BMD was more prominent in the patients with lower initial BMD. The vertebral fracture rate of the treated group was significantly less than that in the control group at the third year. No serious side effects were recognized. Overall, we believe 1 alpha-hydroxyvitamin D3 with calcium supplement can be considered a safe and effective agent for long-term use in osteoporotic patients.
|
10.3928/0147-7447-19921201-05
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pubmed_304_16326
|
OBJECTIVE
To review the literature on the limitations and consequences of packed red blood cell transfusions, with particular attention to critically ill patients.
METHODS
The PubMed database of the National Library of Medicine was searched to find published articles on the indications, clinical utility, limitations, and consequences of red blood cell transfusion, especially in critically ill patients.
RESULTS
Several dozen papers were reviewed, including case series, meta-analyses, and retrospective and prospective studies evaluating the physiological effects, clinical efficacy, and consequences and complications of transfusion of packed red blood cells. Most available data indicate that packed red blood cells have a very limited ability to augment oxygen delivery to tissues. In addition, the overwhelming preponderance of data accumulated in the past decade indicate that patients receiving such transfusions have significantly poorer outcomes than do patients not receiving such transfusions, as measured by a variety of parameters including, but not limited to, death and infection.
CONCLUSIONS
According to the available data, transfusion of packed red blood cells should be reserved only for situations in which clear physiological indicators for transfusion are present.
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pubmed_304_16326
|
pubmed_587_6719
|
Over the last 10-15 years, scientific knowledge related to the neurobiology of pain systems has expanded substantially. Today the pain system cannot be regarded as static, but one that can undergo substantial neuroplastic changes. These can be increased effectiveness of synaptic transmission, up and/or down regulation of peptides in the dorsal root ganglion, increased and/or decreased expression of receptors. The manifestations of such changes can be pain evoked by normally non-painful stimuli (allodynia) or a heightened reaction to painful stimuli (hyperalgesia). Such reactions are seen in neuropathic pain conditions and are difficult to treat with conventional therapies. In the near future, greater knowledge of the neurobiology of pain may lead to new and more specific analgesics.
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pubmed_587_6719
|
pubmed_588_20545
|
The detailed characterization of protein N-glycosylation is very demanding given the many different glycoforms and structural isomers that can exist on glycoproteins. Here we report a fast and sensitive method for the extensive structure elucidation of reducing-end labeled N-glycan mixtures using a combination of capillary normal-phase HPLC coupled off-line to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and TOF/TOF-MS/MS. Using this method, isobaric N-glycans released from honey bee phospholipase A2 and Arabidopsis thaliana glycoproteins were separated by normal-phase chromatography and subsequently identified by key fragment ions in the MALDI-TOF/TOF tandem mass spectra. In addition, linkage and branching information were provided by abundant cross-ring and "elimination" fragment ions in the MALDI-CID spectra that gave extensive structural information. Furthermore, the fragmentation characteristics of N-glycans reductively aminated with 2-aminobenzoic acid and 2-aminobenzamide were compared. The identification of N-glycans containing 3-linked core fucose was facilitated by distinctive ions present only in the MALDI-CID spectra of 2-aminobenzoic acid-labeled oligosaccharides. To our knowledge, this is the first MS/MS-based technique that allows confident identification of N-glycans containing 3-linked core fucose, which is a major allergenic determinant on insect and plant glycoproteins.
|
10.1021/ac0614137
|
pubmed_1072_23848
|
Using the Vividness of Visual Imagery Questionnaire we selected 14 high-scoring and 15 low-scoring healthy participants from an initial sample of 111 undergraduates. The two groups were matched on measures of age, IQ, memory and mood but differed significantly in imagery vividness. We used fMRI to examine brain activation while participants looked at, or later imagined, famous faces and famous buildings. Group comparison revealed that the low-vividness group activated a more widespread set of brain regions while visualising than the high-vividness group. Parametric analysis of brain activation in relation to imagery vividness across the entire group of participants revealed distinct patterns of positive and negative correlation. In particular, several posterior cortical regions show a positive correlation with imagery vividness: regions of the fusiform gyrus, posterior cingulate and parahippocampal gyri (BAs 19, 29, 31 and 36) displayed exclusively positive correlations. By contrast several frontal regions including parts of anterior cingulate cortex (BA 24) and inferior frontal gyrus (BAs 44 and 47), as well as the insula (BA 13), auditory cortex (BA 41) and early visual cortices (BAs 17 and 18) displayed exclusively negative correlations. We discuss these results in relation to a previous, functional imaging study of a clinical case of 'blind imagination', and to the existing literature on the functional imaging correlates of imagery vividness and related phenomena in visual and other domains.
|
10.1016/j.cortex.2017.09.014
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pubmed_348_8045
|
Ultramicroscopy, a novel optical tomographic imaging modality related to fluorescence microscopy, allows to acquire cross-sectional slices of small specially prepared biological samples with astounding quality and resolution. However, scattering of the fluorescence light causes the quality to decrease proportional to the depth of the currently imaged plane. Scattering and beam thickness of the excitation laser light cause additional image degradation. We perform a physical simulation of the light scattering in order to define a quantitative function of image quality with respect to depth. This allows us to establish 3D-volumes of quality information in addition to the image data. Volumes are acquired at different orientations of the sample, hence providing complementary regions of high quality. We propose an algorithm for rigid 3D-3D registration of these volumes incorporating voxel quality information, based on maximizing an adapted linear correlation term. The quality ratio of the images is then used, along with the registration result, to create improved volumes of the imaged object. The methods are applied on acquisitions of a mouse brain and mouse embryo to create outstanding three-dimensional reconstructions.
|
10.1007/978-3-540-75759-7_87
|
pubmed_1033_12840
|
OBJECTIVES
We analyse the concordance between Gleason scores on prostate biopsies diagnostic of adenocarcinoma and radical prostatectomy specimens.
METHODS
We reviewed the charts of 214 patients who underwent radical prostatectomy between January 1992 and November 2002. We calculated the percentage of correct diagnosis, understaging and overstaging for individual Gleason and for groups with scores between 2-4, 5-6, 7 and 8-10. We performed the statistical analyses of concordance for the groups using the kappa weighted index (< 0.4 low reliability, 0.4-0.75 good reliability; > 0.75 excellent reliability).
RESULTS
41 patients were excluded. The percentages of right diagnosis, understaging and overstaging for the remainder 173 were 32.3%, 44% and 23.7% respectively for individual Gleason scores, and 52.6%, 32.4% and 15% respectively for grouped Gleason scores. Statistical analysis resulted in a kappa weighted index of 0.52, a result which did not vary after excluding patients treated with neoadjuvant hormonal therapy
CONCLUSIONS
In our series, the statistical correlation obtained for grouped Gleason scores is good. However, understaging is the biggest problem for prostate biopsies diagnostic of adenocarcinoma when compared with definitive pathologic results on the specimen. Besides, and in opposition, more than 50% of our patients deemed as less differentiated (Gleason score 7 and 8-10) presented lower grades in the specimen. Both limitations should be taken into consideration when therapeutic options are exposed to our patients.
|
pubmed_1033_12840
|
pubmed_210_4387
|
Infectious diseases are key drivers of wildlife populations and agriculture production, but whether and how climate change will influence disease impacts remains controversial. One of the critical knowledge gaps that prevents resolution of this controversy is a lack of high-quality experimental data, especially in marine systems of significant ecological and economic consequence. Here, we performed a manipulative experiment in which we tested the temperature-dependent effects on Atlantic salmon (Salmo salar) of sea lice (Lepeophtheirus salmonis)-a parasite that can depress the productivity of wild-salmon populations and the profits of the salmon-farming industry. We explored sea-louse impacts on their hosts across a range of temperatures (10, 13, 16, 19, and 22 °C) and infestation levels (zero, 'low' (mean abundance ± SE = 1.6 ± 0.1 lice per fish), and 'high' infestation (6.8 ± 0.4 lice per fish)). We found that the effects of sea lice on the growth rate, condition, and survival of juvenile Atlantic salmon all worsen with increasing temperature. Our results provide a rare empirical example of how climate change may influence the impacts of marine disease in a key social-ecological system. These findings underscore the importance of considering climate-driven changes to disease impacts in wildlife conservation and agriculture.
|
10.1038/s41598-020-74948-3
|
pubmed_279_16509
|
Cultured intact fetal membrane disks initially produced high levels of prostaglandin E2 (PGE2) on the fetal and maternal sides which declined during four days of culture. The transfer of a bolus of PGE2 from the fetal side to the maternal side of the membrane ranged from 1% to 3% after 24 hours of culture, and was a minimum over the period of 48-72 hours from the start of the incubation. To assess the handling of PGE2 synthesized by the amnion, 3H-arachidonic acid was incorporated into cultured amnion and into the amnion side of cultured intact fetal membrane disks. Labelled amnion released 3H-PGE2 on both sides of the tissue, whereas similarly labelled cultured intact fetal membrane only had detectable levels of 3H-PGE2 on the fetal side. It was calculated that no more than 9.7 +/- 1.4% of the PGE2 synthesised by the amnion crossed to the maternal side of the membrane without being metabolised during the transfer through the membrane. These results are consistent with similar indirect methods which suggested that PGE2 from the amnion may have only a limited role in human labor, and indicates the importance of using appropriate culture systems to investigate intra-uterine prostaglandin production.
|
10.3109/00016349309058155
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pubmed_536_19560
|
Mutations of the p53 gene are relatively rare in synovial sarcoma. With this in mind we investigated the potential of the HDM2 antagonist, nutlin-3 to induce p53 activity in synovial sarcoma cells lines. Nutlin-3 effectively promoted p53 stability which was concurrent with the activation of p53 target genes, growth arrest and apoptosis. Analysis of synovial sarcoma cells showed that p53 is effectively stabilized in response to DNA damage; however transcriptional activation of p53 target genes p21 and HDM2 is abrogated. Co-immunoprecipitation studies showed the presence of high levels of p53-HDM2 complexes in doxorubicin but not nutlin-3 treated cells suggesting that HDM2 association is responsible for the loss of p53 activity. Our results support the hypothesis that p53 function is suppressed by aberrant HDM2 activity and suggest the possibility of targeting the p53-HDM2 regulatory axis as a therapeutic strategy in synovial sarcoma.
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10.1016/j.canlet.2008.10.030
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pubmed_19_14836
|
BACKGROUND
Carotid ultrasound screening (CUS) has been recommended for cardiovascular disease risk prediction, but its effectiveness in clinical practice is unknown. The purpose of this study was to prospectively determine the effects of office-based CUS on physician decision making and patient health-related behaviors.
METHODS
Physicians from five nonacademic, community practices recruited patients aged ≥40 years with ≥1 cardiovascular disease risk factor. Abnormal results on CUS (AbnlCUS) were defined as carotid intima-media thickness >75th percentile or carotid plaque presence. Subjects completed questionnaires before and immediately after CUS and then 30 days later to determine self-reported behavioral changes. Odds ratios (ORs) for changes in physician management and patient health-related behaviors were determined from multivariate hierarchical logistic regression models.
RESULTS
There were 355 subjects (mean age, 53.6 ± 7.9 years; mean number of risk factors, 2.3 ± 0.9; 58% women); 266 (74.9%) had AbnlCUS. The presence of AbnlCUS altered physicians' prescription of aspirin (P < .001) and cholesterol medications (P < .001). Immediately after CUS, subjects reported increased ability to change health-related behaviors (P = .002), regardless of their test results. Subjects with AbnlCUS reported increased cardiovascular disease risk perception (OR, 4.14; P < .001) and intentions to exercise (OR, 2.28; P = .008), make dietary changes (OR, 2.95; P < .001), and quit smoking (OR, 4.98; P = .022). After 30 days, 34% increased exercise frequency and 37% reported weight loss, but these changes were not predicted by the CUS results. AbnlCUS modestly predicted reduced dietary sodium (OR, 1.45; P = .002) and increased fiber (OR, 1.55; P = .022) intake.
CONCLUSIONS
Finding abnormal results on CUS had major effects on physician but not patient behaviors.
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10.1016/j.echo.2011.02.013
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pubmed_189_19002
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Neutrophil extracellular traps (NETs) have been described as a potential trigger of severe COVID-19. NETs are known as extracellular DNA fibers released by neutrophils in response to infection. If the host is unable to balance efficient clearance of NETs by dornases (DNases), detrimental consequences occur. Elevated levels of NETs in COVID-19 patients are associated with higher risk of morbid thrombotic complications. Here, we studied the level of NET markers and DNase activity in a cohort of COVID-19 patients compared to healthy controls. Our data confirmed an increased level of NET markers in the plasma of COVID-19 patients, with a higher level in male compared to female patients. At the same time, there was an increased DNase activity detectable in COVID-19 patients compared to healthy controls. Importantly, there was a negative correlation of DNase activity with the age of male patients. The antimicrobial peptide LL-37, which is known to stabilize NETs against DNase degradation, is embedded in NETs upon severe acute respiratory syndrome coronavirus-2-infection. The LL-37 plasma level correlates with the NET-marker level in male COVID-19 patients, indicating a potential role of LL-37 in the risk of NET-associated thrombosis in male COVID-19 patients by stabilizing NETs against DNase degradation. In conclusion, our data identify two potential risk factors of elderly male patients which may lead to inefficient NET degradation and a subsequently higher risk of NET-associated thrombosis during COVID-19: reduced DNase activity and an increased LL-37 level.
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10.1159/000521594
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pubmed_628_1271
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The preparation of d,l-phenylalanine via amidocarbonylation of benzyl chloride with acetamide and CO/H(2) is described. The rate of the reaction is dependent upon the CO pressure below 250 bar, but independent of the hydrogen pressure. A reaction temperature of 100 degrees C gives optimum yields. A relatively large amount of the catalyst, Co(2)(CO)(8), is needed for complete conversion because of inhibition caused by hydrogen chloride which is formed during the reaction. Addition of NaHCO(3) removes HCl as insoluble NaCl, resulting in improved conversion and selectivity of the reaction. It also allows the use of a stoichiometric amount of acetamide, whereas a 2- to 3-fold excess of acetamide is needed for complete conversion of benzyl chloride without NaHCO(3). Amidocarbonylation of benzyl alcohol gave d,l-phenylalanine in only 8% yield.
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10.1021/jo951802t
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pubmed_411_9919
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We have previously shown that phenyl saligenin phosphate (PSP), an organophosphorus compound which is classed as a weak inhibitor of acetylcholinesterase, triggered cytotoxicity in mitotic and differentiated H9c2 cardiomyoblasts. The aim of this study was to assess whether sublethal concentrations of PSP could disrupt the morphology of differentiating rat H9c2 cardiomyoblasts and human-induced pluripotent stem-cell-derived cardiomyocyte progenitor cells (hiPSC-CMs) and to assess the underlying cytoskeletal changes. PSP-induced changes in protein expression were monitored via Western blotting, immunocytochemistry, and proteomic analysis. PSP-mediated cytotoxicity was determined by measuring MTT reduction, LDH release, and caspase-3 activity. Sublethal exposure to PSP (3 μM) induced morphological changes in differentiating H9c2 cells (7, 9, and 13 days), reflected by reduced numbers of spindle-shaped cells. Moreover, this treatment (7 days) attenuated the expression of the cytoskeletal proteins cardiac troponin I, tropomyosin-1, and α-actin. Further proteomic analysis identified nine proteins (e.g., heat shock protein 90-β and calumenin) which were down-regulated by PSP exposure in H9c2 cells. To assess the cytotoxic effects of organophosphorus compounds in a human cell model, we determined their effects on human-induced pluripotent stem-cell-derived cardiomyocyte progenitor cells. Chlorpyrifos and diazinon-induced cytotoxicity (48 h) was evident only at concentrations >100 μM. By contrast, PSP exhibited cytotoxicity in hiPSC-CMs at a concentration of 25 μM following 48 h exposure. Finally, sublethal exposure to PSP (3 μM; 7 days) induced morphological changes and decreased the expression of cardiac troponin I, tropomyosin-1, and α-actin in hiPSC-CMs. In summary, our data suggest cardiomyocyte morphology is disrupted in both cell models by sublethal concentrations of PSP via modulation of cytoskeletal protein expression.
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10.1021/acs.chemrestox.0c00100
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pubmed_829_4947
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Macrophage tracking by magnetic resonance imaging (MRI) with iron oxide nanoparticles has been developed during the last decade for numerous diseases of the CNS. Experimental studies on animal models were confirmed by first clinical applications of MRI technology of brain macrophages for multiple sclerosis, ischemic stroke lesions, and tumors. As activated macrophages act in concert with other immune competent cells, this innovative MRI approach provides new functional data on the immune reaction in these CNS diseases. The MRI detection of brain macrophages defines precise spatial and temporal patterns of macrophage involvement that helps to characterize individual neurological disorders. This approach is being explored as an in vivo marker for the clinical diagnosis of cerebral lesion activity, in experimental models for the prognosis of disease development, and to determine the efficacy of immunomodulatory treatments under clinical evaluation. Comparative brain imaging follow-up studies of blood-brain barrier leakage by MRI with gadolinium-chelates, microglia activation by positron emission tomography with radiotracer ligand PK11195 and MRI detection of macrophage infiltration provide more precise information about the pathophysiological cascade of inflammatory events in cerebral diseases. Such multimodal characterization of the inflammatory events should help in the monitoring of patients, in defining precise time intervals for therapeutic interventions, and in developing and evaluating new therapeutic strategies.
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10.1016/j.nurt.2007.05.005
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pubmed_196_14568
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Simultaneous isolation of ions of disparate mass-to-charge (m/z) ratios is demonstrated via appropriately timed pulsing of entrance and exit ion mirrors in an electrostatic linear ion trap (ELIT) mass spectrometer. Manipulation of the voltages of the entrance and exit mirrors, referred to as "mirror switching", has been demonstrated as a method in which ions can be both captured and isolated. High resolution isolation (>35 000) was previously demonstrated by selective gating of trapping electrodes to avoid ion lapping while closely spaced ions could continue to separate [ Johnson et al. Anal. Chem. 2019 , 91 , 8789 ]. In this work, we demonstrate that advantage can be taken of the ion lapping phenomenon in an ELIT to enable the simultaneous isolation of ions of disparate m/z ratios using mirror switching. This process is demonstrated with minimal ion loss using isotopologues of three carborane compounds ranging in m/z from 320 to 1020. Simultaneous isolation is demonstrated with the isolation of two and three peaks in separate isotopic distributions as well as with the isolation of alternating isotopologues within the same distribution. Such simultaneous isolation experiments are particularly useful when conducting experiments in which a mass calibrant is needed or when multiplexing in a tandem MS workflow.
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10.1021/acs.analchem.9b03560
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pubmed_552_3437
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The effects of dietary calcium, magnesium, and butterfat on intestinal function and flora in rats initiated with 1,2-dimethylhydrazine (DMH) were studied. Male weanling rats were assigned to six isocaloric diets that varied in their levels of calcium and magnesium (0.25% Ca with 0.05% Mg, 1.0% Ca with 0.05% Mg, or 0.625% Ca with 0.50% Mg) and butterfat (5% or 20%). One-half of the rats in each treatment were injected subcutaneously with DMH weekly for four weeks. This short-term exposure to DMH increased colonic ornithine decarboxylase (ODC) activity and the mass of cecal contents. Ingestion of the high levels of either calcium or magnesium depressed colonic ODC activity and depressed apparent absorption of organic matter, calcium, magnesium, and phosphorus. Ingestion of excess magnesium increased the mass of the cecal contents by twofold, caused hypertrophy of cecal walls, and increased the total amount of protein and total nitroreductase and beta-glucuronidase activity in the ceca of rats. Ingestion of supplemental calcium had less dramatic effects and increased the mass of cecal contents by only 28% and decreased the total amount of protein in the ceca. On the basis of their different effects on cecal microflora, magnesium appears to have less potential than does calcium as a protective agent against colon cancer.
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10.1080/01635589009514059
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pubmed_16_6410
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Neurons are extremely active cells and metabolize up to 20% of the oxygen that was consumed by the organism. Despite their highly oxygenic metabolism, neuronal cells have a lower capacity to neutralize the reactive oxygen species (ROS) that they generate or to which they are exposed. High levels of ROS can lead to accumulation of damage to various cellular macromolecules. One of the cellular macromolecules highly affected by intracellular as well as extracellular insults is DNA. Neurons are also highly differentiated, postmitotic cells that cannot be replenished after disease or trauma. Since neurons are irreplaceable and should survive as long as the organism does, they need elaborate defense mechanisms to ensure their longevity. This review article mainly focuses on certain mechanisms that contribute to neuronal longevity, and concentrates on the DNA damage response in neuronal cells. The various mechanisms of DNA repair are briefly described, and focus is on those mechanisms that are activated in neuronal cells following DNA damage. Evidence is presented to show that proper DNA damage response is critically important, not just for normal neuronal development but throughout the entire life of any organism. Defective DNA damage response in older human age can generate neurodegenerative disorders such as Alzheimer's or Parkinson diseases.
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10.1089/ars.2007.9.211
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pubmed_411_6257
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In view of the continuous resistance to antibacterial agents by bacteria and the existing problems of silver nanoparticles as an antibacterial agent, this study reports on the synthesis of pure zirconium oxide, silver oxide, and ZrO2-Ag2O nanoparticles by sol-gel method. The nanoparticles were analyzed and tested for their antibacterial activity against gram-positive bacteria of Bacillus subtilis, Streptococcus mutans, Staphylococcus aureus, and gram-negative of Escherichia coli, Pseudomonas aeruginosa, and Klebsiella oxytoca. X-ray diffraction showed the monoclinic ZrO2, cubic Ag2O, and peaks corresponding to ZrO2 and Ag2O in their mixed samples. Scanning electron microscopy showed spherically shaped nanoparticles while dynamic light scattering analysis showed ZrO2 (76 nm), Ag2O (50 nm), and ZrO2-Ag2O samples between 14 and 42 nm. The Fourier Transformed Infrared spectroscopy spectra of ZrO2 gave bands at 480 cm-1 to 750 cm-1 (M-O stretching) with Ag2O at 580 cm-1, while ZrO2-Ag2O samples showed bands at 760 cm-1. The screening by agar diffusion assay revealed a pronounced increase in the antibacterial activity of ZrO2-Ag2O against all the tested bacteria when compared with the pure ZrO2 and Ag2O. The improved antibacterial activity of ZrO2-Ag2O largely results from the chemical stability conferred on it by the ZrO2 as observed from the zeta potential measurement.
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10.1177/1559325820941374
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pubmed_543_15104
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This study evaluated bone and cementum regeneration following periodontal reconstructive surgery using recombinant human bone morphogenetic protein-2 (rhBMP-2) in six beagle dogs. Surgically created mandibular supraalveolar premolar tooth defects in contralateral jaw quadrants were randomly assigned to receive rhBMP-2 or control vehicle. Clinical defect height was prepared to 5 mm. rhBMP-2 was applied with synthetic bioerodable particles and autologous blood using 20 micrograms rhBMP-2 per 100 microliters implant volume. Flaps were advanced to submerge the teeth and sutured. The dogs were sacrificed 8 weeks postsurgery. Histometric recordings included defect height, height and area of alveolar bone regeneration, height of cementum regeneration, root resorption, and ankylosis. Group means, standard deviations, and P values are shown (Student t test; n = 6). Histometric defect height for rhBMP-2 and control defects was 3.7 +/- 0.3 and 3.9 +/- 0.4 mm, respectively (P = 0.446). Height of alveolar bone regeneration amounted to 3.5 +/- 0.6 and 0.8 +/- 0.6 mm for rhBMP-2 and control defects, respectively (P = 0.000). Corresponding values for bone area were 8.4 +/- 4.5 and 0.4 +/- 0.5 mm2, respectively (P = 0.006). Cementum regeneration was observed in all experimental defects (17/17) and in 15 out of 17 controls, averaging 1.6 +/- 0.6 and 0.4 +/- 0.3 mm for rhBMP-2 and control defects, respectively (P = 0.005). Small amounts of root resorption were seen in rhBMP-2 defects, whereas controls exhibited substantial resorption (0.2 +/- 0.1 and 1.1 +/- 0.3 mm, respectively; P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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10.1902/jop.1995.66.2.131
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pubmed_1027_14755
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A new radial enzyme diffusion (RED) method for the measurement of DNase activity in serum and urine is described. The sensitivity of the assay is in the range of 15.6-500 ng/ml. The assay is based on the hydrolysis of double-stranded (ds) DNA (or nucleosomes) in agarose. The specificity of the reaction for DNase I was established by showing that either EDTA in the reaction buffer or G-actin abolished DNase activity. Being a functional assay, RED has advantages over radioimmunoassay (RIA) or ELISA, since antigenic assays may also measure complexes of DNase with actin. This method was used to measure DNase activity in the sera and urine of lupus-prone mice (NZB/NZW F1 hybrids, aged 4-6 weeks). Serum DNase activity in these mice was significantly lower (mean 9 ng/ml) than in control, normal mice of the same age and sex (mean 37 ng/ml). Concentration of DNase in the urine of 4-6-week-old female NZB/NZW F1 hybrids (24 ng/ml) was significantly lower then in control mice (521 ng/ml). The RED method was used to measure the concentration of actin as the DNase inhibitor in serum. G-actin in the presence of ATP binds DNase and inhibits its nucleolytic activity. Since ATP is necessary for the actin inhibition of DNase I, this shows that there is actin as well as DNase I in the serum. Actin is not only ATP-dependent, but also heat-labile. Heating the sera for 10 min at 50 degrees C increases DNase activity. This is an alternative method for measuring the concentration of actin in the serum. An almost identical estimate of actin concentration in sera of normal mice was found from the difference of DNase activity in the presence or absence of ATP (mean actin concentration = 21 ng/ml) or from the difference of DNase activity in heated and non-heated serum (mean actin concentration 18 ng/ml). We were not able to demonstrate DNase inhibitors in the urine of either control or NZB/W F1 hybrid mice.
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10.1046/j.1365-2249.1997.3571249.x
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pubmed_312_597
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Five healthy male volunteers received over 60 sec a single intravenous injection of 400 mg of teicoplanin labelled with 41 microCi of 14C. Plasma and urine total radioactivity was measured up to 10 and 16 days, respectively. Teicoplanin was assayed in plasma and urine also by a microbiological method, with similar results. Pharmacokinetic parameters were estimated by model-independent analysis and the following mean values were obtained: elimination half-life 77 h; total body clearance 9.8 ml/h/kg; renal clearance 7.81 ml/h/kg; volume of distribution at steady-state 0.759 l/kg. Similar estimates were obtained by a compartmental analysis. A total of 80% of the administered dose was recovered in urine in 16 days; 2.7% of the dose was recovered in faeces collected for eight days after administration. The mean total recovery of the drug was 83 +/- 0.6%. The plasma and urine concentrations of teicoplanin observed after a single 400 mg iv dose exceeded the MIC for most pathogens for at least one day, and this suggests that a daily dosage regimen would be satisfactory for patients with normal renal function.
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10.1093/jac/21.suppl_a.23
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pubmed_661_21800
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In vascular smooth muscle, phorbol esters cause a slowly developing contraction and an associated transmembrane calcium flux, both of which are inhibited by dihydropyridine calcium channel antagonists. In the A7r5 cultured vascular cell line, we used the whole-cell voltage-clamp technique to identify voltage-dependent calcium conductances and investigate the effect of phorbol esters on that conductance having characteristic dihydropyridine sensitivity (slowly inactivating, high-threshold, "L-type"). With barium as the charge carrier, large-amplitude (100-800 pA) inward currents of two types were characterized by their kinetics and voltage dependence. With holding potential--80 mV, a rapidly inactivating, low-threshold current ("T-type") was activated by depolarizations above-40 mV and was maximal at -10 mV. With holding potential -30 mV, this component was inactivated, and a second slowly inactivating, high-threshold current was activated above -10 mV and was maximal at +10 to +20 mV. These currents are similar to the T-type and L-type currents previously described in vascular smooth muscle cells. When added to the bath, the active phorbol ester, 12-O-tetradecanoyl phorbol-13-acetate (100 nM) increased the slowly inactivating (L-type) current by 32 +/- 20% (n = 8, +/- SD). Phorbol-12,13-dibutyrate (100 nM) caused a similar effect, but the inactive phorbol, 4-alpha-phorbol (100 nM), did not. We conclude that at least two distinct calcium conductances are expressed in A7r5 vascular smooth muscle cells, and that the dihydropyridine-sensitive calcium conductance is acutely modulated by phorbol esters, presumably acting through stimulation of protein kinase C. Such modulation may play a role in increasing transmembrane calcium influx mediated by agonist-receptor interactions that lead to activation of protein kinase C and may help to sustain or amplify calcium-dependent cell responses.
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10.1161/01.res.62.5.1049
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pubmed_522_13702
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Data errors and marker allele frequency misspecification can lead to incorrect inference in linkage analysis. Here we demonstrate the effect of each on an allele-sharing statistic in a sample of sib pairs. In the context of relationship testing, we propose a new test that compares the sample genome-wide sib-pair allele sharing to its expectation and show that this test can detect the presence of large-scale data and model errors.
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10.1159/000081456
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pubmed_1025_1285
|
INTRODUCTION
Recent literature revealed good short-term results after microfracturing (MFX) of isolated focal cartilage defects in the knee joint. Study purpose was a long-term evaluation of patients who received MFX through a multimodal approach, correlating clinical scores and morphological pre- and postoperative MRI-scans.
MATERIALS AND METHODS
Between 2000 and 2007 158 patients were treated with MFX for focal femoral or tibial defects at our department. Patients with instabilities, secondary surgical intervention, patellofemoral lesions, a plica mediopatellaris or more than one cartilage defect site and age >55 were excluded. 15 patients were included. Minimum postoperative follow-up (FU) was 18 months (18-78 m). Mean age at surgery was 45 years (27-54), mean FU-interval 48 months (18-78 m). Male to female ratio was 9:6. For clinical assessment the Knee Osteoarthritis Ou tcome Score (KOOS) and Lysholm Score were used, radiological evaluation was performed with radiographs and 3Tesla-MRI.
RESULTS
Clinical knee function was rated good to excellent in 1 patient, fair in 2 and poor in 10 patients. 2/15 patients received full knee replacement due to insufficient cartilage repair through MFX during FU period. Evaluation of pre- and postoperative MRI showed good cartilage repair tissue in 1 (7.7%), moderate repair in 2 (15.4%) and poor fill in 10 patients (76.9%). In these 10 patients the defect size increased. Average defect size preoperatively was 187 mm(2) (range 12-800 mm(2)) and postoperatively 294 mm(2) (40-800 mm(2)). The KOOS-Pain averaged 60 (39-94), KOOS-Symptoms 60.6 (21-100), KOOS-ADL 69 (21-91), KOOS-Sports 35.7 (5-60) and KOOS-QUL 37.2 (6-81). The average Lysholm Score was 73.9 (58-94). 10 patients showed a varus leg axis deviation (Ø 5.9°), 3 had a neutral alignment. The alignment correlated positively with KOOS and especially with the Lysholm Score.
CONCLUSION
Our study demonstrated that MFX as a treatment option for cartilage defect in the knee did not show the anticipated clinical and radiological long-term results. In 12 of 15 patients the cartilage defect size had increased after MFX, in 2 patients indicating full-knee replacement. Especially those with a leg malalignment >5° in varus were more prone to suffer from an increase in defect size. In our cohort the clinical scores correlated with the radiological findings.
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10.1016/j.ejrad.2011.04.071
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pubmed_462_9238
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Long-chain polyunsaturated fatty acid (LCPUFA) composition of choline phosphoglycerides was measured in the plasma of 22 preterm infants at birth and at expected date of delivery (EDD). In a subgroup of 10 infants, data were also collected at regular intervals between birth and EDD. Levels at birth showed a positive correlation between arachidonic acid (AA) and birth weight, p less than 0.01, and between docosahexaenoic acid (DHA) and gestational age, p less than 0.01. Percentage compositions of both AA and DHA fell rapidly between preterm birth and expected date of delivery, at a time when they would remain high in utero. For AA, the mean value fell from 16.52 to 7.18%, and for DHA from 4.49 to 2.63%. Levels of DHA fell less in babies fed breast milk than in those fed formula milk, p less than 0.05, and levels of AA fell less in those requiring a large number of blood transfusions, p less than 0.05. The level of DHA fell more in those infants with intrauterine growth retardation, p less than 0.05. Although these nutrients share common metabolic pathways for their synthesis, they appear to be affected by different factors in both the fetus and the preterm infant. Low levels at this time may adversely affect brain and retinal development.
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10.1097/00005176-199204000-00011
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pubmed_290_22069
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Although the action site of wilforine is located in the muscle tissue of insects, the insecticidal mechanism of wilforine is not yet clear. This research explored the effects of wilforine on the calcium signaling pathway using the calcium imaging technique to reveal the insecticidal mechanism. It was confirmed that wilforine had strong cytotoxicity to Mythimna separata myocytes with the IC50 values of 25.14 and 19.65 mg/L using CCK-8 and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide methods, respectively. The morphological development of M. separata myocytes was also affected. The calcium imaging technique showed that the intracellular calcium ion concentration ([Ca2+]i) increased by 23.45% of the initial value after being treated with 100 nM wilforine. However, wilforine did not increase [Ca2+]i after the myocytes were preincubated with thapsigargin, and the [Ca2+]i could not be decreased by 50 μM ryanodine after being treated with 100 nM wilforine. These results indicated that the targets of wilforine are located in the sarcoplasmic reticulum, and ryanodine receptor (RyR) is an important action target of wilforine. Furthermore, wilforine can also activate the inositol triphosphate receptor (IP3R), which was confirmed through the use of 2-aminoethyl diphenylborinate, an inhibitor of IP3R. Connected with previous research studies, it can be concluded that wilforine affects the calcium signaling pathway by combining with RyR and IP3R, causing calcium dyshomeostasis, which results in insect paralysis and death.
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10.1021/acs.jafc.9b05592
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pubmed_990_10345
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Recurrent aphthae (or aphthoses) are the most frequent inflammatory lesions of the oral mucosa. Aphthae can clearly be defined, but may also be barely discernible from aphthoid erosions and ulcers of heterogeneous origin. Although a subject of molecular research, the etiopathogenesis of oral aphthoses is still unknown. However, the clinical differentiation of a "benign" type of aphthosis from a "pernicious" one, such as Behçet's disease (BD), is a diagnostic matter of great significance. BD has been found clinically in increasing numbers in central Europe and represents an (auto-)hyperimmune multisystem life-threatening vasculitis. In this disorder possible damage can occur to many visceral organs and/or the cerebrospinal system. The prognosis of BD may depend on the changing involvement of very different organs, as well as the early recognition of the disease per se. The most prominent feature is a multilesional aphthous stomatitis that is almost never absent during acute episodes of BD. Hence, the occurrence of this peculiar type of aphthosis strongly indicates an active BD. The plethora of other aphthoid lesions can be challenging to the diagnostic competence of all physicians and may confuse the correct recognition of the severity of the disease present. This review particularly details the wide range of diagnostic, therapeutic and prognostic aspects of the various oral aphthoses.
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10.1007/s001060050208
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pubmed_186_2243
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Sharp increases in atmospheric CO2 are resulting in ocean warming, acidification and deoxygenation that threaten marine organisms on continental margins and their ecological functions and resulting ecosystem services. The relative influence of these stressors on biodiversity remains unclear, as well as the threshold levels for change and when secondary stressors become important. One strategy to interpret adaptation potential and predict future faunal change is to examine ecological shifts along natural gradients in the modern ocean. Here, we assess the explanatory power of temperature, oxygen and the carbonate system for macrofaunal diversity and evenness along continental upwelling margins using variance partitioning techniques. Oxygen levels have the strongest explanatory capacity for variation in species diversity. Sharp drops in diversity are seen as O2 levels decline through the 0.5-0.15 ml l(-1) (approx. 22-6 µM; approx. 21-5 matm) range, and as temperature increases through the 7-10°C range. pCO2 is the best explanatory variable in the Arabian Sea, but explains little of the variance in diversity in the eastern Pacific Ocean. By contrast, very little variation in evenness is explained by these three global change variables. The identification of sharp thresholds in ecological response are used here to predict areas of the seafloor where diversity is most at risk to future marine global change, noting that the existence of clear regional differences cautions against applying global thresholds.
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pubmed_186_2243
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pubmed_1140_23938
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We used a newly generated antiserum specific for the Wnt receptor Frizzled9 to examine the distribution of this protein in the telencephalon. Previous studies showed expression of the mRNA for Frizzled9 in a medial high to lateral low gradient during cortical development 6. Our studies with the Frizzled9 antiserum supported this localization during mid-gestation mouse embryos. Later in gestation, the expression of Frizzled9 persisted in all cellular derivatives of the medial cortical neuroepithelium. From birth through adulthood, Frizzled9 continues to be expressed in the principal neuronal cells of the hippocampus. Interestingly, Frizzled9 was also expressed by astrocytic cells and dividing neuronal precursors in the adult dentate gyrus. Thus, Frizzled9 expression marks are a regional marker of medially derived cortical derivatives throughout rodent life and will be a useful marker in the study of regulation of cortical arealization.
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10.1016/j.devbrainres.2005.02.018
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pubmed_347_10889
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Olmsted syndrome is a rare congenital, sharply circumscribed transgredient palmoplantar keratoderma. It was first described by Olmsted in 1927. The diagnosis of this rare disease depends on clinical features like symmetrical involvement of keratoderma of the palms and soles and the symmetrical hyperkeratotic plaques around the body orifices. It starts in the neonatal period or in childhood. The disease has a slow but progressive and extremely disabling course. Treatment of Olmsted syndrome is often based on topical therapy with retinoic acid, corticosteroid, emollients, and keratolytics. The present paper describes a case of Olmsted syndrome and its treatment.
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10.1155/2012/927305
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pubmed_418_21790
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Pneumocystis pneumonia (PCP) is caused by the fungus Pneumocystis jirovecii, and its incidence has been on the rise in immunosuppressed patients without HIV. We performed a cross sectional study in patients with PCP and assessed demographic, clinical presentation and outcome measures such as mechanical ventilation and mortality differences between HIV and non-HIV patients. The two groups were statistically significantly different, with the HIV group being younger (45.5 years vs 55.9 years, p-value 0.001) and mostly composed of male patients (69% vs 31%, p-value <0.001). Also, the HIV patients had higher percentage of respiratory complaints (90% vs 68%, p-value 0.02) and lactate dehydrogenase elevation (73% vs 40%, p-value 0.001). In contrast, non-HIV patients had worse outcomes with higher incidence of invasive mechanical ventilation (23% vs 46%, p-value 0.005) and in-hospital mortality (13% vs 37%, p-value 0.002). These results reflect the literature and should raise awareness to a potentially fatal medical situation of increasing incidence.
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10.1016/j.pulmoe.2019.04.003
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pubmed_1055_6812
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The purpose of this work is to develop a mathematical model of energy balance and body weight regulation that can predict species-specific response to common pre-clinical interventions. To this end, we evaluate the ability of a previously published mathematical model of mouse metabolism to describe changes in body weight and body composition in rats in response to two short-term interventions. First, we adapt the model to describe body weight and composition changes in Sprague-Dawley rats by fitting to data previously collected from a 26-day caloric restriction study. The calibrated model is subsequently used to describe changes in rat body weight and composition in a 23-day cannabinoid receptor 1 antagonist (CB1Ra) study. While the model describes body weight data well, it fails to replicate body composition changes with CB1Ra treatment. Evaluation of a key model assumption about deposition of fat and fat-free masses shows a limitation of the model in short-term studies due to the constraint placed on the relative change in body composition components. We demonstrate that the model can be modified to overcome this limitation, and propose additional measurements to further test the proposed model predictions. These findings illustrate how mathematical models can be used to support drug discovery and development by identifying key knowledge gaps and aiding in the design of additional experiments to further our understanding of disease-relevant and species-specific physiology.
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10.1371/journal.pone.0155674
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pubmed_673_8535
|
To an increasing extent the total replacement of a hip joint damaged by disease or trauma is increasing in importance. Yet the implantation systems in use at the present time show defects which lead to increased rates of reoperation. In particular, the reactions at the implantation-tissue limiting surface must be specially mentioned. A number of technical parameters are therefore discussed which arise as possible causes for prosthesis clearance.
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pubmed_673_8535
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pubmed_346_16751
|
The vertebrate central nervous system (CNS) has been traditionally thought to be inaccessible for the passenger lymphocytes of the immune system. This does not seem to be the case: activated T-lymphocytes can readily cross the endothelial blood-brain barrier (BBB) and some glial cells, notably the astrocytes, seem to be programmed to act as most efficient and complex partners for antigen-specific T-lymphocytes. We used myelin basic protein (MBP) specific permanent rat T-lymphocyte lines as probes to assess the immune status of the CNS. These cells, upon activation in vitro, are able to transfer lethal, experimentally induced autoimmune-encephalomyelitis (EAE) to normal syngeneic recipients. Activated T-lymphocytes, but not resting ones, can break through the BBB irrespective of their antigen specificity. Immune surveillance of the CNS thus seems to be executed by activated T-lymphocytes. Having crossed the BBB, the activated T-cells interact with local glial cells by releasing factors, including interferon-gamma, which induced astrocytes to synthesize and express, on their membranes, class II major histocompatibility antigens (Ia determinants), which are critically required for immunogenic presentation of antigens to T-cells. Indeed, Ia-induced astrocytes of the CNS (and the Schwann cells of peripheral nerves) are efficient antigen presenter cells, which are able strongly to up-regulate antigen-reactive T-lymphocytes. In addition, it has recently been shown that at least some astrocytes are able to down-regulate immune cells. Some, but not all, astrocytes are capable of suppressing activation of T-cells. This suppression can be modulated by interferon-gamma, and is sensitive to irradiation. The question of whether suppression is mediated by direct cell-to-cell contact or via soluble mediators (e.g. apolipoprotein E) is under investigation. Astrocytes have been found to be most subtle regulators of immuno-competent T-cells. Most probably they are centrally involved in physiological immune reactivity of the CNS, and it will be tempting to learn how far glial cells are involved in transmitting regulatory signals between the immune and nervous systems.
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10.1242/jeb.132.1.43
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pubmed_521_585
|
Psychobiological studies of maternal behavior among non-primate mammals have arrived at several general conclusions that may aid in our understanding of human maternal behavior and in the clinical treatment of parenting disorders. The hormonal basis of maternal behavior arises during pregnancy and consists of a hormonal priming phase, extending over most of pregnancy, and a hormonal triggering phase at the end of pregnancy. Hormonal priming in several species depends upon estrogen, progesterone and prolactin, and hormonal triggering depends upon a decline in progesterone and an increase in estrogen, prolactin and oxytocin in different species. The onset of maternal behavior is hormonally based but postpartum maternal behavior in several species is based upon the stimulation that the mother receives from her young (i.e. is non-hormonally based). There is a transition period between these two phases soon after parturition during which contact with the young plays a crucial role in the maintenance of maternal behavior. The onset of maternal behavior may be viewed as the resolution of conflict between approach and withdrawal responses of females to their offspring.
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10.1111/j.1651-2227.1994.tb13259.x
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pubmed_552_1319
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Isolated hepatocyte suspensions were exposed to hypotonic and hypertonic stresses and serial cell volume measurements were made with an electronic particle size analyzer. With the exposure to hypotonic (160 mosM) buffer, hepatocytes swelled within 30-60 s as osomometers [relative volume (RV) = 1.44 +/- 0.08] and subsequently underwent regulatory volume decrease (RVD) back toward the resting (isotonic) level (1.16 +/- 0.05). This volume recovery was blocked by 65 mM extracellular K+ concentration and inhibited by barium (1 mM) and quinine (0.5 mM) but not by bumetanide (0.1 mM). Chloride depletion inhibited RVD by approximately 40% while 0.5 mM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) blocked the recovery by almost 90%. Calcium deprivation had no effect on RVD, nor did ouabain, amiloride, or sodium replacement. When exposed to buffer made hypertonic by addition of 200 mM sucrose, cells shrunk as osmometers (RV = 0.74 +/- 0.02) but did not exhibit regulatory volume increase (RVI). However, when cells that had first undergone RVD were reexposed to isotonic medium (relative hypertonic stress) RVI could be demonstrated from RV 0.77 +/- 0.17 to 0.91 +/- 0.20. This response was dependent on sodium, partially dependent on bicarbonate and chloride, and inhibited by the Na(+)-H+ exchange inhibitor amiloride (1 mM) but not by DIDS. Our findings suggest that RVD in rat hepatocytes is mediated by quinine- and barium-sensitive K+ conductance and DIDS-sensitive anion conductance, which is partly accounted for by Cl-; RVI is mediated by activation of Na(+)-H+ exchange coupled with a bicarbonate- and chloride-dependent but DIDS-insensitive process.
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10.1152/ajpgi.1990.258.2.G290
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pubmed_1069_9474
|
We have identified a novel ubiquitin conjugating enzyme gene, L-UBC, which maps to human Chromosome (Chr) 14q24.3. This is also the location of the major early onset familial Alzheimer's disease gene (FAD3). L-UBC encodes a protein that demonstrates homology to the yeast ubiquitin conjugating enzyme, UBC-4, and human UbcH5. Their functions are to ubiquitinate specific proteins targeted for degradation. The protein also exhibits very strong homology to a rabbit protein, E2-F1, which mediates p53 degradation driven by papilloma virus E6 protein in vitro. The accumulation of specific proteins that have undergone aberrant processing in neurofibrillary tangles and amyloid plaques is the classic pathological feature in brains of Alzheimer's disease patients. Abnormal ubiquitination has previously been suggested to play a role in the etiology of Alzheimer's disease. This gene therefore represents a plausible candidate gene for FAD3.
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10.1007/BF00354295
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pubmed_244_655
|
INTRODUCTION
The aim of this study was to describe core characteristics in a Danish population of rehabilitated traumatic spinal cord injury (SCI) patients.
METHODS
Retrospectively, data were extracted from a database on all traumatic patients with SCI admitted to the Spinal Cord Injury Centre of Western Denmark having sustained an injury to the spinal cord between 1 January 1997 and 1 January 2017. Age is presented as medians and interquartile ranges (IQR).
RESULTS
A total of 584 (women = 122; men = 462) traumatic patients with SCI with a median age of 42.9 years (26.4-58.3 years) were identified of whom 390 underwent surgery (SG) and 55 were treated conservatively forming a conservative group (CG). The acute treatment regime was unknown in 139 patients with SCI. Patients in the CG were significantly older (median 63.6 years (IQR: 39.1-71.5) than patients in the SG (median 52.8 years (IQR: 37.2-67.2), p = 0.02). The relative risk (RR) of fractures was higher in the SG (RR = 2.74 (1.91-3.95), p less than 0.0001). The initial American Spinal Injury Association Impairment Scale (AIS) grades (A, B, C and D) differed significantly (Kruskal-Wallis test, p less than 0.02) with a higher frequency of AIS Din the CG. Fewer persons with a cervical than with a non-cervical level of injury underwent spinal surgery (RR = 0.65 (0.54-0.77), p less than 0.0004).
CONCLUSIONS
In a Danish population of patients with traumatic SCI, we observed a preponderance for surgical treatment among a) younger patients, b) patients with vertebral fractures, and c) more severe SCI cases.
FUNDING
This study received no external funding.
TRIAL REGISTRATION
The study was conducted in accordance with the Helsinki II Declaration. Data were obtained with permission from the Danish Data Protection Agency (record number 2012-41-0572).
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pubmed_244_655
|
pubmed_940_3873
|
Recent evidence indicates that free oxygen radicals, in particular hydroxyl radicals, may act as intracellular second messengers for the induction of IL-8, a potent chemoattractant and activator of neutrophil granulocytes. Here we report that peroxynitrite (ONOO-), formed by a reaction of nitric oxide (NO) with superoxide, mediates IL-8 gene expression and IL-8 production in LPS-stimulated human whole blood. The NO synthase inhibitors aminoguanidine and NG-nitro-L-arginine methyl ester (L-NAME) blocked IL-8 release by approximately 90% in response to LPS (1 microg/ml), but did not affect the production of IL-1beta or TNF-alpha. Both aminoguanidine and L-NAME blocked the induction of IL-8 mRNA by LPS. Authentic ONOO- (2.5-80 microM) augmented IL-8 mRNA expression and stimulated IL-8 release in a concentration-dependent manner, whereas the NO-releasing compounds, S-nitroso-N-acetyl-DL-penicillamine and sodium nitroprusside failed to induce cytokine production. Combination of the NO-generating chemicals with a superoxide-generating system (xanthine/xanthine oxidase) markedly increased IL-8 release. Enhanced ONOO- formation was detected in granulocytes, monocytes, lymphocytes, and plasma after challenge with LPS. Furthermore, pyrrolidine dithiocarbamate, an inhibitor of activation of nuclear factor-gammaB, markedly attenuated the induction of IL-8 mRNA expression and IL-8 release by either LPS or ONOO-. Our study identifies ONOO- as a novel signaling mechanism for IL-8 gene expression and suggests that inhibition of ONOO- formation or scavenging ONOO- may represent a novel therapeutic approach to inhibit IL-8 production that could lead to reduction of neutrophil accumulation and activation.
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pubmed_940_3873
|
pubmed_698_17807
|
The mRNA's cap-binding protein eukaryotic translation initiation factor (eIF)4E is a major target for the regulation of translation initiation. eIF4E activity is controlled by a family of translation inhibitors, the eIF4E-binding proteins (4E-BPs). We have previously shown that a rapid dissociation of 4E-BP from eIF4E is related with the dramatic rise in protein synthesis that occurs following sea urchin fertilization. Here, we demonstrate that 4E-BP is destroyed shortly following fertilization and that 4E-BP degradation is sensitive to rapamycin, suggesting that proteolysis could be a novel means of regulating 4E-BP function. We also show that eIF4E/4E-BP dissociation following fertilization is sensitive to rapamycin. Furthermore, while rapamycin modestly affects global translation rates, the drug strongly inhibits cyclin B de novo synthesis and, consequently, precludes the completion of the first mitotic cleavage. These results demonstrate that, following sea urchin fertilization, cyclin B translation, and thus the onset of mitosis, are regulated by a rapamycin-sensitive pathway. These processes are effected at least in part through eIF4E/4E-BP complex dissociation and 4E-BP degradation.
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10.1016/s0012-1606(02)00099-4
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pubmed_272_15900
|
Birbeck granules are unusual rod-shaped structures specific to epidermal Langerhans cells, whose origin and function remain undetermined. We investigated the intracellular location and fate of Langerin, a protein implicated in Birbeck granule biogenesis, in human epidermal Langerhans cells. In the steady state, Langerin is predominantly found in the endosomal recycling compartment and in Birbeck granules. Langerin internalizes by classical receptor-mediated endocytosis and the first Birbeck granules accessible to endocytosed Langerin are those connected to recycling endosomes in the pericentriolar area, where Langerin accumulates. Drug-induced inhibition of endocytosis results in the appearance of abundant open-ended Birbeck granule-like structures appended to the plasma membrane, whereas inhibition of recycling induces Birbeck granules to merge with a tubular endosomal network. In mature Langerhans cells, Langerin traffic is abolished and the loss of internal Langerin is associated with a concomitant depletion of Birbeck granules. Our results demonstrate an exchange of Langerin between early endosomal compartments and the plasma membrane, with dynamic retention in the endosomal recycling compartment. They show that Birbeck granules are not endocytotic structures, rather they are subdomains of the endosomal recycling compartment that form where Langerin accumulates. Finally, our results implicate ADP-ribosylation factor proteins in Langerin trafficking and the exchange between Birbeck granules and other endosomal membranes.
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10.1091/mbc.01-06-0300
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pubmed_1057_10123
|
This study was conducted to identify genes that are differentially expressed in paracancerous tissue and to determine the potential predictive value of selected gene panel. Gene transcriptome data of bladder tissue was downloaded from UCSC Xena browser and NCBI GEO repository, including GTEx (the Genotype-Tissue Expression project) data, TCGA (The Cancer Genome Atlas) data, and GEO (Gene Expression Omnibus) data. Differentially Expressed Genes (DEGs) analysis was performed to identify tumor-DEGs candidate genes, using the intersection of tumor-paracancerous DEGs genes and paracancerous-normal DEGs genes. The survival-related genes were screened by Kaplan-Meier (KM) survival analysis and univariable Cox regression with the cutoff criteria of KM < 0.05 and cox p-value < 0.05. The risk model was developed using Lasso regression. The clinical data were analyzed by univariate and multivariate Cox regression analysis. Gene Ontology (GO) and KEGG enrichment analysis were performed in the DEGs genes between the high-risk and low-risk subgroups. We identified six survival-related genes, EMP1, TPM1, NRP2, FGFR1, CAVIN1, and LATS2, found in the DEG analyses of both, tumor-paracancerous and paracancerous-normal differentially expressed data sets. Then, the patients were classified into two clusters, which can be distinguished by specific clinical characteristics. A three-gene risk prediction model (EMP1, FGFR1, and CAVIN1) was constructed in patients within cluster 1. The model was applied to categorize cluster 1 patients into high-risk and low-risk subgroups. The prognostic risk score was considered as an independent prognostic factor. The six identified survival-related genes can be used in molecular characterization of a specific subtype of bladder cancer. This subtype had distinct clinical features of T (topography), N (lymph node), stage, grade, and survival status, compared to the other subtype of bladder cancer. Among the six identified survival-related genes, three-genes, EMP1, FGFR1, and CAVIN1, were identified as potential independent prognostic markers for the specific bladder cancer subtype with clinical features described.
|
10.1038/s41420-020-00295-x
|
pubmed_613_22067
|
We develop and analyze a scheme to achieve both spatial and energetic focusing of an ensemble of neutral particles which is based on an oscillating billiard with frictional forces. The interplay of two competing mechanisms, acceleration due to collisions with the oscillating billiard walls and deceleration caused by friction, leads to the emergence of attractors in phase space. Their specific properties, i.e., spatial localization and energy spread, can be controlled and tuned by varying, e.g., the frequency of the time-dependent billiard.
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10.1103/PhysRevE.82.035204
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pubmed_1133_17866
|
In this paper, we address the generation of semantic labels describing the headgear accessories carried out by people in a scene under surveillance, only using depth information obtained from a Time-of-Flight (ToF) camera placed in an overhead position. We propose a new method for headgear accessories classification based on the design of a robust processing strategy that includes the estimation of a meaningful feature vector that provides the relevant information about the people's head and shoulder areas. This paper includes a detailed description of the proposed algorithmic approach, and the results obtained in tests with persons with and without headgear accessories, and with different types of hats and caps. In order to evaluate the proposal, a wide experimental validation has been carried out on a fully labeled database (that has been made available to the scientific community), including a broad variety of people and headgear accessories. For the validation, three different levels of detail have been defined, considering a different number of classes: the first level only includes two classes (hat/cap, and no hat/cap), the second one considers three classes (hat, cap and no hat/cap), and the last one includes the full class set with the five classes (no hat/cap, cap, small size hat, medium size hat, and large size hat). The achieved performance is satisfactory in every case: the average classification rates for the first level reaches 95.25%, for the second one is 92.34%, and for the full class set equals 84.60%. In addition, the online stage processing time is 5.75 ms per frame in a standard PC, thus allowing for real-time operation.
|
10.3390/s17081845
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pubmed_27_22039
|
Adenosine, produced from the decomposition of adenosine triphosphate, is believed to provide protective effects during ischemia. On the other hand, adenosine metabolites may serve as precursors for oxygen free radical formation. These substances have not been previously measured in intact vertebrate retina, where adenosine and its metabolites may play a role in the pathogenesis of ischemic injury. The small tissue mass of the retina, particularly in rats, renders these measurements challenging. Furthermore, accurate measurement of purine nucleosides requires immediate cessation of ongoing adenosine metabolism. Concentrations of adenosine and its purine nucleoside metabolites inosine, hypoxanthine, and xanthine in the retina of ketamine/xylazine-anesthetized rats were measured after in situ freezing using high-performance liquid chromatography. The retina was removed from the frozen eyes and analyzed. Quantitative measurements were made possible through the use of an internal standard. Ischemia was induced by ligation of the central retinal artery. Retinal purine nucleoside concentrations did not differ between the two eyes of the rat under control conditions, and there was no effect of placement of the ligating suture itself compared to completely unmanipulated eyes. Use of two different in situ freezing methods yielded comparable results. To evaluate the impact of a period of ischemia, one retina of each rat was ischemic for 30 min, and the other, non-ischemic. Our measurements were associated with a high degree of reproducibility and minimal variability, and significant changes in purine nucleoside concentrations were detectable in the retina after 30 min of ischemia. Our method may be used to assess the role of adenosine and its metabolites in the pathogenesis of ischemic neuronal injury, including in the retina.
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10.1016/0165-0270(96)00061-1
|
pubmed_987_5275
|
Background
The development of easy-to-perform diagnostic methods is highly important for detecting current coronavirus disease (COVID-19). This pilot study aimed at developing a lateral flow assay (LFA)-based test prototype to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus in saliva samples.
Methods
Mice were immunized using the recombinant receptor-binding domain (rRBD) of SARS-CoV-2 virus spike protein. The combinations of the obtained mouse anti-receptor-binding domain (RBD) polyclonal antibodies (PAbs) and several commercial antibodies directed against the SARS-CoV-2 spike protein were used for enzyme-linked immunosorbent assay (ELISA) to select antibody pairs for LFA. The antibody pairs were tested in a LFA format using saliva samples from individuals with early SARS-CoV-2 infection (n = 9). The diagnostic performance of the developed LFA was evaluated using saliva samples from hospitalized COVID-19 patients (n = 111); the median time from the onset of symptoms to sample collection was 10 days (0-24 days, interquartile range (IQR): 7-13). The reverse transcription-polymerase chain reaction (rRT-PCR) was used as a reference method.
Results
Based on ELISA and preliminary LFA results, a combination of mouse anti-RBD PAbs (capture antibody) and rabbit anti-spike PAbs (detection antibody) was chosen for clinical analysis of sample. When compared with rRT-PCR results, LFA exhibited 26.5% sensitivity, 58.1% specificity, 50.0% positive prediction value (PPV), 33.3% negative prediction value (NPV), and 38.7% diagnostic accuracy. However, there was a reasonable improvement in assay specificity (85.7%) and PPV (91.7%) when samples were stratified based on the sampling time.
Conclusion
The developed LFA assay demonstrated a potential of SARS-CoV-2 detection in saliva samples. Further technical assay improvements should be made to enhance diagnostic performance followed by a validation study in a larger cohort of both asymptomatic and symptomatic patients in the early stage of infection.
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10.48101/ujms.v127.8207
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pubmed_585_6232
|
OBJECTIVE
To test the developmental competence of oocytes in a nonhCG-triggered in vitro maturation (IVM) system when oocyte-cumulus complexes (OCC) are retrieved from antral follicles with a diameter of <6 mm.
DESIGN
Prospective cohort study.
SETTING
Tertiary university-based referral center.
PATIENT(S)
From January 2010 to September 2011, 121 patients with polycystic ovaries/polycystic ovary syndrome underwent 239 IVM cycles in total. In 58 of these cycles (44 patients), all antral follicles had a diameter of <6 mm on the day of oocyte retrieval.
INTERVENTION(S)
NonhCG-triggered IVM of oocytes, fresh or vitrified/warmed embryo transfer (ET).
MAIN OUTCOME MEASURE(S)
Oocyte diameter, maturation rate, fertilization rate, embryo development and morphology, implantation rate, clinical pregnancy rate, ongoing pregnancy rate.
RESULT(S)
Oocyte retrieval yielded 16.7 OCC/cycle, and 50.8% of oocytes completed IVM. The mean oocyte diameter increased from 108.8 ± 4.3 μm to 111.9 ± 4.1 μm after IVM. Mean fertilization rate was 63.7%, and 45.4% of 2-pronuclei oocytes developed into a morphologically good-quality embryo on day 3 after intracytoplasmic sperm injection. Fresh ET resulted in two ongoing pregnancies (2/37; 5.4%). Deferred vitrified-warmed ET led to an ongoing pregnancy rate of 34.6% (9/24). Three healthy babies were born and eight pregnancies were still ongoing.
CONCLUSION(S)
Oocytes retrieved from follicles with a diameter of <6 mm grow during a 40-hour IVM culture can acquire full competence in vitro, as illustrated by their development into healthy offspring. Endometrial quality appears to be a crucial determinant of pregnancy after nonhCG-triggered IVM.
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10.1016/j.fertnstert.2012.01.114
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pubmed_960_12040
|
Obesity is a growing public health concern, affecting an estimated 11% of children in Western society. The impact of obesity-related morbidity and mortality on society is significant, with both genetic and environmental factors contributing to its development. In most individuals, food intake and energy expenditure are tightly regulated by a feedback system comprising a number of hormonal and central nervous system pathways. Leptin released from adipocytes acts on hypothalamic neurons to release proopiomelanocortin (POMC), leading to a cascade of neuronal and hormonal events that inhibit feeding behavior. Specific gene mutations in the leptin/POMC pathways account for only 5% of all cases of obesity, and most cases of familial or idiopathic obesity are polygenic in origin. Although further research to identify specific genetic causes of obesity may lead to more tailored therapies, significant changes in societal and individual behavior are needed to stop the obesity epidemic from progressing.
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pubmed_960_12040
|
pubmed_256_15807
|
Preliminary random and mass blood surveys undertaken between 2000-0100 h in a tea garden of Upper Assam revealed more than 8 per cent positivity for microfilaria (mf) of Wuchereria bancrofti. The mf carriers were considerably high among males (73) as compared to females (48). Culex quinquefasciatus was incriminated as a vector with man hour density of 68.5 in human dwellings (indoors). The detection of mf in children who had never moved from the area and filaria larvae in vector mosquitoes collected from human dwellings indicate that indigenous transmission is going on in the garden and that filariasis has become a local health problem.
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pubmed_256_15807
|
pubmed_635_23366
|
We have sequenced 463 presenting cases of myeloma entered into the UK Myeloma XI study using whole exome sequencing. Here we identify mutations induced as a consequence of misdirected AID in the partner oncogenes of IGH translocations, which are activating and associated with impaired clinical outcome. An APOBEC mutational signature is seen in 3.8% of cases and is linked to the translocation-mediated deregulation of MAF and MAFB, a known poor prognostic factor. Patients with this signature have an increased mutational load and a poor prognosis. Loss of MAF or MAFB expression results in decreased APOBEC3B and APOBEC4 expression, indicating a transcriptional control mechanism. Kataegis, a further mutational pattern associated with APOBEC deregulation, is seen at the sites of the MYC translocation. The APOBEC mutational signature seen in myeloma is, therefore, associated with poor prognosis primary and secondary translocations and the molecular mechanisms involved in generating them.
|
10.1038/ncomms7997
|
pubmed_85_22496
|
BACKGROUND
Dual red imaging (DRI), a novel image-enhanced endoscopic technique, is expected to improve visibility of thin vessels, but no reports of the clinical use of DRI in colorectal endoscopic submucosal dissection (ESD) have been published. We aimed to compare the visibility of vessels, demarcation line between the submucosal and muscle layers after injection of hyaluronate sodium with minute indigo carmine, and fibrosis on DRI with that on white light imaging (WLI). We applied the principle of DRI to the image of the submucosal layer during colorectal ESD as a pilot study.
METHODS
A total of seven physicians compared 17 DRI images to the corresponding WLI images in colorectal ESD. The physicians compared the number of arteries identified on DRI with the actual number of arteries. The physicians rated the visibility of vessels, the demarcation line between the submucosal and muscle layers after injection of hyaluronate sodium with minute indigo carmine, and fibrosis. Inter-observer agreement was also examined using the kappa statistic.
RESULTS
Visibility of vessels and the demarcation line between the submucosal and muscle layers after injection of hyaluronate sodium with minute indigo carmine improved with the use of DRI compared with that using WLI. DRI can discriminate between arteries and veins clearly through the color of the vessels.
CONCLUSIONS
DRI improves the visibility of vessels, especially that of arteries, as they appear orange, and the demarcation line of the muscle layer. DRI may help to make colorectal ESD safer and faster.
|
10.1177/1756283X16645501
|
pubmed_963_18145
|
UNLABELLED
Over 100 pathogenic point mutations and 200 deletions, insertions, and rearrangements have been identified since the first mitochondrial DNA mutations were described in 1988. About 60% of the point mutations affect mitochondrial tRNAs, 35% affect polypeptide subunits of the respiratory chain, and 5% affect mitochondrial ribosomal RNAs. The clinical phenotypes of mitochondrial tRNA disease span the spectrum of all known oxidative phosphorylation disorders and include MELAS, MERRF, Leigh syndrome, PEO, deafness, diabetes, sideroblastic anemia, myoclonus, skeletal myopathy, cardiomyopathy, and renal tubular acidosis. Mutations in respiratory chain proteins encoded by mtDNA result in phenotypes ranging from exercise intolerance to blindness, ataxia, dystonia, dementia, and Leigh syndrome.
CONCLUSION
The primary disorders of oxidative phosphorylation are commonly associated with a delayed age of onset, organ selectivity, and an episodic, progressive course. Organ-specific, non-ATP related functions of mitochondria are discussed as important considerations in evaluating the pathogenesis of mitochondrial disease.
|
10.1007/pl00014407
|
pubmed_34_3581
|
BACKGROUND
A rare case of intradiploic epidermoid cyst of the occipital bone is described and recent literature, which emphasizes the radiological evaluation and surgical treatment of this lesion is reviewed.
CASE DESCRIPTION
A 56-year-old female patient complained of headache and occasional episodes of vertigo for one year. Computed tomographic scan and magnetic resonance imaging were performed. The patient underwent occipital right craniotomy followed by total removal of the cyst and its capsule.
RESULT
The postoperative course was uneventful and the patient was discharged 4 days later.
CONCLUSION
A review of the literature shows that intradiploic epidermoid cyst of the occipital bone is rare. Correct radiological assessment and complete excision of this lesion and its capsule provides complete recovery.
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10.1016/j.neuchi.2007.06.003
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pubmed_582_8542
|
Single nutrients are no solution to the problem of malnutrition. It is essential that food based dietary guidelines (FBDG) are developed and implemented to overcome the diet related diseases and promote health in the population. A multidisciplinary group was constituted to develop FBDGs in India. A manual with scientific details and an abridged version were prepared with 6 goals and 14 dietary guidelines covering all age groups to overcome the public health nutritional problems. The guidelines are based on dietary patterns and specific outcomes of health and disease. Dietary diversification has been suggested as the practical approach. Diets from locally available and culturally accepted foods in household measures have been suggested to ensure optimal health. For successful implementation of FBDGs, political/bureaucratic commitment are essential. It must become a tool in the developmental plans for food, nutrition, agriculture, rural, educational and biotechnology policies. Workshops and meetings were organized to sensitise the administrative set-up. The intersectoral nature of FBDG for implementation was highlighted. The department of women and child development, which is responsible for implementing the National Nutritional Policy, was recognized as nodal agency. Meetings were organised for secondary target audiences. The press was invited to participate in popularization of the FBDGs. Social marketing strategies were used to match the local dietary and cultural aspects. Interpersonal communication and professional societies were used for better dissemination. Industry and legislative bodies were requested to take active action in this regard. The FBDGs have to be implemented to achieve food and nutrition security and the Millennium Development Goals.
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pubmed_582_8542
|
pubmed_204_24142
|
A trace amount of interfacial water is required to initiate hydrosilation reactions of trifunctional organosilanes to form surface assemblies. In recent studies, we have learned that water also has a critical role in directing molecular placement on surfaces because water can react with silicon to provide oxygenated sites for surface binding. Consequently, the wettability nature of substrates influences the placement and density of organosilane films formed by vapor-phase reactions. Nanopatterning protocols were designed using vapor-phase organosilanes and colloidal lithography to compare the wettability differences of hydrophilic mica(0001) compared to relatively hydrophobic Si(100) as a strategy for tracking the location of water on surfaces. The competition between hydrophobic and hydrophilic domains for the adsorption and coalescence of water condensed from vapor can be mapped indirectly by mapping the organosilanes, which bind to water at the solid interface, using atomic force microscopy. Trifunctional octadecyltrichlorosilane (OTS) was used as a marker molecule to map out the areas of the surface where water was deposited. The effect of systematic changes in film thickness and surface coverage of OTS was evaluated at the vapor/solid interface by adding an incremental amount of water to sealed reaction vessels to wet the surface and assessing the outcome after reaction with vapor-phase trichlorosilane. Reactive molecular dynamics simulations of the silicon-water vapor interface combined with electronic structure calculations of oxygenated silicon clusters with methyltrichlorosilane provided insight of the mechanism for surface binding, toward understanding the nature of the interface and wettability factors, which influence the association and placement of silane molecules on surfaces.
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10.1063/5.0046210
|
pubmed_1053_15276
|
Rabbits of the Alicia strain have a mutation (ali) that segregates with the immunoglobulin heavy-chain (lgh) locus and has a cis effect upon the expression of heavy-chain variable-region (VH) genes encoding the a2 allotype. In heterozygous a1/ali or a3/ali rabbits, serum immunoglobulins are almost entirely the products of the normal a1 or a3 allele and only traces of a2 immunoglobulin are detectable. Adult homozygous ali/ali rabbits likewise have normal immunoglobulin levels resulting from increased production of a-negative immunoglobulins and some residual ability to produce the a2 allotype. By contrast, the majority of the immunoglobulins of wild-type a2 rabbits are a2-positive and only a small percentage are a-negative. Genomic DNAs from homozygous mutant and wild-type animals were indistinguishable by Southern analyses using a variety of restriction enzyme digests and lgh probes. However, when digests with infrequently cutting enzymes were analyzed by transverse alternating-field electrophoresis, the ali DNA fragments were 10-15 kilobases smaller than the wild type. These fragments hybridized to probes both for VH and for a region of DNA a few kilobases downstream of the VH genes nearest the joining region. We suggest that this relatively small deletion affects a segment containing 3' VH genes with important regulatory functions, the loss of which leads to the ali phenotype. These results, and the fact that the 3' VH genes rearrange early in B-cell development, indicate that the 3' end of the VH locus probably plays a key role in regulation of VH gene expression.
|
10.1073/pnas.87.14.5444
|
pubmed_409_16623
|
The spread of drug-resistant organisms and increased international travel makes malaria a disorder of ever-increasing importance. This report reviews those aspects of malaria of surgical relevance. The importance of the spleen in host defence against malaria and other infections makes splenic preservation desirable whenever possible after rupture of the spleen. Tropical splenomegaly is caused by an abnormal immune response to malaria and is best managed medically. Careful selection of blood donors is essential to prevent transfusion malaria, and routine antimalarial prophylaxis is indicated for blood recipients in many endemic areas. The risk of postoperative malaria may justify chemoprophylaxis in certain patients.
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10.1002/bjs.1800770905
|
pubmed_459_15424
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Two isolates of simian retrovirus related to the human immunodeficiency virus (HIV) were obtained from apparently healthy mandrills, Papio (Mandrillus) sphinx, in western equatorial Africa. This virus, designated SIVMND (simian immunodeficiency virus from mandrills), appeared morphologically similar to HIV by electron microscopy, showed Mg2+-dependent reverse transcriptase activity, and induced cytopathic effect in human CD4-positive cells. Western blotting (immunoblotting) analyses revealed that the gag and pol products of SIVMND showed cross-reactivity with those of known HIVs and SIVs. Molecular clones covering full-length viral DNA were obtained from closed circular extrachromosomal DNA of SIVMND-infected cells. By clone-on-clone hybridization with known retroviruses of the HIV and SIV groups, SIVMND showed similar cross-hybridization with HIV-1, HIV-2, SIVAGM (African green monkey-derived SIV), and SIVMAC (rhesus macaque-derived SIV) in the gag and pol regions only at low stringency but not at high stringency, a result indicating that SIVMND is a new member of the HIV-SIV group. The existence of distinct SIVs in different monkey species suggest that recent interspecies transfer of HIV-SIV is unlikely in nature.
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10.1128/JVI.62.11.4044-4050.1988
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