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pubmed_1084_18991
Homeoprotein transcription factors play fundamental roles in development, ranging from embryonic polarity to cell differentiation and migration. Research in recent years has underscored the physiological importance of homeoprotein intercellular transfer in eye field development, axon guidance and retino-tectal patterning, and visual cortex plasticity. Here, we have used the embryonic chick neural tube to investigate a possible role for homeoprotein Pax6 transfer in oligodendrocyte precursor cell (OPC) migration. We report the extracellular expression of Pax6 and the effects of gain and loss of extracellular Pax6 activity on OPCs. Open book cultures with recombinant Pax6 protein or Pax6 blocking antibodies, as well as in ovo gene transfer experiments involving expression of secreted Pax6 protein or secreted Pax6 antibodies, provide converging evidences that OPC migration is promoted by extracellular Pax6. The paracrine effect of Pax6 on OPC migration is thus a new example of direct non-cell autonomous homeoprotein activity.
10.1242/dev.066282
pubmed_399_16985
1. A phase I study of buspirone was conducted in 7 healthy male volunteers. 2. Diazepam was selected as the control drug and administered in equipotent doses to buspirone. Dosage was initiated at 2.5mg and doubled until a maximum dosage of 20mg was attained. Subsequently, 10mg was administered once a day for three consecutive days. 3. Clinico-pharmacologically both drugs produced sleepiness/drowsiness, but dizziness, light-headed feeling and feeling of drunkenness were marked only in the diazepam group. 4. No drug-related abnormalities were observed in clinical laboratory test values, endocrinological tests and ECG. 5. On the Uchida-Kraepelin test, no change with the control values was observed under buspirone but subjects administered diazepam exhibited marked deterioration during the latter half of the test. Moreover, in the tapping test, significant impairment was observed in the diazepam group whereas buspirone had no effect. 6. On the EEG some fast waves were observed with diazepam whereas buspirone exhibited slow waves.
10.1016/0278-5846(89)90010-9
pubmed_445_1812
The therapeutic and educational needs of 31 children who, after attending a private pre-school for the physically handicapped, were mainstrained in public schools are described in this paper. Their adjustment was followed for one to three years. Information was gathered through questionnaires and interviews with parents, children, and classroom teachers on how successful and to what extent the children had been mainstreamed, as well as what physical, academic, and social problems were encountered. Patterns and trends of relative educational abilities and disabilities of children with spina bifida and cerebral palsy are discussed in view of the literature and the problems encountered by this population. Questions that teachers frequently asked of health professionals who are experienced in dealing with the effects of handicapping conditions as well as a procedure for providing this information are also discussed. Successful mainstreaming depends on cooperative work and mutual advocacy among health professionals, parents, and educational personnel.
pubmed_445_1812
pubmed_408_10932
We use injection therapy under the following circumstances: 1. After groin ligation in all cases with LSV varices and associated veins in thigh and around the knee. 2. When veins remain after groin ligation +/- stripping. 3. All patients with below knee veins whether new or previously operated affecting LSV or SSV. 4. Dilated dermal telangiectasis. 5. In the management of some ulcers. Why do methods of treatment go wrong? 1. Incomplete documentation and out of date examination of the patient. 2. Failure to follow the correct technique of treatment. 3. Failure to recognize deep venous insufficiency or underestimating stasis complications. Our indications for investigating the deep veins before treatment are: 1. Persistent oedema of the leg. 2. Recent or recurrent phlebothrombosis.
pubmed_408_10932
pubmed_764_4379
To determine whether changes in density (rho) of infarct and noninfarct zones during healing and remodeling after myocardial infarction influence estimates of left ventricular mass and detection of temporal changes by imaging, we measured weights (g) and volumes (mL) of infarct, noninfarct, and mixed tissue in hearts removed 1 to 42 days after anterior infarction in three groups of dogs: nonreperfused infarction treated with placebo or captopril, or infarcts reperfused after 2 h. In vivo mass was calculated from in vivo diastolic myocardial volumes (echocardiograms) and an assumed density of 1.05 g/mL or actual values derived from tissue weights and volumes. Over the 42 days, actual density deviated more from the assumed value of 1.05 in infarct than noninfarct zones, and the overall density was higher for reperfused than nonreperfused ventricles (1.09 vs. 1.06 g/mL, p < 0.01). Correction for density improved the correlation between absolute in vivo and postmortem mass slightly but not the detection of relative changes in mass in control, captopril, or reperfusion groups. These findings suggest that (i) densities of infarct and noninfarct zones differ and change during healing, especially after reperfusion, and (ii) correction for density provides more accurate estimates of volume-derived mass in reperfused hearts.
pubmed_764_4379
pubmed_18_14337
PURPOSE/OBJECTIVES To describe adolescents' experiences of living with mothers with breast cancer. RESEARCH APPROACH Qualitative. SETTING Northeastern United States. PARTICIPANTS 11 adolescents aged 13-19 years whose mothers were diagnosed with breast cancer within a year prior to the study. METHODOLOGIC APPROACH With Van Manen's phenomenologic interpretive paradigm, multiple levels of analysis of transcribed semistructured interviews yielded common themes and a unique account and understanding of adolescents' lives when their mothers have breast cancer. MAIN RESEARCH VARIABLES Adolescent coping and maternal breast cancer. FINDINGS Five distinct themes were identified: life changed, turning to self, learning to be with my mother, needing to normalize, and speaking openly--the importance of communication. Study findings uncovered the powerful role mothers held in the adolescents' lives. CONCLUSIONS The depth of the feelings and conflicts expressed by the adolescent participants, who appeared to be coping with their mothers' breast cancer, emphasizes the need to explore coping responses used in adolescent adjustment to maternal breast cancer. Given that all the adolescents reported some level of anxiety and conflict in their lives, further research should address factors that underlie their coping mechanisms. INTERPRETATION Study findings and insights underscore the significance of the maternal-adolescent relationship. Healthcare professionals need to ask more directed questions and develop interviewing and counseling skills to support mothers through this difficult illness. Adolescent children require support and guidance in coping with their mothers' breast cancer journey.
10.1188/09.ONF.571-577
pubmed_550_461
This article presents qualitative results collected 6 months after implementation of a clinical information system in four nursing homes in the Midwestern USA. Researchers explored initial implementation strategies, discussed employee experiences and analyzed employee satisfaction. Transcript-based analysis and axial coding were completed to illustrate recurring phenomena. Common attributes were identified by two gerontological nurse experts and a researcher with human factors expertise. Common themes emerging from 22 focus groups and direct observation of more than 120 nursing home staff were perception and cognition, change, workable systems, competence, and connectedness. Implementation strategies associated with lower satisfaction were availability of equipment, training resources, and the presence of information technology professionals. Initial clinical information system implementation strategies and employee satisfaction could be enhanced by the inclusion of a system life cycle charter plan, emphasizing change management procedures, improving start-up projections, hiring adequately trained information technology staff, and providing a system support plan. Findings will be useful to administrators and policy makers who are contemplating implementation of a clinical information system.
10.1097/01.NCN.0000280589.28067.18
pubmed_700_14361
The presence of metallothionein (MT) was demonstrated in placentae from cadmium-exposed and control rats by an immunohistochemical technique, using peroxidase as label and the diaminobenzidine procedure for the staining reaction. The protein was found in different regions of the placenta, i.e. in trophoblastic labyrinth, in spongiotrophoblast and in visceral yolk sac. Cytophotometric analysis of the final reaction product revealed that the amount of MT was increased in the placental labyrinth of cadmium-exposed rats. Increases were found in both nuclei and cytoplasm of trophoblast cells in the labyrinth region. Possible roles of MT in the transport of zinc and in the carbohydrate metabolism are discussed.
10.1007/BF00508314
pubmed_1038_16699
Behavioral hyposensitivity to repeated apomorphine administration has been observed in fluctuating parkinsonian patients. To investigate whether a similar phenomenon occurs in patients never treated with levodopa, we studied the response to apomorphine in 20 de novo patients with Parkinson's disease. Six patients showed no or minimal improvement after apomorphine injections (maximal dose 3.5 mg). Fourteen patients responded and were then given up to four repeated subcutaneous injections of apomorphine [minimal effective dose (MED)]. The responses of de novo patients were compared with responses in 10 patients with motor fluctuations previously studied by the same protocol. There was no significant difference in latency and duration of motor responses after repeated apomorphine injections in de novo patients. MED was similar in de novo and fluctuating patients, but duration of improvement induced by each apomorphine bolus was longer in the de novo group. These results indicate that response duration to apomorphine is longer in previously untreated patients and that behavioral tolerance associated with pulsatile dopaminergic stimulation by apomorphine occurs mainly in patients with more advanced disease under chronic levodopa therapy.
10.1097/00002826-199202000-00002
pubmed_42_6252
A suppression subtraction cDNA library representing mRNAs expressed at a higher level in a benign breast tumour-derived cell line relative to the malignant MCF-7A cell line contained cDNAs corresponding to mRNAs for plasminogen activator inhibitor I, annexin VIII and the EF-hand protein S100A2. S100A2 protein has previously been shown to be expressed in normal human breast epithelium, but not in human breast carcinoma cell lines. Using a PCR-based assay and in situ hybridization on histological sections of human breast specimens, the mRNA for S100A2 was shown to be present in all benign breast lesions examined as well as in normal epithelium. S100A2 mRNA was detectable in 37% of specimens of carcinoma in situ, but in less than 15% of carcinoma specimens. The results suggest that the loss of S100A2 is associated with the development of malignant cells and is not associated with early tumour development.
10.1054/bjoc.2000.1488
pubmed_232_18323
In response to overwhelming evidence and the consequences of poor-quality reporting of randomized, controlled trials (RCTs), many medical journals and editorial groups have now endorsed the CONSORT (Consolidated Standards of Reporting Trials) statement, a 22-item checklist and flow diagram. Because CONSORT primarily aimed at improving the quality of reporting of efficacy, only 1 checklist item specifically addressed the reporting of safety. Considerable evidence suggests that reporting of harms-related data from RCTs also needs improvement. Members of the CONSORT Group, including journal editors and scientists, met in Montebello, Quebec, Canada, in May 2003 to address this problem. The result is the following document: the standard CONSORT checklist with 10 new recommendations about reporting harms-related issues, accompanying explanation, and examples to highlight specific aspects of proper reporting. We hope that this document, in conjunction with other CONSORT-related materials (http://www.consort-statement.org), will help authors improve their reporting of harms-related data from RCTs. Better reporting will help readers critically appraise and interpret trial results. Journals can support this goal by revising Instructions to Authors so that they refer authors to this document.
10.7326/0003-4819-141-10-200411160-00009
pubmed_1003_23982
OBJECTIVE The purpose of this study was to determine the clinical role of fetal pulse oximetry to reduce cesarean delivery for a nonreassuring fetal heart rate tracing. STUDY DESIGN Singletons > or =28 weeks were randomized to fetal pulse oximetry plus electronic fetal heart rate monitoring (monitoring + fetal pulse oximetry) or monitoring alone. RESULTS Overall, 360 women in labor were recruited: 150 cases with monitoring+fetal pulse oximetry and 177 cases with monitoring alone were analyzed. Most demographic, obstetric, and neonatal characteristics were similar. Specifically, the gestational age, cervical dilation, and station of the fetal head were not differential factors. In addition, cesarean delivery for nonreassuring fetal heart rate tracing was not different between the group with monitoring+fetal pulse oximetry (29%) and the group with monitoring alone (32%; relative risk, 0.95; 95% CI, 0.75, 1.22). Likewise, cesarean delivery for arrest disorder was similar between the group with monitoring+fetal pulse oximetry (22%) and the group with monitoring alone (23%; relative risk, 1.05; 95% CI, 0.79, 1.44). However, the decision-to-incision time was shorter for the group with monitoring+fetal pulse oximetry (17.8 +/- 8.2 min) than for the group with monitoring alone (27.7 +/- 13.9 min; P < .0001). CONCLUSION The use of fetal pulse oximetry with electronic fetal heart rate monitoring does not decrease the rate of cesarean delivery, although it does alter the decision-to-incision time.
10.1016/j.ajog.2004.12.047
pubmed_767_5779
Characterization of natural colloids is the key to understand pollutant fate and transport in the environment. The present study investigates the relationship between size and fluorescence properties of colloidal organic matter (COM) from five tributaries of Poyang Lake. Colloids were size-fractionated using cross-flow ultrafiltration and their fluorescence properties were measured by three-dimensional excitation-emission matrix fluorescence spectroscopy (3D-EEM). Parallel factor analysis (PARAFAC) and/or Self-organizing map (SOM) were applied to assess fluorescence properties as proxy indicators for the different size of colloids. PARAFAC analysis identified four fluorescence components including three humic-like components (C1-C3) and a protein-like component (C4). These four fluorescence components, and in particular the protein-like component, are primarily present in <1 kDa phase. For the colloidal fractions (1-10 kDa, 10-100 kDa, and 100 kDa-0.7 μm), the majority of fluorophores are associated with the smallest size fraction. SOM analysis demonstrated that relatively high fluorescence intensity and aromaticity occur primarily in <1 kDa phase, followed by 1-10 kDa colloids. Coupling PARAFAC and SOM facilitate the visualization and interpretation of the relationship between colloidal size and fluorescence properties with fewer input variables, shorter running time, higher reliability, and nondestructive results. Fluorescence indices analysis reveals that the smallest colloidal fraction (1-10 kDa) was dominated by higher humified and less autochthonous COM.
10.1016/j.scitotenv.2018.05.099
pubmed_531_7450
In multiple pregnancy, an intense supervision of the fetal condition is indicated during pregnancy and delivery. With the aid of a recently developed actocardiograph originally described by Maeda, it is possible to monitor the fetal heart rate (FHR) and fetal movements (FM) of twins simultaneously on one tracing by 2 external Doppler transducers. Additional methods (stimulation, real-time and Doppler ultrasound) were tested in combination with the equipment. In addition, FHR tracings of triplets were registered during delivery simultaneously with FM and contractions. First patterns of "twin behaviour" are described. It may be concluded that this way of recording is of definite practical and potential scientific value.
10.1055/s-2008-1026227
pubmed_670_12851
Parenteral interferon-gamma (IFN-gamma) activates murine macrophages to inhibit Trypanosoma cruzi multiplication and diminishes parasitemia and mortality in acute infection. To investigate the role of endogenous IFN-gamma in acute infection, monoclonal antibody to IFN-gamma was injected intraperitoneally into mice. The 6250 neutralizing units given 24 and 96 h after infection reproducibly increased mortality (P less than .05). Histology sections showed markedly more nests of T. cruzi in treated mice. BALB/c, Swiss Webster, C57Bl/6, and C3H/HEN mice were susceptible to the effects of anti-IFN-gamma. Peritoneal macrophages from mice 4 days after infection and a single dose of 6250 units of anti-IFN-gamma had significantly reduced ability to inhibit T. cruzi multiplication. Multiple doses of anti-IFN-gamma delayed but did not prevent macrophage activation. These results indicate the critical role of endogenous IFN-gamma for macrophage activation and host defense against acute T. cruzi infection in mice.
10.1093/infdis/163.4.912
pubmed_737_17846
OBJECT Sellar lesions with suprasellar extension may cause loss of visual acuity and visual field damage due to compression of the optic chiasm. Using intraoperative MR (iMR) imaging to detect symptomatic lesion remnants adjacent to the optic chiasm (that may be resected in the same procedure) may positively affect the functional outcome of patients with these lesions. The aim of this study was to evaluate the correlation between visual improvement and optic nerve decompression detected by iMR imaging in patients undergoing transsphenoidal resection of pituitary lesions. METHODS A total of 32 patients (23 men and 9 women) who underwent transsphenoidal resection of sellar lesions causing visual impairment were included in this study. Tumor volume ranged from 0.9 cm(3) to 55.7 cm(3) (mean 9.8 ± 11.7 cm(3)). Preoperative assessment showed visual field damage in 31 patients (97%) and loss of visual acuity in 28 patients (88%). The latency period between the appearance of symptoms and transsphenoidal decompression was 14.9 ± 19.5 weeks. RESULTS Intraoperative MR imaging was performed after the resection was believed to be complete, or if further tumor removal was not safely possible due to changed conditions in the surgical field. Complete resection was detected on these initial scans in 17 patients (53%). Partial resection was achieved in 9 patients (28%) and tumor debulking in 6 (19%). Additional resection was possible in 8 (53%) of these 15 patients. Four (50%) of these 8 cases had suprasellar remnants and the optic chiasm was subsequently decompressed. In 5 cases optimal decompression of the optic chiasm was not possible. On early follow-up within 1 month after surgery, overall improvement of visual field damage was observed in 27 patients (87%). In 23 patients (74%), the Goldmann perimetry demonstrated complete recovery. Improvement of visual acuity was noted in 24 patients (86%). Eighteen patients (64%) regained full visual acuity. Identification of a decompressed optic chiasm on iMR imaging was significantly correlated with visual field improvement (p = 0.0007; positive predictive value 0.96, 95% CI 0.81-0.99) and relief of visual acuity deficits (p = 0.0002; positive predictive value 0.96, 95% CI 0.79-0.99). Two patients needed transcranial procedures for symptomatic tumor remnants detected on iMR imaging. CONCLUSIONS Intraoperative MR imaging findings correlate with prognosis of visual deficits after transsphenoidal decompression of the anterior optic pathways. The use of iMR imaging may prevent revision surgery for unexpected symptomatic remnants.
10.3171/2011.4.JNS101568
pubmed_1032_14825
BACKGROUND Temple headaches are common, yet the anatomic etiology of headaches in this region is often confusing. One possible cause of temple headaches is dysfunction of the auriculotemporal nerve (ATN), a branch of the third division of the trigeminal nerve. However, the site of pain is often anterior to the described path of the ATN, and corresponds more closely to a portion of the path of a small branch of the second division of the trigeminal nerve called the zygomaticotemporal nerve (ZTN). OBJECTIVES We present the anatomic and clinical differences between these 2 nerves and describe treatment approaches. Diagnosis is made by physical examination of the temporal fossa and the temporomandibular joint, and injection of local anesthetic over the tenderest nerve. RESULTS In general, treatments of headaches that generated from the peripheral nerve attempt to neutralize the pain origin using surgical or interventional pain techniques to reduce nerve irritation and subsequently deactivate stimulated migraine centers. CONCLUSIONS Treatment of temporal nerve entrapment includes medications, nerve injections, dental appliances, cryoneuroablation, chemical neurolysis, neuromodulation, and surgical decompression. KEY WORDS Headache, migraine, trigeminal nerve, Frey's syndrome, zygomaticotemporal nerve, auriculotemporal nerve, temple pain, jaw pain, ear pain, tooth pain.
pubmed_1032_14825
pubmed_26_14840
A 4-year-old male child with hepatitis A virus (HAV) infection is presented. His disease course was complicated by the development of pseudotumor cerebri (PC), as evidenced by symptoms and signs of increased intracranial pressure in the presence of normal cerebrospinal fluid examination and cranial magnetic resonance scan. The neurological examination was normal with the exception of the right-sided sixth cranial nerve paresis. His neurological course was uncomplicated with spontaneous recovery within three days. To our knowledge, this is the first report in the English literature of PC complicating the course of HAV in a child.
10.1097/SMJ.0b013e318195a4b8
pubmed_1042_6927
Pseudo-occlusion (PO) of the cervical internal carotid artery (cICA) can be caused by distal ICA occlusion. We explored the clinical impact of PO after mechanical thrombectomy (MT). Patients who underwent MT to treat distal ICA occlusions between July 2012 and March 2018 were reviewed. A cICA-PO was defined as when single phase computed tomography angiography (CTA) revealed a gradual decline in contrast above the level of the carotid bulb. We investigated the relationship between a cICA-PO and outcome; we also explored the association between successful recanalization and outcome. Among 71 patients, 40 (56.3%) exhibited cICA-PO and more likely to experience poor outcomes (80.0% vs. 25.8%, P < 0.001), hemorrhagic transformation (32.5% vs. 9.6%, P = 0.01), and a lower rate of successful recanalization (65.0% vs. 90.3%, P = 0.014) than the non-PO group. In binary logistic regression, a cICA-PO was independently associated with a poor outcome (odds ratio, 4.278; 95% CI, 1.080-33.006; P = 0.045). In the cICA-PO group, all patients who failed recanalization (n = 15) experienced poor outcomes, as did 69.2% of patients in whom recanalization was successful (P = 0.018). cICA-POs are common and have worse outcomes than non-PO patients. Patients with cICA-POs are more likely to exhibit poor outcomes after MT, particularly when recanalization fails.
10.1038/s41598-020-59609-9
pubmed_242_22189
Subacute Sclerosing Panencephalitis (SSPE) in HIV-infected children is a scarcely reported entity with previous reports describing fulminant course. The impact of highly active antiretroviral therapy (HAART) in altering its course remains unknown. We describe a child with HIV infection, who developed measles at 5 months of age and later developed SSPE at 14 years of age, remaining stable at 7 month follow-up, while on HAART for WHO (World Health Organisation) stage IV disease. The dynamics of HIV-related immunosuppression has an impact on the clinical course of SSPE. Contrary to reported cases of fulminant progression, a classic presentation with slow progression can be expected in children on HAART. We reemphasize the recommendation of "early measles vaccination" to prevent measles infection and subsequent SSPE in these children with an increasingly good life expectancy in the era of HAART.
10.4103/0972-2327.144299
pubmed_663_7205
Stress is known to be one of the risk factors of stroke, but only a few experimental studies have examined the possible mechanisms by which prior stress may affect stroke outcome. In stroke patients, infections impede neurological recovery and increase morbidity as well as mortality. We previously reported that stress induces a bacterial translocation and that prior immobilization stress worsens experimental stroke outcome through mechanisms that involve inflammatory mediators such as release of proinflammatory cytokines and enzyme activation. We now investigate whether bacterial translocation from the intestinal flora of rats with stress before experimental ischemia is involved in stroke outcome. We used an experimental paradigm consisting of exposure of Fischer rats to repeated immobilization sessions before permanent middle cerebral artery occlusion (MCAO). The presence of bacteria and the levels and expression of different mediators involved in the bacterial translocation were analyzed. Our results indicate that stress before stroke is related to the presence of bacteria in different organs (mesenteric nodes, spleen, liver, and lung) after MCAO and increases inflammatory colonic parameters (such as cyclooxygenase-2, inducible nitric oxide synthase, and myeloperoxidase), but decreases colonic immunoglobulin A, and these results are correlated with colonic inflammation and bacterial translocation. Understanding the implication of bacterial translocation during stress-induced stroke worsening is of great potential clinical relevance, given the high incidence of infections after severe stroke and their main role in mortality and morbidity in stroke patients.
10.1152/ajpregu.90825.2008
pubmed_157_7885
The phytochemical investigation of the roots of Rhus trichocarpa led to this isolation of five new alkyl phloroglucinol derivatives, characterized as (Z)-15-hydroxy-1-(2,4,6-trihydroxyphenyl)-9-octadecen-1-one (named trichocarpol A, 1), (Z)-15-hydroxy-1-(2,6-dihydroxy-4-methoxyphenyl)-9-octadecen-1-one (named trichocarpol B, 2), (Z)-17-hydroxy-1-(2,4,6-trihydroxyphenyl)-9-octadecen-1-one (named trichocarpol C, 3), (Z)-18-hydroxy-1-(2,4,6-trihydroxyphenyl)-9-octadecen-1-one (named trichocarpol D, 4), and (9Z,12Z)-18-hydroxy-1-(2,4,6-trihydroxyphenyl)-9,12-octadecadien-1-one (named trichocarpol E, 5), together with a known compound, 4-(2,6-dihydroxy-4-methoxyphenyl)-4-oxobutanoic acid (6). In vitro cytotoxic activity of compounds 1-6 was evaluated in the human gastric adenocarcinoma AGS cell line and compounds 1-5 showed significant cytotoxicity. Our results indicate that R. trichocarpa, especially the alkyl phloroglucinol derivatives in it, is a good source of promising natural agents for the treatment of gastric cancer.
10.1055/s-0035-1568276
pubmed_559_8535
AIM Natriuretic peptide receptor A (NPR-A) is the main physiological receptor for atrial natriuretic peptide (ANP). Maximal activation of NPR-A guanylyl cyclase (GC) requires ANP binding and ATP interaction with a putative cytoplasmic site. This study investigates the regulatory effect of ATP on GC-coupled NPR-A activity in Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). METHODS Cyclic GMP production and competitive inhibition of [(125)I]ANP(1-28) binding were performed in solubilized glomerular and papillary renal membranes. RESULTS Here, we report that incubation of renal glomerular and papillary membranes with ATP induced a concentration-dependent increase in basal and ANP(1-28)-stimulated GC activity that was significantly greater in SHR than in age-matched WKY. ATPgammaS was more effective than ATP and induced a greater stimulation of cGMP production in SHR than in WKY. In contrast, in solubilized membranes ATP exerted an inhibitory role on basal and ANP(1-28)-induced GC activity, suggesting that an accessory protein is required for ATP-induced GC activation. ATP increases NPR-A affinity for ANP(1-28) and decreased B(max) in crude and solubilized membranes. Kinetic analysis of GC-coupled NPR-A revealed that ATP reduced the Km and increased the V(max), an effect that was greater in SHR. CONCLUSION Our observations indicate that ATP exerts a greater net effect on NPR-A in SHR than in WKY, which might explain the greater rate of cGMP production observed in SHR compared to WKY.
10.1111/j.1748-1716.2006.01628.x
pubmed_1091_755
We respond to seven criticisms made by Vermeij et al. () regarding Miller & Wiens (). Their criticisms generally reflect misunderstandings, unsupported speculations, and topics that were explicitly addressed in our paper.
10.1111/ele.12950
pubmed_453_7916
The role of two conserved amino acid residues in the thiamin diphosphate binding site of yeast transketolase has been analyzed by site-directed mutagenesis. Replacement of E162, which is part of a cluster of glutamic acid residues at the subunit interface, by alanine or glutamine results in mutant enzymes with most catalytic properties similar to wild-type enzyme. The two mutant enzymes show, however, significant increases in the K0.5 values for thiamin diphosphate in the absence of substrate and in the lag of the reaction progress curves. This suggests that the interaction of E162 with residue E418, and possibly E167, from the second subunit is important for formation and stabilization of the transketolase dimer. Replacement of the conserved residue D382, which is buried upon binding of thiamin diphosphate, by asparagine and alanine, results in mutant enzymes severely impaired in thiamin diphosphate binding and catalytic efficiency. The 25-80-fold increase in K0.5 for thiamin diphosphate suggests that D382 is involved in cofactor binding, probably by electrostatic compensation of the positive charge of the thiazolium ring and stabilization of a flexible loop at the active site. The decrease in catalytic activities in the D382 mutants indicates that this residue might also be important in subsequent steps in catalysis.
10.1111/j.1432-1033.1997.t01-1-00646.x
pubmed_918_23536
BACKGROUND There is little evidence on movement impairment of the abdominal and pelvic floor muscles (PFM) in women with pelvic organ prolapse (POP). OBJECTIVES The aim of this study was to determine the movement impairments and interactions between the PFM and abdominal muscles in POP. METHOD The PFM and abdominal muscles of 100 conveniently sampled South African women with POP were assessed by ultrasonography, electromyography (EMG), the PERFECT scale, Sahrmann scale and a Pressure Biofeedback Unit (PBU). A demographic questionnaire determined contextual factors (exercise and medical history) and Visual Faces Scale pain intensities. Data were analysed descriptively and with Spearman and Pearson correlation coefficients. RESULTS Participants (59 ± 9.31 years) were mostly unemployed (80%), physically inactive (85%), with comorbidities, heart or vascular disease, hypothyroidism and depression. The mean levator hiatus at rest (56.38 mm, standard deviation [SD] 9.95), thickness (5.1 mm, SD 1.41), amount of movement (4.28 mm, SD 6.84), strength (level 1.89, SD 1.13) and endurance (4.04 s, SD 3.32) of the PFM indicated dysfunction. Median values of zero were found for the Sahrmann scale (interquartile [IQ] range [0-1]) and PBU (IQ range [0-2]) and 10.95 µV for abdominal EMG (IQ range [7.9-17.8]). Pelvic floor muscle strength, endurance, movement and EMG activity correlation was fair (r > 0.4, p < 0.001), as was PFM strength, endurance and abdominal muscle function (r > 0.4, p < 0.05). CONCLUSION Movement impairment of local and global stability and mobility functions of PFM and abdominal muscles was present, as well as correlations between these functions. Addressing these impairments may affect the identified contextual factors (socio-economic, psychological and lifestyle factors) and the possible activity limitations and participation restrictions in patients with POP. Further research is needed to investigate these interactions. CLINICAL IMPLICATIONS The findings suggest that assessment and management of patients with POP might need to be based on a comprehensive neuro-musculoskeletal assessment and a holistic approach. Standardised protocols for patients with pelvic floor dysfunction (PFD) should therefore be used with caution. Randomised controlled trials should investigate patient-specific and holistic intervention approaches.
10.4102/sajp.v75i1.472
pubmed_125_8029
BACKGROUND Multiplex immunohistochemistry (mIHC) permits the labeling of six or more distinct cell types within a single histologic tissue section. The classification of each cell type requires detection of the unique colored chromogens localized to cells expressing biomarkers of interest. The most comprehensive and reproducible method to evaluate such slides is to employ digital pathology and image analysis pipelines to whole-slide images (WSIs). Our suite of deep learning tools quantitatively evaluates the expression of six biomarkers in mIHC WSIs. These methods address the current lack of readily available methods to evaluate more than four biomarkers and circumvent the need for specialized instrumentation to spectrally separate different colors. The use case application for our methods is a study that investigates tumor immune interactions in pancreatic ductal adenocarcinoma (PDAC) with a customized mIHC panel. METHODS Six different colored chromogens were utilized to label T-cells (CD3, CD4, CD8), B-cells (CD20), macrophages (CD16), and tumor cells (K17) in formalin-fixed paraffin-embedded (FFPE) PDAC tissue sections. We leveraged pathologist annotations to develop complementary deep learning-based methods: (1) ColorAE is a deep autoencoder which segments stained objects based on color; (2) U-Net is a convolutional neural network (CNN) trained to segment cells based on color, texture and shape; and ensemble methods that employ both ColorAE and U-Net, collectively referred to as (3) ColorAE:U-Net. We assessed the performance of our methods using: structural similarity and DICE score to evaluate segmentation results of ColorAE against traditional color deconvolution; F1 score, sensitivity, positive predictive value, and DICE score to evaluate the predictions from ColorAE, U-Net, and ColorAE:U-Net ensemble methods against pathologist-generated ground truth. We then used prediction results for spatial analysis (nearest neighbor). RESULTS We observed that (1) the performance of ColorAE is comparable to traditional color deconvolution for single-stain IHC images (note: traditional color deconvolution cannot be used for mIHC); (2) ColorAE and U-Net are complementary methods that detect 6 different classes of cells with comparable performance; (3) combinations of ColorAE and U-Net into ensemble methods outperform using either ColorAE and U-Net alone; and (4) ColorAE:U-Net ensemble methods can be employed for detailed analysis of the tumor microenvironment (TME). We developed a suite of scalable deep learning methods to analyze 6 distinctly labeled cell populations in mIHC WSIs. We evaluated our methods and found that they reliably detected and classified cells in the PDAC tumor microenvironment. We also present a use case, wherein we apply the ColorAE:U-Net ensemble method across 3 mIHC WSIs and use the predictions to quantify all stained cell populations and perform nearest neighbor spatial analysis. Thus, we provide proof of concept that these methods can be employed to quantitatively describe the spatial distribution immune cells within the tumor microenvironment. These complementary deep learning methods are readily deployable for use in clinical research studies.
10.1186/s13000-020-01003-0
pubmed_565_11596
BACKGROUND AND PURPOSE Monitoring of intraparenchymal brain tissue oxygen tension (P(br)O(2)) is an emerging tool in neurocritical care. The purpose of this study was to determine if there is a relationship between CT perfusion (CTP) imaging parameters and P(br)O(2). METHODS Nineteen patients underwent continuous P(br)O(2) monitoring with probes placed to target white matter in the cerebral hemisphere. Twenty-two CTP studies were performed at the level of the oxygen electrode, as identified on concurrent nonenhanced CT. CTP analysis software was used to measure mean transit time (MTT) and cerebral blood volume (CBV) and to derive cerebral blood flow (CBF) for a region of interest (ROI) surrounding the oxygen probe. For correlation, P(br)O(2) levels and other physiologic parameters were recorded at the time of CTP. RESULTS P(br)O(2) values at the time of CTP were 2.7-54.4 mm Hg, MTT was 1.86-5.79 seconds, CBV was 1.18-8.76 mL/100 g, and CBF was 15.2-149.2 mL/100 g/min. MTT but not CBV or CBF was correlated with P(br)O(2) (r = -0.50, P = .017). MTT, CBV, or CBF were not correlated with other physiologic parameters, including mean arterial pressure, cerebral perfusion pressure, intracranial pressure, and fraction of inspired oxygen. On multivariable analysis, only P(br)O(2) was independently associated with MTT. CONCLUSION CTP assessment of ROI surrounding an oxygen probe in the intraparenchymal brain tissue is feasible and showed a significant correlation between P(br)O(2) and MTT. Further studies are warranted to determine the role of CTP in assessing acute brain injury and whether it can be used to prospectively identify brain regions at risk for tissue hypoxia that should be targeted for advanced neuromonitoring.
pubmed_565_11596
pubmed_282_16134
Selective accessibility mechanisms indicate that anchoring effects are results of selective retrieval of working memory. Neuroimaging studies have revealed that the right dorsolateral prefrontal cortex (DLPFC) is closely related to memory retrieval and performance. However, no research has investigated the effect of changing the cortical excitability in right DLPFC on anchoring effects. Transcranial direct current stimulation (tDCS) can modulate the excitability of the human cerebral cortex, while anodal and cathodal tDCS are postulated to increase or decrease cortical activity, respectively. In this study, we used tDCS to investigate whether effects of increased or decreased right DLPFC excitability influence anchoring effects in willingness to pay (WTP) experiments. Ninety participants were first randomly assigned to receive either anodal, cathodal, or sham stimulation of 15 min, then they performed a valuation task regarding WTP. The results showed that anchoring effects were negatively related to activities of right DLPFC: the anodal stimulation diminished anchoring effects while the cathodal stimulation increased anchoring effects. These outcomes provide one of the first instances of neural evidence for the role of the right DLPFC in anchoring effects and support psychological explanations of the selective accessibility mechanisms and cognitive sets.
10.3389/fpsyg.2017.01079
pubmed_962_2406
Trefoil Factor 1 (TFF1), the first member of the trefoil factor family, is normally expressed in the stomach mucosa. Ectopic expression is also observed in various human pathological conditions, notably in numerous carcinomas and gastrointestinal acute inflammatory disorders. In vivo experimental data using TFF1-deficient mice highlight the pleiotropic functions of TFF1: (i) it is a gastric tumor suppressor gene involved in gastric ontogenesis and homeostasis; (ii) it protects gut mucosa from aggression; (iii) it participates in folding secreted proteins inside the endoplasmic reticulum. At the cellular level, it limits cell proliferation and apoptosis, and favors cell differentiation. Collectively, these data suggest that TFF1 may provide an alternative pharmacological tool for the prevention and treatment of human gastrointestinal diseases.
10.1007/s00018-005-5479-3
pubmed_730_17777
Short-term exposure to ozone at peak ambient levels induces neutrophil influx and impairs lung function in healthy humans. In order to investigate the mechanisms contributing to neutrophil recruitment and to examine the role of T-cells in the acute inflammatory response, we exposed 12 healthy humans to 0.2 parts per million (ppm) of ozone and filtered air on two separate occasions for 2 h with intermittent periods of rest and exercise (minute ventilation = 30 L x min(-1)). Fibreoptic bronchoscopy was performed 6 h after the end of exposures. Total protein, tryptase, histamine, myeloperoxidase, interleukin (IL)-8 and growth-related oncogene-alpha (Gro-alpha) were measured and total and differential cell counts were performed in bronchoalveolar lavage (BAL) fluid. Flow cytometry was performed on BAL cells to study total T-cells, T-cell receptors (alphabeta and gammadelta), T-cell subsets (CD4+ and CD8+ cells) and activated T-cell subsets (CD25+). Using immunohistochemistry, neutrophils, mast cells, total T-cell numbers, T-cell subsets, CD25+ T-cells and leukocyte endothelial adhesion molecules including P-selectin, E-selectin, intercellular adhesion molecule (ICAM)-1 and vascular adhesion molecule (VCAM)-1 were quantified in the bronchial biopsies. Paired samples were available from nine subjects. Following ozone exposure there was a threefold increase in the proportion of polymorphonuclear neutrophils (PMNs) (p=0.07) and epithelial cells (p=0.05) in BAL fluid. This was accompanied by increased concentrations of IL-8 (p=0.01), Gro-alpha (p=0.05) and total protein (p=0.058). A significant positive correlation was demonstrated between the two chemokines and proportion of PMNs in BAL fluid. After ozone exposure there was a significant decrease in the CD4/CD8 ratio (p=0.05) and the proportion of activated CD4+ (p=0.01) and CD8+ T-cells (p=0.04). However, no significant changes were demonstrable in any of the inflammatory markers studied in the biopsies. Short-term exposure of healthy humans to 0.2 ppm ozone induced a neutrophil influx in peripheral airways at 6 h post exposure, but no apparent inflammatory response in proximal airways. This response seems to be mediated at least in part by interleukin-8 and growth-related oncogene-alpha.
10.1183/09031936.98.11061294
pubmed_124_11148
A series of 28 patients presenting with benign intracranial hypertension is reported. The diagnosis was based on normal CT scanning appearances, including ventricular size, and it is stressed that no further neuroradiological investigations were required. Conservative treatment is shown to be effective in the majority of patients. It is, however, suggested that surgical intervention in the form of a shunting procedure (lumboperitoneal in our cases) might prove necessary, if vision remains in jeopardy.
pubmed_124_11148
pubmed_726_9339
Real-time quantitative reverse transcription-polymerase chain reaction (qPCR) is an efficient and accurate method to detect and compare patterns of gene expression. The reliability of qPCR is highly dependent on the selection of appropriate reference genes used for normalization. By analyzing 16 potential candidates of reference genes (GAPDH, Actb, 18 s, PGK1, Hprt, Tbp, Rpl5, B2M, Gusb, Ppia, UBC, Sdha, Eef1a1, H2afz, Tkt and Ldha) through geNorm, we identified Ppia, Tbp, Hprt and Eef1a1 as the most stable reference genes while UBC, B2M, Gusb as the least stable ones during the chondrocyte differentiation of ATDC5 cells. Considering the low expression of Eef1a1 and Tbp would cause divergent results for they failed to provide accurate normalization for RNA extraction and reverse transcription efficiency, we recommended the use of Ppia and Hprt as the most suitable genes to normalize qPCR. In addition, although GAPDH, Actb and 18 s were usually adopted in most of studies using ATDC5 cells, they were found unstable and then were not ideal reference genes for qPCR assay in ATDC5 cells chondrocyte differentiation. Also, we further confirmed that the Ppia and Hprt worked well during chondrocyte differentiation of mouse mesenchymal cells.
10.1371/journal.pone.0064786
pubmed_284_5717
Intact neurons in cultures of fetal rodent spinal cord explants show stimulation-dependent uptake of horseradish peroxidase (HRP) into many small vesicles and occasional tubules and multivesicular bodies (MVB) at presynaptic terminals. Presynaptic terminals were allowed to take up HRP during 1 h of strychnine-enhanced stimulation of synaptic transmitter release and then "chased" in tracer-free medium either with strychnine or with 10 mM Mg++ which depresses transmitter release. Tracer-containing vesicles are lost from terminals under both chase conditions; the loss is more rapid (4-8 h) with strychnine than with 10 mM Mg++ (8-16 h). There is a parallel decrease in the numbers of labeled MVB's at terminals. Loss of tracer with 10 mM Mg++ does not appear to be due to the membrane rearrangements (exocytosis coupled to endocytosis) that presumably lead to initial tracer uptake; terminals exposed to HRP and Mg++ for up to 16 h show little tracer uptake into vesicles. Nor is the decrease likely to the due to loss of HRP enzyme activity; HRP is very stable in solution. During the chases there is a striking accumulation of HRP in perikarya that is far more extensive in cultures initially exposed to tracer with strychnine than 10 mM Mg++ regardless of chase conditions. Much of the tracer ends up in large dense bodies. These findings suggest that synaptic vesicle membrane turnover involves retrograde axonal transport of membrane to neuronal perikarya for further processing, including lysosomal degradation. The more rapid (4-8 h) loss of tracer-containing vesicles with strychnine may reflect vesicle membrane reutilization for exocytosis.
10.1083/jcb.67.1.215
pubmed_576_16244
Over the past decade, the philosophy of total quality has appeared in all fields of industry in Japan and the USA. This philosophy is now present all over Europe as well, Italy included. In 1993 the Arcispedale Santa Maria Nuova of Reggio Emilia, a town in Northern Italy, began to apply the total quality management philosophy, thus embarking on a course of continuous quality improvement. The present article describes the main steps which led to an external accredited team granting the emergency department of this hospital a quality system certificate in 1997 according to the international quality system requirements UNI EN ISO 9002. The importance of this work lies in the fact than an industrial quality standardization system, whose requirements have little in common with a traditional view of medical practice, can nevertheless be applied to a public health care department.
10.1097/00063110-200003000-00012
pubmed_704_11709
The recent coronavirus disease 2019 (COVID-19) global pandemic has resulted in unprecedented job losses in the United States, disrupting health insurance coverage for millions of people. Several models have predicted large increases in Medicaid enrollment among those who have lost jobs, yet the number of Americans who have gained coverage since the pandemic began is unknown. We compiled Medicaid enrollment reports covering the period from March 1 through June 1, 2020, for twenty-six states. We found that in these twenty-six states, Medicaid covered more than 1.7 million additional Americans in roughly a three-month period. Relative changes in Medicaid enrollment differed significantly across states, although enrollment growth was not systemically related to job losses. Our results point to the important effects of state policy differences in the response to COVID-19.
10.1377/hlthaff.2020.00900
pubmed_596_18432
Recent studies have implicated anatomical differences in speech-relevant brain regions of adults who stutter (AWS) compared to normally fluent adults (NFA). The present study focused on the region of the corpus callosum (CC) which is involved in interhemispheric processing between the left and right cerebral hemispheres. Two-dimensional segmentation of area and voxel-based morphometry were used to evaluate the corpus callosum. Results revealed that the rostrum and anterior midbody of the CC were larger in AWS than NFA. In addition, the overall callosa area was larger in AWS than NFA. The group comparison of white matter volume showed a cluster of increased white matter volume predominantly encompassing the rostrum across the midline portion in AWS. These results potentially reflect anatomical changes associated with differences in the hemispheric distribution of language processes that have been reported previously in AWS.
10.1016/j.jcomdis.2011.03.001
pubmed_476_14433
This article reports experimental validation for spatiotemporal deconvolution methods and simple empirical formulas to correct pressure and beamwidth measurements for spatial averaging across a hydrophone sensitive element. The method was validated using linear and nonlinear beams transmitted by seven single-element spherically focusing transducers (2-10 MHz; F /#: 1-3) and measured with five hydrophones (sensitive element diameters dg : 85-1000 [Formula: see text]), resulting in 35 transducer/hydrophone combinations. Exponential functions, exp( -αx ), where x = dg /( λ1F /#) and λ1 is the fundamental wavelength, were used to model focal pressure ratios p'/p (where p' is the measured value subjected to spatial averaging and p is the true axial value that would be obtained with a hypothetical point hydrophone). Spatiotemporal deconvolution reduced α (followed by root mean squared difference between data and fit) from 0.29-0.30 (7%) to 0.01 (8%) (linear signals) and from 0.29-0.40 (8%) to 0.04 (14%) (nonlinear signals), indicating successful spatial averaging correction. Linear functions, Cx + 1, were used to model FWHM'/FWHM, where FWHM is full-width half-maximum. Spatiotemporal deconvolution reduced C from 9% (4%) to -0.6% (1%) (linear signals) and from 30% (10%) to 6% (5%) (nonlinear signals), indicating successful spatial averaging correction. Spatiotemporal deconvolution resulted in significant improvement in accuracy even when the hydrophone geometrical sensitive element diameter exceeded the beam FWHM. Responsible reporting of hydrophone-based pressure measurements should always acknowledge spatial averaging considerations.
10.1109/TUFFC.2022.3150179
pubmed_569_6601
A comprehensive summary of more than 450 estrogenic chemicals including estrogenic endocrine disruptors is provided here to understand the complex and profound impact of estrogen action. First, estrogenic chemicals are categorized by structure as well as their applications, usage and effects. Second, estrogenic signaling is examined by the molecular mechanism based on the receptors, signaling pathways, crosstalk/bypassing and autocrine/paracrine/homeostatic networks involved in the signaling. Third, evaluation of estrogen action is discussed by focusing on the technologies and protocols of the assays for assessing estrogenicity. Understanding the molecular mechanisms of estrogen action is important to assess the action of endocrine disruptors and will be used for risk management based on pathway-based toxicity testing.
pubmed_569_6601
pubmed_176_16711
Nurse recruitment and the retention of a high-quality workforce are challenging issues facing rural hospitals and health centers. The Bassett Healthcare Network has met these challenges by building a supportive framework to develop and support nurses at every level of their professional careers. The organization has partnered with local colleges to help staff nurses further their education. These and other partnership endeavors, such as the organization's clinical ladder and collaborative continuing nursing education opportunities, are helping Bassett sustain and grow the nursing workforce across 8 counties in rural upstate New York and develop stronger ties with academic partners.
10.1016/j.cnur.2010.10.010
pubmed_78_21108
The present study detected three single nucleotide polymorphisms (SNPs), BanISNP at the PLA2G4A locus, rs1648833 at the PLA2G4B locus, and rs1549637 at the PLA2G4C locus, to investigate a genetic association between the cytosolic PLA2 (cPLA2) genes and schizophrenia. A total of 240 Chinese parent-offspring trios of Han descent were recruited for the genetic analysis. The transmission disequilibrium test (TDT) showed allelic association for rs1549637 (chi(2) = 5.68, uncorrected P = 0.017), but not for BanISNP and rs1648833. The conditioning on genotype (COG) test revealed a disease association for the BanISNP-rs1648833 combination (chi(2) = 12.54, df = 3, P = 0.0057) and for the BanISNP-rs1549637 combination (chi(2) = 9.72, df = 2, P = 0.021), but the conditioning on allele (COA) test did not show such an association for the above two combinations. Neither the COA test nor the COG showed a disease association for the rs1648833-rs1549637 combination. In the combination of all three SNPs, the COG test, but not the COA test, showed a strong association (chi(2) = 22.93, df = 6, P = 0.0008). These findings suggest that these three cPLA2 genes may all be involved in contributing to the etiology of schizophrenia although their effect size appears to be relatively small.
10.1002/ajmg.b.30210
pubmed_135_16471
Diabetes mellitus and arterial hypertension are among the five risk factors that increase mortality in the world. Both are chronic, non-communicable diseases (NCDs), that have a pathophysiological association. Advanced glycation end products (AGEs), produced by the lack of glycemic control in diabetic patients, interact with their AGE receptors (AGER) resulting in increased arterial stiffness, inflammation and endothelial changes - which increases the risk of developing hypertension and other complications. We ran a systematic review in Pubmed, SciELO, Cochrane Library and Web of Science databases using keywords and Boolean operators to optimize the search, with the objective of assessing the mechanism of non-enzymatic glycation of proteins present in patients with diabetes and its correlation with the onset of hypertension, exposing all the endothelial and cellular damage caused by AGEs. We found 719 papers, of which 99 were read in full, and 26 met the eligibility criteria and were included in the present review. AGEs should be considered one of the main cardiometabolic risk factors. Reducing the AGE-AGER interaction will result in cardiovascular protection and increased life expectancy.
10.1590/2175-8239-JBN-2022-0006en
pubmed_498_2672
Due to the inconsistent fluctuation of blood supply for transfusion, much attention has been paid to the development of artificial blood using other animals. Although mini-pigs are candidate animals, contamination of mini-pig T cells in artificial blood may cause a major safety concern. Therefore, it is important to analyze the cross-reactivity of IL-7, the major survival factor for T lymphocytes, between human, mouse, and mini-pig. Thus, we compared the protein sequences of IL-7 and found that porcine IL-7 was evolutionarily different from human IL-7. We also observed that when porcine T cells were cultured with either human or mouse IL-7, these cells did not increase the survival or proliferation compared to negative controls. These results suggest that porcine T cells do not recognize human or mouse IL-7 as their survival factor.
10.4110/in.2021.21.e24
pubmed_744_17402
Many studies have shown that different risk or problem behaviors in adolescence are interrelated. Given the increased use of various substances among adolescents in the United States and in most European countries, the question emerges whether there are more substance use "specialists" or a progression of a general substance use pattern. If the latter is the case, the interrelatedness of the different substances should remain stable over time in a representative sample and among subgroups characterized by gender and language. Data from 4,146 15-year-olds in Switzerland surveyed in 1986, 1994 and 1998 were analyzed, using confirmatory factor analyses based on polychoric correlations. Smoking, drunkenness and cannabis use greatly increased over the 12-year period. However, in the different survey years, the factor structure did not differ for all 15-year-olds in general or for subgroups. This progression of a general pattern refers to an increased normalization of recreational substance use in general, not only of cannabis use. Favorable attitudes towards general substance use are a challenge to substance use prevention in adolescence, and reveal a need for more research on such a progression in other countries.
10.1159/000077700
pubmed_584_6576
PURPOSE We studied the sonographic appearance of the anterior liver surface using an ultrasound scanner equipped with a 7.5-MHz annular-array transducer to determine the accuracy of this imaging modality in monitoring the course of chronic liver diseases. METHODS We prospectively evaluated patterns of the liver surface in the sonograms of 77 consecutive patients with chronic liver diseases who had undergone sonographic examination with a 7.5-MHz annular-array transducer and a 3.75-MHz convex-array transducer over a 2-year period and compared these findings with those of laparoscopy (using previously described categories) and histopathology. RESULTS Histopathologically confirmed disease prevalences for inactive chronic hepatitis, active chronic hepatitis, liver cirrhosis, and others were 10% (8/77), 56% (43/77), 29% (22/77), and 5% (4/77), respectively. The sonographic appearance of the liver surface with the 3.75-MHz transducer was classified as either a regular or an irregular pattern. The regular pattern corresponded to 69% (34/50) of the cases in laparoscopic category 200 or 300 and the irregular pattern with 85% (23/27) of the cases in category 400 or 500. The sonographic appearance of the liver surface with the 7.5-MHz transducer was classified as regular, unevenly irregular, diffusely irregular, or nodular. These 4 patterns detected 75% (24/32), 78% (14/18), 52% (12/23), and 75% (3/4) of the cases of laparoscopic categories 200, 300, 400, and 500, respectively. In a comparison of the sonographic patterns of the liver surface with the differential histopathologic findings, the regular sonographic pattern corresponded to 88% (7/8) of the cases of inactive chronic hepatitis, the unevenly irregular pattern with 35% (15/43) of the cases of active chronic hepatitis, and the diffusely irregular and nodular patterns (considered as 1 group) with 68% (15/22) of the cases of liver cirrhosis. CONCLUSIONS Our results suggest that sonographic evaluation of the liver surface with a 7.5-MHz annular-array transducer using this classification provides detailed information on the evolution of chronic liver diseases that correlates with the laparoscopic and histopathologic findings and thus is a useful noninvasive method for monitoring the disease course to cirrhosis.
10.1002/jcu.10195
pubmed_444_3757
In traditional optical design, a starting point is selected and coefficients optimization is then performed using software. The process requires considerable time and the involvement of a human with design skills and experience. In this Letter, a fast automatic method for freeform imaging systems design is proposed. Using a plane system as the input, a freeform optical system with high image quality can be designed automatically at high speed. The method consists of system construction and system correction, combining the advantages of the direct design method and the methods based on aberration analysis. After system construction generates a system with fundamental optical parameters, system correction is an iterative process that alternates between image plane correction and surfaces correction to improve the image quality to a high level. Two examples required 5 min 56 s and 6 min 10 s to design freeform systems with near-diffraction-limit image quality.
10.1364/OL.398924
pubmed_321_23034
Neurodegenerative diseases and traumatic brain injuries (TBI) are among the main causes of cognitive dysfunction in humans. At a neuronal network level, they both extensively exhibit focal axonal swellings (FAS), which in turn, compromise the information encoded in spike trains and lead to potentially severe functional deficits. There are currently no satisfactory quantitative predictors of decline in memory-encoding neuronal networks based on the impact and statistics of FAS. Some of the challenges of this translational approach include our inability to access small scale injuries with non-invasive methods, the overall complexity of neuronal pathologies, and our limited knowledge of how networks process biological signals. The purpose of this computational study is three-fold: (i) to extend Hopfield's model for associative memory to account for the effects of FAS, (ii) to calibrate FAS parameters from biophysical observations of their statistical distribution and size, and (iii) to systematically evaluate deterioration rates for different memory-recall tasks as a function of FAS injury. We calculate deterioration rates for a face-recognition task to account for highly correlated memories and also for a discrimination task of random, uncorrelated memories with a size at the capacity limit of the Hopfield network. While it is expected that the performance of any injured network should decrease with injury, our results link, for the first time, the memory recall ability to observed FAS statistics. This allows for plausible estimates of cognitive decline for different stages of brain disorders within neuronal networks, bridging experimental observations following neurodegeneration and TBI with compromised memory recall. The work lends new insights to help close the gap between theory and experiment on how biological signals are processed in damaged, high-dimensional functional networks, and towards positing new diagnostic tools to measure cognitive deficits.
10.3389/fnins.2017.00623
pubmed_561_1039
Access to the intensive care unit (ICU) is often tortuous as there is a high incidence of bed closure due to staff shortage, a problem exacerbated by a high rate of turnover. It is proposed that the first step in addressing the problem is to explore the reasons why people leave, illuminating areas of policy and practice that would benefit from amendment. Given that the issues concerned are complex and contextual in nature, an open exploratory approach was adopted, whereby respondents were interviewed using open questions and given the freedom to shape their responses according to their perceptions of the problem. The transcripts of eleven interviews were analysed, with four themes emerging which represent the most dominant factors influencing the respondents' decision to leave. These included stresses related to the work; inadequate opportunity for professional development; recognition and respect of others and the implications of shift-work. It was concluded that there needs to be a greater awareness of the potential for nurses to become excessively stressed in the ICU environment; that a decentralized management style may help maintain motivation; that rostering systems need to retain flexibility; and that there is a requirement for greater incentives to pursue a career in intensive care.
10.1054/iccn.2001.1599
pubmed_1066_21079
AIMS Risk prediction models (RPMs) for coronary artery disease (CAD), using variables to calculate CAD risk, are potentially valuable tools in prevention strategies. However, their use in the clinical practice is limited by a lack of poor model description, external validation, and head-to-head comparisons. METHODS AND RESULTS CAD RPMs were identified through Tufts PACE CPM Registry and a systematic PubMed search. Every RPM was externally validated in the three cohorts (the UK Biobank, LifeLines, and PREVEND studies) for the primary endpoint myocardial infarction (MI) and secondary endpoint CAD, consisting of MI, percutaneous coronary intervention, and coronary artery bypass grafting. Model discrimination (C-index), calibration (intercept and regression slope), and accuracy (Brier score) were assessed and compared head-to-head between RPMs. Linear regression analysis was performed to evaluate predictive factors to estimate calibration ability of an RPM. Eleven articles containing 28 CAD RPMs were included. No single best-performing RPM could be identified across all cohorts and outcomes. Most RPMs yielded fair discrimination ability: mean C-index of RPMs was 0.706 ± 0.049, 0.778 ± 0.097, and 0.729 ± 0.074 (P < 0.01) for prediction of MI in UK Biobank, LifeLines, and PREVEND, respectively. Endpoint incidence in the original development cohorts was identified as a significant predictor for external validation performance. CONCLUSION Performance of CAD RPMs was comparable upon validation in three large cohorts, based on which no specific RPM can be recommended for predicting CAD risk.
10.1093/eurjpc/zwab095
pubmed_340_21253
Benzimidazole-based allosteric inhibitors of the hepatitis C virus (HCV) NS5B polymerase were diversified to a variety of topologically related scaffolds. Replacement of the polar benzimidazole core by lipophilic indoles led to inhibitors with improved potency in the cell-based subgenomic HCV replicon system. Transposing the indole scaffold into a previously described series of benzimidazole-tryptophan amides generated the most potent inhibitors of HCV RNA replication in cell culture reported to date in this series (EC(50) approximately 50 nM).
10.1016/j.bmcl.2006.07.074
pubmed_272_21251
If the assumption of normality is not satisfied, there is no simple solution to this problem for the one-sample t test. The present study proposes Hall's or Johnson's transformation in conjunction with the trimmed mean to deal with the problem. Computer simulation is carried out to evaluate the small-sample behaviour of the proposed methods in terms of Type I error rate and statistical power. The proposed methods are compared with the conventional Student t, Yuen's trimmed t, Johnson's transformation untrimmed t, and Hall's transformation untrimmed t statistics for one-sided and two-sided tests. The simulation results indicate that the proposed methods can control Type I error well in very extreme conditions and are more powerful than the conventional methods.
10.1348/000711001159537
pubmed_1081_11689
PURPOSE To evaluate the effect of addition of different concentrations of thymoquinone (TQ) on the flexural strength, elastic modulus, surface roughness, and hardness of PMMA denture base material. MATERIALS AND METHODS A total of 160 rectangular specimens were prepared from heat-polymerized acrylic resin, with dimensions of 65 × 10 × 2.5 mm3 for flexural strength testing and 10 × 20 × 3 mm3 for surface property testing. The specimens were divided into eight groups of 20 specimens: one control group without addition of TQ and seven test groups prepared by adding TQ to acrylic powder in concentrations of 0.5, 1, 1.5, 2, 2.5, 3, and 5 wt%. The polymer was added to the monomer before being mixed, packed, and processed using the conventional water bath method. A universal testing machine was used to measure flexural strength and elastic modulus. A profilometer and a Vickers hardness tester were used to measure surface roughness and hardness, respectively. One-way ANOVA and the Tukey-Kramer multiple-comparison test were used for statistical analysis, with statistical significance at p ≤ 0.05. RESULTS Addition of TQ to PMMA denture base material significantly decreased flexural strength and elastic modulus at high concentrations (p < 0.01), while no significant differences were observed at low concentrations (0.5%, 1% TQ) in comparison with the control group. At high TQ concentrations, surface roughness increased while hardness decreased (p < 0.0001), and no significant differences were observed at low concentrations (0.5%, 1% TQ) in comparison with the control group. The most favorable addition values were 0.5% and 1% TQ in all TQ groups. CONCLUSIONS Addition of TQ did not affect the flexural and surface properties of PMMA denture base material at low concentrations (0.5%, 1% TQ) and could be incorporated into PMMA denture base material as an antifungal agent.
10.1111/jopr.12967
pubmed_244_12757
Acute lymphoid leukemia (ALL) is a malignant proliferation of abnormal lymphoid precursors in the bone marrow. It is the most common acute leukemia in childhood, accounting for only 20% of acute leukemia in adults. The clinical presentation is heterogeneous including pallor, fatigue and weakness. Diagnosis is performed through myelogram, bone marrow biopsy and immunophenotyping. Chemotherapy and, in some cases, bone marrow transplantation (BMT) are used to treat the disease. However, the efficacy of treatment in adult patients is still below expected and therapeutic innovations have not increased disease-free survival. In addition, about 20% of patients have relapse, usually generalized, of the disease. This article aims to report the case of a patient previously treated for ALL B presenting localized medullar relapse or in situ leukemia.
10.14740/jh436w
pubmed_491_5609
AIMS/HYPOTHESIS Upon tissue injury, peripheral sensory neurons release nociceptive factors (e.g. substance P [SP]), which exert local and systemic actions including the recruitment of bone marrow (BM)-derived haematopoietic stem and progenitor cells (HSPCs) endowed with paracrine pro-angiogenic properties. We herein explore whether diabetic neuropathy interferes with these phenomena. METHODS We first investigated the presence of sensory neuropathy in the BM of patients with type 2 diabetes by immunohistochemistry and morphometry analyses of nerve size and density and assessment of SP release by ELISA. We next analysed the association of sensory neuropathy with altered HSPC release under ischaemia or following direct stimulation with granulocyte colony-stimulating factor (G-CSF). BM and circulating HSPCs expressing the neurokinin 1 receptor (NK1R), which is the main SP receptor, were measured by flow cytometry. We finally assessed whether an altered modulation of SP secretion interferes with the mobilisation and homing of NK1R-HSPCs in a mouse model of type 2 diabetes after limb ischaemia (LI). RESULTS Nociceptive fibres were reduced in the BM of patients and mice with type 2 diabetes. Patients with neuropathy showed a remarkable reduction in NK1R-HSPC mobilisation under ischaemia or upon G-CSF stimulation. Following LI, diabetic mice manifested an altered SP gradient between BM, peripheral blood and limb muscles, accompanied by a depressed recruitment of NK1R-HSPCs to the ischaemic site. CONCLUSIONS/INTERPRETATION Sensory neuropathy translates into defective liberation and homing of reparative HSPCs. Nociceptors may represent a new target for treatment of diabetic complications.
10.1007/s00125-015-3735-0
pubmed_217_20715
OBJECTIVES Children come in contact with athletic fields on a daily basis. How these fields are maintained may have an impact on children's potential exposure to pesticides and associated health effects. DESIGN AND SAMPLE This is a cross-sectional, descriptive study that utilized a survey to assess playing field maintenance practices regarding the use of pesticides. Athletic fields (N = 101) in Maryland were stratified by population density and randomly selected. MEASURES A survey was administered to field managers (n = 33) to assess maintenance practices, including the use of pesticides. Analysis included descriptive statistics and generalized estimating equations. RESULTS Managers of 66 fields (65.3%) reported applying pesticides, mainly herbicides (57.4%). Managers of urban and suburban fields were less likely to apply pesticides than managers of rural fields. Combined cultivation practice was also a significant predictor of increased pesticide use. CONCLUSIONS The use of pesticides on athletic fields presents many possible health hazards. Results indicate that there is a significant risk of exposure to pesticide for children engaged in sports activities. Given that children are also often concurrently exposed to pesticides as food residues and from home pest management, we need to examine opportunities to reduce their exposures. Both policy and practice questions are raised.
10.1111/j.1525-1446.2012.01016.x
pubmed_963_2440
The case of a male infant is reported who had club foot on the right side and pes adductus on the left side in combination with acrofacial dysostosis; he also demonstrated preaxial anomalies of the upper limbs indicative of Nager syndrome. In addition, an unusual aberrant muscle was discovered during surgical correction of the right club foot.
10.1007/s004020000167
pubmed_986_11818
A randomized double blind placebo controlled study of the efficacy, duration and safety of epidural morphine for the management of pain after Cesarean section is reported. Three similar groups of patients received either 0, 4 mg or 8 mg of morphine sulphate in 10 ml of normal saline through an epidural catheter at the completion of the operation. Compared to the saline controls, both the 4 mg and 8 mg epidural morphine groups had significant pain relief as judged by an analogue pain scale (p less than 0.001), the time to the first administration of narcotic analgesics (p less than 0.001) and the amount of supplemental analgesic required in the first 36 hours after operation (p less than 0.001). The side effects occurred in a dose-dependent fashion. Two patients who received epidural morphine 8 mg plus additional narcotic or antihistamine had reduced respiratory rates but were easily rousable. Our experience suggests that the epidural administration of morphine 4 mg may be a safe and reliable method of obtaining prolonged analgesia following Caesarean section.
10.1007/BF03007526
pubmed_315_223
Nonconvulsive seizures (NCSs) after traumatic and ischemic brain injury are often refractory to antiepileptic drug therapy and are associated with a decline in patient outcome. We recently characterized an in vivo rat model of focal brain ischemia-induced NCS and here sought to evaluate potential pharmacological treatments. Electroencephalographic activity was recorded continuously for 24 h in freely behaving rats subjected to permanent middle cerebral artery occlusion (MCAo). Rats were treated with an antiepileptic drug from one of seven different drug classes at ED(50) and 2x ED(50) doses (as reported in other rat seizure models), delivered as a single i.v. injection 20 min post-MCAo. Vehicle-treated rats (n = 9) had an 89% incidence of NCS with an average number of NCS of 8.6 +/- 1.9. The latency to onset of NCS was 32.5 +/- 3.4 min post-MCAo with an average duration of 49.1 +/- 8.2 s/event. The high doses of ethosuximide, gabapentin, fos-phenytoin, and valproate significantly reduced the incidence of NCS (11, 14, 14, and 38%, respectively), whereas midazolam, phenobarbital, and dextromethorphan had no significant effect at either dose. Across treatment groups, there was a low but significant correlation between the number of NCS events per animal and volume of brain infarction (r = 0.352). Antiepileptic drug therapy that prevented the occurrence of NCS also reduced mortality from 26 to 7%. Based on combined effects on NCS, infarction, neurological recovery, and mortality, ethosuximide and gabapentin were identified as having the best therapeutic profile.
10.1124/jpet.104.069146
pubmed_248_22750
BACKGROUND Congenital peripheral elephantiasiformic alterations are very rare in paediatric patients. In a patient with lymphangiectasia-lymphedema syndrome we demonstrate over a 8-year follow-up that not only cosmetic and social indications for surgical treatments but also internal care become important during the course. PATIENT We report on a boy with congenital lymphedemas of the extremities and the genital region, which were several times surgically treated. The patient became symptomatic firstly with tetanic cramps caused by malabsorption syndrome due to intestinal lymphangiectasia at the age of 6 years. Synopsis of clinical and laboratory findings and the patient's course are pointing to a mild Hennekam syndrome with still unknown aetiology. RESULTS The boy developed adequately with permanent oral substitution of electrolytes and vitamins, protein-rich diet, supplementation of medium-chain fatty acids and compressing bandages. Infusions of human albumin to correct persistent hypalbuminemia as well as cytostatic treatment with cyclophosphamide as a formal trial were ineffective and are not advisable, therefore.
10.1055/s-2004-832486
pubmed_849_23169
BACKGROUND Cruciferous plants synthesize a large variety of tryptophan-derived phytoalexins in response to pathogen infection, UV irradiation, or high dosages of heavy metals. The major phytoalexins of Eutrema salsugineum (Thellungiella salsuginea), which has recently been established as an extremophile model plant, are probably derivatives of indole glucosinolates, in contrast to Arabidopsis, which synthesizes characteristic camalexin from the glucosinolate precursor indole-3-acetaldoxime. RESULTS The transcriptional response of E. salsugineum to UV irradiation and AgNO3 was monitored by RNAseq and microarray analysis. Most transcripts (respectively 70% and 78%) were significantly differentially regulated and a large overlap between the two treatments was observed (54% of total). While core genes of the biosynthesis of aliphatic glucosinolates were repressed, tryptophan and indole glucosinolate biosynthetic genes, as well as defence-related WRKY transcription factors, were consistently upregulated. The putative Eutrema WRKY33 ortholog was functionally tested and shown to complement camalexin deficiency in Atwrky33 mutant. CONCLUSIONS In E. salsugineum, UV irradiation or heavy metal application resulted in substantial transcriptional reprogramming. Consistently induced genes of indole glucosinolate biosynthesis and modification will serve as candidate genes for the biosynthesis of Eutrema-specific phytoalexins.
10.1186/s12870-015-0506-5
pubmed_322_6358
Octamer-binding transcription factor 4 (OCT4) regulates the pluripotency of stem cells and also plays important roles in granulosa cells growth, which is regulated by follicle-stimulating hormone (FSH). Thyroid hormone (TH) is important for the development and maturation of follicles and the maintenance of various endocrine functions. Although 3,5,3'-triiodothyronine (T3) enhances the effects of FSH on the regulation of the growth of granulosa cells and development of follicles, it is unclear whether and, if so, how TH combines with FSH to regulate OCT4 expression in granulosa cells during the preantral to early antral transition stage. Our results showed that T3 enhanced FSH-induced OCT4 expression. However, T3/FSH-induced cellular growth was reduced by OCT4 small interfering RNA. OCT4 knockdown significantly increased the number of apoptotic cell. Moreover, T3 combined with FSH to increase estrogen receptor β (ERβ) expression but did not significantly affect estrogen receptor α expression. ERβ knockdown dramatically decreased T3/FSH-induced OCT4 expression and cell development and increased cell apoptosis. The phosphoinositide 3-kinases/protein kinase B pathway was involved in hormones inducing OCT4 and ERβ expressions. Furthermore, the hormones regulating OCT4 and ERβ expressions were regulated by cytochrome P450 lanosterol 14a-demethylase (CYP51), a key enzyme in sterol and steroid biosynthesis. T3 and FSH cotreatment potentiated cellular development by upregulating OCT4 expression, which is mediated by CYP51 and ERβ. These regulatory processes are mediated by the phosphoinositide 3-kinase/protein kinase B signaling pathway. These findings suggest that OCT4 mediates the T3 and FSH-induced development of follicles.
10.1210/endocr/bqab183
pubmed_836_23871
CONTEXT Standard therapy for hot flashes has been hormone replacement with estradiol or progestational agents, but recent data suggest that antidepressants inhibiting serotonin reuptake may also be effective. OBJECTIVE To evaluate a selective serotonin reuptake inhibitor (paroxetine controlled release [CR]) in treating the vasomotor symptoms displayed by a general cross-section of menopausal women. DESIGN AND SETTING Randomized, double-blind, placebo-controlled, parallel group study conducted across 17 US sites, including urban, suburban, and rural clinics. PATIENTS A total of 165 menopausal women aged 18 years or older experiencing at least 2 to 3 daily hot flashes and must have discontinued any hormone replacement therapy for at least 6 weeks. Women were excluded if they had any signs of active cancer or were undergoing chemotherapy or radiation therapy. INTERVENTION After a 1-week placebo run-in phase, study participants were randomized to receive placebo or receive 12.5 mg/d or 25.0 mg/d of paroxetine CR (in a 1:1:1 ratio) for 6 weeks. MAIN OUTCOME MEASURES Mean change from baseline to week 6 in the daily hot flash composite score (frequency x severity). RESULTS Fifty-six participants were randomly assigned to receive placebo and 51 to receive 12.5 mg/d and 58 to receive 25.0 mg/d of paroxetine CR. The mean reductions in the hot flash frequency composite score from baseline to week 6 were statistically significantly greater for those receiving paroxetine CR than for those receiving placebo. By week 6, the mean daily hot flash frequency went from 7.1 to 3.8 (mean reduction, 3.3) for those in the 12.5-mg/d and from 6.4 to 3.2 (mean reduction, 3.2) for those in the 25-mg/d paroxetine CR groups and from 6.6 to 4.8 (mean reduction, 1.8) for those in the placebo group. Mean placebo-adjusted reduction in hot flash composite scores were -4.7 (95% confidence interval, - 8.1 to -1.3; P =.007) comparing 12.5-mg/d paroxetine CR with placebo; and -3.6 (95% confidence interval, -6.8 to -0.4; P =.03) comparing 25.0-mg/d paroxetine CR with placebo. This corresponded to median reductions of 62.2% for those in the 12.5-mg/d and 64.6% for those in the 25.0-mg/d paroxetine CR groups compared with 37.8% for those in the placebo group. CONCLUSION Paroxetine CR may be an effective and acceptable alternative to hormone replacement and other therapies in treating menopausal hot flash symptoms.
10.1001/jama.289.21.2827
pubmed_421_7935
BACKGROUND Dexmedetomidine is used as adjuvant in total intravenous anaesthesia (TIVA), but there have been few studies concerning its effect on intraoperative neurophysiological monitoring (IONM) during cranial surgery. Our aim was to study the effect of dexmedetomidine on IONM in patients undergoing brain stem and supratentorial cranial surgery. METHODS Two prospective, randomized, double-blind substudies were conducted. In substudy 1, during TIVA with an infusion of propofol and remifentanil, 10 patients received saline solution (SS) (PR group) and another 10 (PRD group) received dexmedetomidine (0.5 mcg/kg/h). Total dosage of propofol and remifentanil, intensity, latency and amplitude of motor-evoked potentials following transcranial electrical stimulation (tcMEPs) as well as somatosensory-evoked potentials (SSEP) were recorded at baseline, 15, 30, 45 minutes, and at the end of surgery. In order to identify differences in the same patient after dexmedetomidine administration, we designed substudy 2 with 20 new patients randomized to two groups. After 30 minutes with TIVA, 10 patients received dexmedetomidine (0.5 mcg/kg/h) and 10 patients SS. The same variables were recorded. RESULTS In substudy 1, propofol requirements were significantly lower (P = .004) and tcMEP intensity at the end of surgery was significantly higher in PRD group, but no statistically significant differences were observed for remifentanil requirements, SSEP and tcMEP latency or amplitude. In substudy 2, no differences in any of the variables were identified. CONCLUSIONS The administration of dexmedetomidine at a dosage of 0.5 mg/kg/h may reduce propofol requirements and adversely affect some neuromonitoring variables. However, it can be an alternative on IONM during cranial surgeries. REDEX EudraCT: 2014-000962-23.
10.1111/aas.13835
pubmed_1001_12046
Root resorption, an unwanted sequela of orthodontic treatment, has received much attention in the recent past. This is clearly evident from the enormous amount of literature published regarding this single iatrogenic issue. These research works should provide practitioners with great insight into the clinical, histologic, therapeutic, predictive, and genetic aspects as well as the molecular basis of the resorptive process. Yet the scientific community reading these reports is left with confounding questions requiring a proper organization of the published literature. This review is aimed at answering some critical issues concerning root resorption after orthodontic treatment. It also tries to update the theoretical information regarding the resorptive process, with an insight into recent human genetic and molecular-level research.
pubmed_1001_12046
pubmed_601_8954
Studies were conducted on the preparation, inactivation, safety, and immunogenicity of a prototype hepatitis A virus vaccine prepared from infected cell cultures. BS-C-1 cells maintained in medium 199 without serum were infected with the HM175 strain of hepatitis A virus and harvested after 21-28 days. The harvested virus preparation contained 6.8-7.4 (log 10) cell culture infectious doses/ml. After exposure to 1:4,000 formalin at 35 C, the infectivity titer decreased 10(6)-fold in 30 hr at an exponential rate, although virus was detected in 5.0-ml vaccine samples for up to three days. Three separate vaccine lots elicited antibody in all the guinea pigs given three doses. Owl monkeys given three doses of vaccine did not have any evidence of HAV infection but developed antibodies identifiable by radioimmunoassay and serum neutralization tests. After either oral or intravenous challenge with at least 10(6) monkey infectious doses of a virulent field strain of hepatitis A virus, none of the vaccinated monkeys shed virus in their feces or had elevated serum levels of alanine aminotransferase. The findings suggest that an effective inactivated whole virus hepatitis A vaccine can be prepared from cell culture.
10.1093/infdis/153.4.749
pubmed_880_24737
The title complex, [Dy(C(8)H(6)NO(4))(C(2)O(4))(H(2)O)](n), is a dysprosium coordination polymer with mixed anions and was obtained under hydrothermal conditions. In the structure, the oxalate and 5-amino-isophthalate ligands link the dysprosium ions, building up a two-dimensional metal-organic framework parallel to the (10) plane. These sheets are further connected through O-H⋯O, N-H⋯O and C-H⋯O hydrogen bonds, forming a three-dimensional supra-molecular structure.
10.1107/S1600536809019199
pubmed_632_9286
Current approaches of regenerative therapies constitute strategies for bone tissue reparation and engineering, especially in the context of genetical diseases with skeletal defects. Bone regeneration using electrospun nanofibers' implant has the following objectives: bone neoformation induction with rapid healing, reduced postoperative complications, and improvement of bone tissue quality. In vivo implantation of polycaprolactone (PCL) biomembrane functionalized with BMP-2/Ibuprofen in mouse maxillary defects was followed by bone neoformation kinetics evaluation using microcomputed tomography. Wild-Type (WT) and Tabby (Ta) mice were used to compare effects on a normal phenotype and on a mutant model of ectodermal dysplasia (ED). After 21 days, no effect on bone neoformation was observed in Ta treated lesion (4% neoformation compared to 13% in the control lesion). Between the 21st and the 30th days, the use of biomembrane functionalized with BMP-2/Ibuprofen in maxillary bone lesions allowed a significant increase in bone neoformation peaks (resp., +8% in mutant Ta and +13% in WT). Histological analyses revealed a neoformed bone with regular trabecular structure, areas of mineralized bone inside the membrane, and an improved neovascularization in the treated lesion with bifunctionalized membrane. In conclusion, PCL functionalized biomembrane promoted bone neoformation, this effect being modulated by the Ta bone phenotype responsible for an alteration of bone response.
10.1155/2018/7380389
pubmed_845_14358
In a candid interview with Neuron, Nikos K. Logothetis shares memories about his rich scientific past and argues about the importance of animal research and the role of science in society. He also talks about his new job and future plans as co-director of the International Center for Primate Brain Research in Shanghai.
10.1016/j.neuron.2020.05.033
pubmed_228_5449
Evaluation of limbs muscle function is one of the difficult tasks in forensic clinical medicine. Recently, there are more and more cases needed to be evaluated on the limbs muscle function in forensic clinical appraisal. Thus the assessment methods for muscle function have been concerned increasingly. This paper introduces the classification of muscle function and the type of muscle contraction, reviews the assessment methods for muscle function and their application value, such as manual muscle test, simple instrumental muscle test, isokinetic muscle test and electrophysiological test. It has also proposed to evaluate the muscle function with multiple methods comprehensively.
pubmed_228_5449
pubmed_691_7870
Proximal and distal the blindsack a villus and crypt prolongation connected with a decreasing absorption of octanoate could be pointed out. The structural changes are very likely a hyperplasia of the mucosa. Within the blindsack a hyperplasia in connection with an accelerated proliferation of cells and an almost three and a halffold enlargement of the surface of the villi could be found. Simultaneously, the mucosa was damaged. An artificial bile duct as well as a neomycin therapy caused a decrease of the structural and functional changes but did not prevent the mucosal hyperplasia. These results are explained with adaptive processes of the small intestinal mucosa in a sense of hyperregeneration alterations of sprue typus.
10.1002/food.19840280631
pubmed_458_8895
The native human antibody repertoire holds unexplored potential for the development of novel monoclonal antibody therapeutics. Current techniques that fuse immortal cells and primary B-lymphocytes are sub-optimal for the routine production of hybridomas that secrete human monoclonal antibodies. We have found that a murine cell line that ectopically expresses murine interleukin-6 (mIL-6) and human telomerase (hTERT) efficiently forms stable human antibody-secreting heterohybridomas through cell fusion with primary human B-lymphocytes. The hybrid cells maintain secretion of human antibodies derived from the primary B-lymphocytes through multiple rounds of cloning. Using splenic B-lymphocytes from a patient immunized with a Streptococcus pneumoniae capsular polysaccharide vaccine, we have succeeded in creating hybridomas that secrete human monoclonal antibodies specific for S. pneumoniae antigens. Using peripheral blood lymphocytes, we have similarly cloned a human antibody that binds a viral antigen. These experiments establish that SP2/0-derived cell lines ectopically expressing mIL-6 and hTERT will enable the rapid cloning of native human monoclonal antibodies.
10.1016/j.jim.2004.05.005
pubmed_763_23850
OBJECTIVE Celastrol has been established as a nuclear factor-κB (NF-κB) activation inhibitor; however, the exact mechanism behind this action is still unknown. Using text-mining technology, the authors predicted that interleukin-1 receptor-associated kinases (IRAKs) are potential celastrol targets, and hypothesized that targeting IRAKs might be one way that celastrol inhibits NF-κB. This is because IRAKs are key molecules for some crucial pathways to activate NF-κB (e.g., the interleukin-1 receptor (IL-1R)/Toll-like receptor (TLR) superfamily). METHODS The human hepatocellular cell line (HepG2) treated with palmitic acid (PA) was used as a model for stimulating TLR4/NF-κB activation, in order to observe the potential effects of celastrol in IRAK regulation and NF-κB inhibition. The transfection of small interfering RNA was used for down-regulating TLR4, IRAK1 and IRAK4, and the Western blot method was used to detect changes in the protein expressions. RESULTS The results showed that celastrol could effectively inhibit PA-caused TLR4-dependent NF-κB activation in the HepG2 cells; PA also activated IRAKs, which were inhibited by celastrol. Knocking down IRAKs abolished PA-caused NF-κB activation. CONCLUSION The results for the first time show that targeting IRAKs is one way in which celastrol inhibits NF-κB activation.
pubmed_763_23850
pubmed_856_3855
Active inflammatory bowel disease (IBD) often coincides with increases of Ruminococcus gnavus, a gut microbe found in nearly everyone. It was not known how, or if, this correlation contributed to disease. We investigated clinical isolates of R. gnavus to identify molecular mechanisms that would link R. gnavus to inflammation. Here, we show that only some isolates of R. gnavus produce a capsular polysaccharide that promotes a tolerogenic immune response, whereas isolates lacking functional capsule biosynthetic genes elicit robust proinflammatory responses in vitro. Germ-free mice colonized with an isolate of R. gnavus lacking a capsule show increased measures of gut inflammation compared to those colonized with an encapsulated isolate in vivo. These observations in the context of our earlier identification of an inflammatory cell-wall polysaccharide reveal how some strains of R. gnavus could drive the inflammatory responses that characterize IBD.
10.1073/pnas.2007595118
pubmed_64_2514
Different methods of measuring cavitation resistance in fern petioles lead to variable results, particularly with respect to the P50 metric. We hypothesised that the fern dictyostele structure affects air entry into the xylem, and therefore impacts the shape of the vulnerability curve. Our study examined this variation by comparing vulnerability curves constructed on petioles collected from evergreen and deciduous ferns in the field, with curves generated using the standard centrifuge, air-injection and bench-top dehydration methods. Additional experiments complemented the vulnerability curves to better understand how anatomy shapes estimates of cavitation resistance. Centrifugation and radial air injection generated acceptable vulnerability curves for the deciduous species, but overestimated drought resistance in the two evergreen ferns. In these hardy plants, axial air injection and bench-top dehydration produced results that most closely aligned with observations in nature. Additional experiments revealed that the dictyostele anatomy impedes air entry into the xylem during spinning and radial air injection. Each method produced acceptable vulnerability curves, depending on the species being tested. Therefore, we stress the importance of validating the curves with in situ measures of water potential and, if possible, hydraulic data to generate realistic results with any of the methods currently available.
10.1111/nph.17374
pubmed_558_16934
BACKGROUND We report our results for the systematic recording of all errors in a standard clinical laboratory over a 1-year period. METHODS Recording was performed using a commercial database program. All individuals in the laboratory were allowed to report errors. The testing processes were classified according to function, and errors were classified as pre-analytical, analytical, post-analytical, or service-related, and then further divided into descriptive subgroups. Samples were taken from hospital wards (38.6%), outpatient clinics (25.7%), general practitioners (29.4%), and other hospitals. RESULTS A total of 1189 errors were reported in 1151 reports during the first year, corresponding to an error rate of 1 error for every 142 patients, or 1 per 1223 tests. The majority of events were due to human errors (82.6%), and only a few (4.3%) were the result of technical errors. Most of the errors (81%) were pre-analytical. Of the remainder, 10% were analytical, 8% were post-analytical, and 1% was service-related. Nearly half of the errors (n=550) occurred with samples received from general practitioners or clinical hospital wards. Identification errors were relatively common when non-technicians collected blood samples. CONCLUSIONS Each clinical laboratory should record errors in a structured manner. A relation database is a useful tool for the recording and extraction of data, as the database can be structured to reflect the workflow at each individual laboratory.
10.1515/CCLM.2009.272
pubmed_888_13861
AIMS To determine the impact on nursing work-force supply of delaying retirement. BACKGROUND DATA The nursing workforce is aging, and the Baby Boomer generation is nearing retirement age. This potential loss of experienced nurses is likely to exacerbate current nursing shortages. METHODS An analysis of loss rates of nurses in New South Wales (Australia) is provided using 2 different retirement ages--58 and 65 years. Supply numbers were used and then "aged" to determine the impact of retirement on workforce numbers. The impact of potential retention strategies on the numbers who could be retained were determined if 100% of 50- to 55-year-old nurses was retained, 75% of those 56 to 60 years, and 50% of those 61 to 65 years. RESULTS By the year 2004, approximately 4139 nurses (registered and enrolled) will be lost through retirement at age 65 years. However, retirement at age 58 years sees 7328 lost by 2004. Potentially 2139 nurses in this age spectrum could be retained if strategies are focused on delaying retirement. CONCLUSIONS Delaying the retirement of nurses could provide a significant human resource, not only in terms of absolute numbers but more importantly, in terms of experience and expertise. However, retention of this portion of the workforce may require different strategies than for younger members of the workforce. The needs of this segment of the nursing workforce may require nurse administrators to consider different approaches to nursing work and work allocation.
10.1097/00005110-200406000-00009
pubmed_271_22841
OBJECTIVE Uremia represents a state where hyperhomocysteinemia is resistant to folate therapy, thus undermining intervention trials' efficacy. N-acetylcysteine (NAC), an antioxidant, in addition to folates (5-methyltetrahydrofolate, MTHF), was tested in a population of hemodialysis patients. DESIGN The study is an open, parallel, intervention study. SETTING Ambulatory chronic hemodialysis patients. SUBJECTS Clinically stable chronic hemodialysis patients, on hemodialysis since more than 3 months, undergoing a folate washout. Control group on standard therapy (n = 50). INTERVENTION One group was treated with intravenous MTHF (MTHF group, n = 48). A second group was represented by patients treated with MTHF, and, during the course of 10 hemodialysis sessions, NAC was administered intravenous (MTHF + NAC group, n = 47). MAIN OUTCOME MEASURE Plasma homocysteine measured before and after dialysis at the first and the last treatment. RESULTS At the end of the study, there was a significant decrease in predialysis plasma homocysteine levels in the MTHF group and MTHF + NAC group, compared with the control group, but no significant difference between the MTHF group and MTHF + NAC group. A significant decrease in postdialysis plasma homocysteine levels in MTHF + NAC group (10.27 ± 0.94 μmol/L, 95% confidence interval: 8.37-12.17) compared with the MTHF group (16.23 ± 0.83, 95% confidence interval: 14.55-17.90) was present. In the MTHF + NAC group, 64% of patients reached a postdialysis homocysteine level <12 μmol/L, compared with 19% in the MTHF group and 16% in the control group. CONCLUSIONS NAC therapy induces a significant additional decrease in homocysteine removal during dialysis. The advantage is limited to the time of administration.
10.1053/j.jrn.2011.10.007
pubmed_361_23917
The authors describe a case of well differentiated (grade I) chondrosarcoma in a 52-year-old male. The tumor originated in the posteromedial wall of the left petrous bone and extended into the posterior fossa and cervical spine. He showed impaired functions of the left VII to XII cranial nerves. Plain skull x-rays demonstrated erosion of the left petrous and occipital bones, with speckled calcifications. Computed tomography showed a huge mass of slightly high density with mushroom-like calcifications, which was poorly enhanced by contrast medium. Inversion recovery magnetic resonance imaging clearly defined the low-intensity lesion, while the long spin-echo image depicted the tumor as mixed-intensity. On electron microscopic examination, the tumor cells were rich in Golgi apparatus, endoplasmic reticulum, glycogen granules and mitochondria in the cytoplasm, and formed many vacuoles crossing the cell membrane. These vacuoles were suggested to play an important role in matrix formation. Thirty nine other reported cases of chondrosarcoma are reviewed, and the two reported posterior fossa chondrosarcomas are compared with that of ours.
10.2176/nmc.29.1030
pubmed_164_3962
Previous studies have demonstrated that the overexpression of Kif2a is involved in the progression, invasion and metastasis of squamous cell carcinoma of the oral tongue (SCCOT). Few studies have reported the correlation between Kif2a and apoptosis of tumor cells and which signaling pathways Kif2a is involved in remains unclear. The phosphatidylinositol‑3‑kinase (PI3K)/protein kinase B (Akt) pathway is frequently activated in many types of human cancer. The aim of the present study was to investigate the effects of downregulation of Kif2 expression on the P13K/Akt pathway in Tca8113 cells to determine whether silencing of Kif2 inhibits the P13K/Akt pathway, resulting in cell apoptosis. siRNA vector was constructed, western blot analysis was used to determine RNA interference and flow cytometry was used to determine promotion of Tca8113 cell apoptosis. The results revealed that silencing Kif2a induces apoptosis and decreases the mRNA and protein level of PI3K, Akt and B‑cell lymphoma 2 (Bcl‑2) in Tca8113 cells. The PI3K-specific agonist insulin‑like growth factor 1 (IGF‑1) eliminated the upregulation of apoptosis of Tca8113‑Kif2a cells by phosphorylation of Akt. The results suggest that silencing Kif2a induces tumor cell apoptosis, at least partially, through the PI3K/Akt signaling pathway.
10.3892/mmr.2013.1804
pubmed_197_10593
To study the efficiency of maintaining the reduced tissue environment via pre-treatment with natural antioxidant resveratrol in stem cell therapy, we pre-treated male Sprague-Dawley rats with resveratrol (2.5 mg/kg/day gavaged for 2 weeks). After occlusion of the left anterior descending coronary artery (LAD), adult cardiac stem cells stably expressing EGFP were injected into the border zone of the myocardium. One week after the LAD occlusion, the cardiac reduced environment was confirmed in resveratrol-treated rat hearts by the enhanced expression of nuclear factor-E2-related factor-2 (Nrf2) and redox effector factor-1 (Ref-1). In concert, cardiac functional parameters (left ventricular ejection fraction and fractional shortening) were significantly improved. The improvement of cardiac function was accompanied by the enhanced stem cell survival and proliferation as demonstrated by the expression of cell proliferation marker Ki67 and differentiation of stem cells towards the regeneration of the myocardium as demonstrated by the enhanced expression of EGFP 28 days after LAD occlusion in the resveratrol-treated hearts. Our results demonstrate that resveratrol maintained a reduced tissue environment by overexpressing Nrf2 and Ref-1 in rats resulting in an enhancement of the cardiac regeneration of the adult cardiac stem cells as demonstrated by increased cell survival and differentiation leading to cardiac function.
10.1111/j.1582-4934.2010.01140.x
pubmed_106_22020
Prevalence of sparganum in the frog (Rana nigromaculata) was surveyed in Dae-jeon city and in suburbs of the city, Chungnam Do. 39 (3.9 %) out of 1,011 frogs were infected with the worm, and the highest prevalence rate of sparganum was found the frogs from Shintanjin area(11.3 %). Infection rates of sparganum were observed due to the body weight and sex of frogs. The highest infection rate of frogs, the body weight of 50 gms or more, showed 30.3 per cent(female: 41.7 %, male: none), on the other hand, no worm was found in young frogs(less than 10 gms). Distribution of sparganum in the frogs was recorded and 82.6 % of worms were distributed in the femoral intermuscular connective tissues of the hind legs. Among those infected frogs, number of worm burden was one to five worms, and 53.3 per cent of frogs were infected by only one worm.
10.3347/kjp.1975.13.2.159
pubmed_1030_857
OBJECTIVE Several small-scale studies have suggested a biological link between obsessive-compulsive disorder (OCD) and Parkinson disease (PD). However, the temporal association of OCD and subsequent PD remained unclear. METHODS Here, we used Taiwan National Health Insurance Research Database and included the data of 28,722 patients with OCD ( International Classification of Diseases, Ninth Revision, Clinical Modification code: 300.3) and 287,220 matched controls between 2001 and 2009. They were followed until the end of 2011 to identify diagnosis of new-onset PD ( International Classification of Diseases, Ninth Revision, Clinical Modification code: 332.0). The frequency of psychiatric outpatient visits for OCD per year (<5, 5-10, and >10) was identified as a proxy of OCD severity. RESULTS Using the stratified Cox regression model, the hazard ratio of developing PD among patients with OCD was 2.70 (95% confidence interval = 1.74-4.18) compared with matched controls. Among patients with OCD, those with >10 psychiatric outpatient visits per year for OCD (hazard ratio = 3.18, 95% confidence interval = 2.06-4.93) were more likely to develop PD during the follow-up period compared with those with <5 psychiatric outpatient visits per years for OCD. CONCLUSIONS OCD was found to be an independent risk factor for PD. The mechanisms underlying the temporal association between OCD and subsequent PD require further investigation.
10.1097/PSY.0000000000001120
pubmed_1142_11784
Insulin activity is generally determined by an in vivo rabbit blood glucose drop assay in research and industriel laboratories. The humane experimental techniques imply the use of alternative invertebrate organisms in place of animals, known as replacement rule of the 3Rs. In this study, we report an alternative in vivo extracellular glucose drop assay using unicellular invertebrate Tetrahymena thermophila to replace the use of rabbit and mouse. This assay has four major steps; growing cells, starving cells, treatment of cells and measurement of glucose drop. In this assay, 0.2 mg/ml of human, porcine and bovine insulins dropped extracellular glucose level to 16%, 14% and 12%, respectively in ten minutes. In addition, mammalian insulins respectively increased the cell area about 19%, 15%, and 16% at 6th hour with statistically significant effect on the cell growth, but not in the cell viability. The results showed that the in vivo Tetrahymena thermophila extracellular glucose drop assay could be used as an alternative assay to replace the mouse or the rabbit insulin blood glucose drop assay.
10.1016/j.ejop.2021.125803
pubmed_643_14617
The incorporation of magnetic impurities into semiconductor nanocrystals with size confinement promotes enhanced spin exchange interaction between photogenerated carriers and the guest spins. This interaction stimulates new magneto-optical properties with significant advantages for emerging spin-based technologies. Here we observe and elaborate on carrier-guest interactions in magnetically doped colloidal nanoplatelets with the chemical formula CdSe/Cd1-MnS, explored by optically detected magnetic resonance and magneto-photoluminescence spectroscopy. The host matrix, with a quasi-type II electronic configuration, introduces a dominant interaction between a photogenerated electron and a magnetic dopant. Furthermore, the data convincingly presents the interaction between an electron and nuclear spins of the doped ions located at neighboring surroundings, with consequent influence on the carrier's spin relaxation time. The nuclear spin contribution by the magnetic dopants in colloidal nanoplatelets is considered here for the first time.
10.1021/acs.jpclett.9b01999
pubmed_242_2498
In urban areas, primary and secondary organic aerosols are typically considered to originate from vehicular traffic emissions. However, industrial emissions within or in the vicinity of urban areas may also be significant contributors to carbonaceous aerosol concentrations. This hypothesis was tested and validated in two urban areas in Spain. The observed unusual dominance of organic carbon (OC) over elemental carbon (EC), the analysis of the variability of OC, EC and OC/EC and their correlation with transport patterns suggested the presence of OC sources associated with industrial activities. A methodology based on chemical speciation of particulate matter (PM) followed by the application of receptor modelling techniques allowed for the identification of the specific industrial sources of OC, which were linked to primary OC emissions from a grain drying plant (cereal) and to secondary OC formation from paper production activities (paper mills), as well as from urban sources and biogenic emissions. This work presents an integrated approach to identifying and characterizing of industrial sources of carbonaceous aerosols in urban areas, aiming to improve the scarce body of literature currently available on this topic.
10.1007/s11356-015-4228-x
pubmed_407_19640
The World Health Organization is currently revising the International Classification of Disease, 10th Revision (ICD-10). A Neurology Task Force Advisory Group [TAG] has been charged with producing a revision that reflects scientific advances and new concepts of pathophysiology since 1992. The ICD codes are used globally to report mortality and morbidity statistics, and they play a vital role in health care planning, training, and allocation of health care resources in many countries. Although used by physicians and hospitals at all levels, the primary users of the ICD codes are primary health care providers, which, particularly in low income countries, include nurses, clinical assistants, and health officers. The TAG, which consists of representatives of major international subspecialty groups such as the International League Against Epilepsy (ILAE), has published draft codes that are available online for public comment.
10.1111/j.1528-1167.2012.03550.x
pubmed_1115_16185
Mammalian two-hybrid assay is a convenient, powerful tool to investigate protein-protein interactions in vivo. In particular, this method has a major advantage over the better known yeast version in that one can study interactions between mammalian proteins that may not fold correctly in yeast or that require post-translational modification or external stimulation that are not present in yeast.
10.1385/1-59259-762-9:327
pubmed_1058_13055
OBJECTIVE The purpose of our study was to evaluate the predictive power of early postinfarction stress testing in survivors of uncomplicated MI treated with thrombolytics. METHODS The study population consisted of 102 consecutive, thrombolyzed survivors (56 +/- 11 years) of acute, transmural myocardial infarction with uncomplicated postinfarction course. All patients were clinically stable in the postinfarction period and underwent cycle ergometry, 99mTc perfusion scintigraphy and dobutamine stress-echocardiography within three weeks after the acute event. Coronary angiography was used to determine the extent of CAD, LV ejection fraction (LVEF), TIMI grade and residual stenosis of the infarct-related coronary artery. A follow up questionnaire was performed one year after hospital discharge to determine the relation to the occurrence of cardiac events (unstable angina, reinfarction, PTCA, bypass surgery and death). RESULTS 30 patients developed 34 cardiac events. Four patients died. Two thirds of the 'cardiac events' in the year of follow-up were revascularization procedures mostly selected by evidence of ischemia on 99mTc perfusion scintigraphy and/or stress-echocardiography. These two methods were significantly associated with the development of new cardiac events (stress-echocardiography: p < 0.01; 99mTc perfusion scintigraphy: p < 0.006). Parameters of bicycle ergometry and variables of coronary angiography were not related to an increased risk of future cardiac events. The number of 'hard cardiac events'--death or nonfatal AMI--was too small (8%) in these patients who are able to exercise to make statistical comparisons. CONCLUSIONS The study underlines the necessity of early noninvasive risk assessment to identify patients at a greater risk among survivors of uncomplicated AMI treated with thrombolytics who are clinically stable in the early postinfarction period. PTCA and coronary bypass surgery is performed in one third of these patients selected mostly by evidence of ischemia on 99mTc perfusion scintigraphy and/or stress-echocardiography. Results of bicycle ergometry are of limited value in these patients within the first year after acute myocardial infarction.
pubmed_1058_13055
pubmed_662_11758
Isometric rigor tension development of glycerinated rabbit psoas muscle fibers in a medium, due to the formation of rigor complexes, was estimated at varying ATP concentrations from 0 to 2.5 mM and pH values from 6.75 to 8.20. The dissociation of rigor complexes was also estimated under the same conditions. When muscle fibers developed rigor tension from the relaxed and rigor states, the magnitude of rigor tension increased with increasing concentration of ATP. Transition between rigor and relaxation in single fibers occurred discontinuously at constant levels (critical levels) of ATP which were determined by pH. The critical concentrations of ATP necessary for inducing the transitions between rigor and relaxed states were also increased exponentially with increased pH. Incomplete repetition of tension development by the same fiber was also observed. This incomplete reversibility was divided into two types: one which showed a decay in rigor tension and another which showed no decay. The reason for the incomplete reversibility was discussed
10.1016/0304-4165(81)90116-1
pubmed_203_16558
Visibility of a central target Gabor element often improves in the presence of collinear flankers. Such lateral interactions may reflect fundamental mechanisms underlying the perceptual integration of contours in early vision. We recently reported (Freeman, Sagi, & Driver, 2001) attentional modulation of these interactions. Here, we test whether this modulation is task dependent. Subjects had to detect a near-threshold central target while performing a secondary discrimination task on one pair of flankers that could appear with another distractor pair (one pair collinear with the target, the other orthogonal). Central target thresholds were lowered when collinear flankers were judged for the secondary task, but only when this task concerned the global spatial relationship between these flankers (discrimination of their Vernier offset or global orientation). Other secondary tasks involving discriminating the local orientations, contrasts, or colors of the relevant flanker pair produced no such attentional modulation. However, this task-dependent modulation was observed only when two flanker pairs were present, not for displays with only a single flanker pair. Top-down modulation of lateral interactions may function to select between overlapping potential contours whenever the global spatial properties of one are task relevant.
10.3758/bf03193519
pubmed_343_15482
Self-reported anthropometric data in web-based weight loss interventions may be inaccurate. We studied the agreement between online self-reported and measured weight in the course of the POEmaS randomized controlled trial. Measured weight was not different from reported one (-0.4 kg; 95%CI -0.93 to 0.12). 95.6% of the cases were within the limits of agreement (Bland-Altman method). Self-reported weight collected online was accurate, which suggests that interventions and outcomes assessment can rely on these data.
10.3233/SHTI190572
pubmed_175_13158
In an aquatic environment, the presence of Bisphenol A (BPA) adversely affects reproduction, biology, behavior, gonads, and early larval development of fish due to being endocrine-disrupting compound. In addition, the detected concentration of BPA in water bodies is reported to be higher than 0.41 μg/L. As an alternative tool, sperm cells are used in toxicological assays for the reliable and practical assessment. For these reasons, we examined the effects of in vitro exposure of BPA on sperm quality of chub Squalius oriantalis and Padanian barbel Barbus plebejus. Spermatozoa were exposed to lower concentrations (0, 0.5, 1.25, 2.5, and 5 µg/L) of BPA for 2 h. The enzymatic activities [glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD)] and lipid peroxidation (MDA) were evaluated in spermatozoa. The results demonstrated that BPA exposure significantly decreased activities of SOD and GSH-Px but increased CAT activity and lipid peroxidation (MDA). Compared to control, the percentage and duration of sperm motility significantly decreased. Overall, spermatozoa clearly showed the sensitivity to lower concentrations of BPA.
10.1080/01480545.2020.1726379
pubmed_313_2395
BACKGROUND/AIMS Extensive studies have demonstrated that Bleomycin (BLM) is a glycopeptide antibiotic that has been used as an anticancer chemotherapeutic reagent. It can induce both single- and double-strand DNA damage, inhibit synthesis of DNA, suppress proliferation, and induce apoptosis in cancer cells. Smad signaling transducers are considered as important molecules in tumor development and progression, and may closely be related to the biological behaviors of some malignant carcinomas, including gastric cancer. METHODS The effects of different concentrations of BLM on the proliferation, cell cycle, apoptosis, migration, and invasion on gastric cancer cell lines MKN45 and AGS were assayed by using CCK-8 assay, Annexin V/PI double staining, PI staining, and transwell assay. Western blot and Immunohistochemistry were applied to analyze the potential mechanism(s). RESULTS BLM treatment resulted in a low proliferation, high apoptosis, low migration and invasion in MKN45 and AGS cells. Furthermore, the possible mechanisms underlying that Smad3 activity could be changed after binding with BLM, and subsequently the Smad signaling pathway had a cascade response. CONCLUSION These results highlight BLM as an exciting theme for gastric cancer treatment, which may represent an effective clinical therapeutic reagent for gastric cancer patients.
10.1159/000453192
pubmed_458_19788
In this study, we have begun to analyze phosphotyrosyl and associated proteins present in a DT40 chicken B cell line overexpressing the nonreceptor protein-tyrosine kinase, Syk. An anti-phosphotyrosine antibody was used to select tyrosine-phosphorylated proteins. After tryptic digestion, peptides were subjected to a beta-elimination reaction and phosphotyrosine-containing peptides were enriched via immobilized metal affinity chromatography. Several known substrates and candidate substrates for Syk and the location of 22 tyrosine phosphorylation sites were identified.
10.1021/pr049967i
pubmed_265_14871
We have shown previously that de novo methylation activities persist in mouse embryonic stem (ES) cells homozygous for a null mutation of Dnmt1 that encodes the major DNA cytosine methyltransferase. In this study, we have cloned a putative mammalian DNA methyltransferase gene, termed Dnmt2 , that is homologous to pmt1 of fission yeast. Different from pmt1 in which the catalytic Pro-Pro-Cys (PPC) motif is 'mutated' to Pro-Ser-Cys, Dnmt2 contains all the conserved methyltransferase motifs, thus likely encoding a functional cytosine methyltransferase. However, baculovirus-expressed Dnmt2 protein failed to methylate DNA in vitro . To investigate whether Dnmt2 functions as a DNA methyltransferase in vivo , we inactivated the Dnmt2 gene by targeted deletion of the putative catalytic PPC motif in ES cells. We showed that endogenous virus was fully methylated in Dnmt2 -deficient mutant ES cells. Furthermore, newly integrated retrovirus DNA was methylated de novo in infected mutant ES cells as efficiently as in wild-type cells. These results indicate that Dnmt2 is not essential for global de novo or maintenance methylation of DNA in ES cells.
10.1093/nar/26.11.2536
pubmed_367_5829
The major transactivator protein IE2p86 of human cytomegalovirus (HCMV) has previously been shown to undergo posttranslational modification by the covalent attachment of SUMO proteins, termed SUMOylation, which occurs at two lysine residues located at amino acid positions 175 and 180. Mutation of the acceptor lysines resulted in the abrogation of IE2p86 SUMOylation in mammalian cells and a strong reduction of IE2p86-mediated transactivation. In this paper, we identify an additional SUMO interaction motif (SIM) within IE2p86, which mediates noncovalent binding to SUMO, as shown by yeast two-hybrid analyses. Transient-expression experiments revealed that an IE2p86 SIM mutant exhibited significantly reduced SUMOylation, strongly suggesting that noncovalent SUMO interactions affect the efficacy of covalent SUMO coupling. In order to define the relevance of IE2p86 SUMO interactions for viral replication, recombinant viruses originating from two different HCMV strains (AD169 and VR1814) were generated. Analysis of viruses expressing SUMOylation-negative IE2p86 revealed strongly impaired replication due to reduced viral DNA and protein accumulation, as well as diminished initiation of immediate-early gene expression. The additional introduction of the SIM mutation into the viral genome did not further compromise viral replication but resulted in altered expression of viral proteins at late times postinfection. In summary, this paper clearly shows that IE2p86 SUMOylation is necessary for efficient replication of the HCMV laboratory strain AD169 and the clinical isolate VR1814 and thus for the in vivo function of this viral transcription factor.
10.1128/JVI.01525-09
pubmed_482_17502
Transcription initiation constitutes a major checkpoint in gene regulation across all living organisms. Control of chromatin function is tightly linked to this checkpoint, which is best illustrated by the SAGA coactivator. This evolutionary conserved complex of 18-20 subunits was first discovered as a Gcn5p-containing histone acetyltransferase, but it also integrates a histone H2B deubiquitinase. The SAGA subunits are organized in a modular fashion around its central core. Strikingly, this central module of SAGA shares a number of proteins with the central core of the basal transcription factor TFIID. In this review I will compare the SAGA and TFIID complexes with respect to their shared subunits, structural organization, enzymatic activities and chromatin binding. I will place a special emphasis on the ancestry of SAGA and TFIID subunits, which suggests that these complexes evolved to control the activity of TBP (TATA-binding protein) in directing the assembly of transcription initiation complexes.
10.1016/j.bbagrm.2020.194604
pubmed_217_15749
OBJECTIVE To investigate the reliability of inspection-based classification of sagittal gait patterns in children with bilateral spastic cerebral palsy (CP). METHOD Video clip recordings of gait patterns and sagittal kinematic data obtained by a computerized motion analysis system from 91 patients with bilateral spastic CP were reviewed. The abnormal gait patterns were classified into 4 groups using the method described by Rodda et al. Visual observation-based classification (visual classification) was compared with classification by 3D analysis-based methods (3D classification). The reliabilities of visual classifications made by an experienced physician and a trainee physician were analyzed. RESULTS The consistency of inspection-based gait classification using kinematic data analysis was demonstrated by an experienced physician (Kappa coefficient (k)=0.67, p<0.001). However, the consistency was low for the trainee physician (k=0.37, p<0.001). Group III (apparent equinus) was commonly confused with group IV (crouch gait) by the trainee physician, resulting in lower agreement for those two evaluation groups than for other patterns. Video observation showed low reliability in comparisons made between the experienced and the trainee physician (k=0.37, p<0.001). CONCLUSION There was substantial agreement of gait classification between video observation and kinematic data analysis by the experienced physician, but not by the trainee physician. Low reliability was also demonstrated for inspection-based gait classification.
10.5535/arm.2011.35.3.354
pubmed_828_17668
The authors compared and analyzed the correlated meridians in Internal Classic and Study on the Eight Extra-Channels and Vessels by clinical observation on acupuncture for treatment of oculomotor paralysis and reorganization research on ancient related literature, and course of meridians and collaterals, manifestations of disease and function were used as indexes. The present symptoms of oculomotor paralysis (paralytic strabismus) are well consistent with the delineation in Internal Classic such as inability to open eyes, blurring of vision and pain of outer canthus. The results indicate that it is important to regulate the Qiao Meridian function for acupuncture treatment of oculomotor paralysis; the method of the twelve regular meridians and the eight extra-meridians is different for treatment of this disease, for the twelve regular meridians treating the superficiality and the eight extra-meridians treating the origin, and the combinativue use of the two methods can display the TCM theory thought and the characteristic of simultaneous treatment of principal and subordinate symptoms; there is closely relation between musculature diseases and pathological change of oculomotor paralysis and it is helpful in perfecting therapeutic principles and research methods.
pubmed_828_17668
pubmed_76_16538
The stable tyrosine radical in photosystem II, YD*, has been studied by ESR and ENDOR spectroscopies to obtain proton hyperfine coupling constants from which the electron spin density distribution can be deduced. Simulations of six previously published ESR spectra of PSII (one at Q band; five at X band, of which two were after specific deuteration and two others were of oriented membranes) can be achieved by using a single set of magnetic parameters that includes anisotropic proton hyperfine tensors, an anisotropic g tensor, and noncoincident axis systems for the g and A tensors. From the spectral simulation of the oriented samples, the orientation of the phenol head group of YD* with respect to the membrane plane has been determined. A similar orientation for YZ*, the redox-active tyrosine in PSII that mediates electron transfer between P680 and the oxygen-evolving complex, is expected. ENDOR spectra of YD* in PSII preparations from spinach and Synechocystis support the set of hyperfine coupling constants but indicate that small differences between the two species exist. Comparison with the results of spectral simulations for tyrosyl radicals in ribonucleotide reductase from prokaryotes or eukaryotes and with in vitro radicals indicates that the spin density distribution remains that of an odd-alternant radical but that interactions with the protein can shift spin density within this basic pattern. The largest changes in spin density occur at the tyrosine phenol oxygen and at the ring carbon para to the oxygen, which indicates that mechanisms exist in the protein environment for fine-tuning the chemical and redox properties of the radical species.
10.1021/bi00162a028