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41.
A nationwide study of intracellular drug metabolite concentrations in children prescribed 6-mercaptopurine for the treatment of lymphoblastic leukaemia was carried out to assess interpatient variability at a standardised dose. Nine children (2% of the total) had completely undetectable metabolites, indicative of non-compliance. Five were adolescents, but otherwise they had no obvious distinguishing characteristics. Not taking any 6-mercaptopurine at all is uncommon, but the problem cannot be predicted. The total number of children who do not comply cannot be determined from this study, but the nine children described represent only a fraction of these. 相似文献
42.
Zhao P Cao J Zhao LJ Qin ZL Ke JS Pan W Ren H Yu JG Qi ZT 《第二军医大学学报》2006,27(5):506-506
The nucleocapsid (N) protein of SARS-coronavirus (SARS-CoV) is the key protein for the formation of the helical nucleocapsid during virion assembly. This protein is believed to be more conserved than other proteins of the virus, such as spike and membrane glycoprotein. In this study, the N protein of SARS-CoV was expressed in Escherichia coli DHSalpha and identified with pooled sera from patients in the convalescence phase of SARS. A plasmid pCI-N, encoding the full-length N gene of SARS-CoV, was constructed. Expression of the N protein was observed in COS1 cells following transfection with pCI-N. The immune responses induced by intramuscular immunization with pCI-N were evaluated in a murine model. Serum anti-N immunoglobutins and splenocytes proliferative responses against N protein were observed in immunized BALB/c mice. The major immunoglobulin G subclass recognizing N protein was immunoglobulin G2a, and stimulated splenocytes secreted high levels of gamma interferon and IL-2 in response to N protein. More importantly, the immunized mice produced strong delayed-type hypersensitivity (DTH) and CD^8+ CTL responses to N protein. 相似文献
43.
Beatriz Togoro Ferreira da Silva Livia Tosi Trevelin Ananda Carolina Schroeter Amanda Endres Willers Paulo Francisco Cesar Adriana Bona Matos 《European journal of oral sciences》2021,129(1):e12754
This study investigated the effect of irradiation with an erbium‐doped yttrium aluminium garnet (Er:YAG) laser and coating with silica on the surface characteristics, bond strength, and flexural strength of dental zirconia. Three hundred and forty‐three standard zirconia specimens were created, and 49 were assigned to each of seven surface treatment groups: (i) no treatment; Er:YAG laser (80 mJ/2 Hz) with pulse widths of 50 μs (ii), 100 μs (iii), 300 μs (iv), or 600 μs (v); or tribochemical silica coating at the partially sintered stage (vi) or after sintering was complete (vii). All specimens were sintered after the surface treatments, except for the group in which specimens were sintered before treatment. The study outcomes were roughness, surface loss, microshear bond strength (μSBS), and biaxial flexural strength (BFS). Mean roughness and surface loss values were significantly higher in specimens from irradiated groups than in those from silica‐coated groups. Regarding μSBS, after aging, specimens from all experimental groups presented very low and similar μSBS values, irrespective of the surface treatment. Silica coating after sintering yielded the highest BFS (1149.5 ± 167.6 MPa), while coating partially sintered specimens with silica resulted a BFS (826.9 ± 60.9 MPa) similar to that of the untreated control group (794.9 ± 101.7 MPa). Laser treatments, irrespective of pulse width used, significantly decreased the BFS. In the group treated with laser at 300 μs pulse width, specimens exhibited the lowest BFS value (514.1 ± 71.5 MPa). Adhesion to zirconia was not stable after aging, regardless of the surface treatment implemented. 相似文献
44.
R Endres 《BMC biophysics》2012,5(1):18-3
ABSTRACT: Advances in computational biology allow systematic investigations to ascertain whether internal chemical gradients can be maintained in bacteria -- an open question at the resolution limit of fluorescence microscopy. While it was previously believed that the small bacterial cell size and fast diffusion in the cytoplasm effectively remove any such gradient, a new computational study published in BMC Biophysics supports the emerging view that gradients can exist. The study arose from the recent observation that phosphorylated CtrA forms a gradient prior to cell division in Caulobacter crescentus, a bacterium known for its complicated cell cycle. Tropini et al. (2012) postulate that such gradients can provide an internal chemical compass, directing protein localization, cell division and cell development. More specifically, they describe biochemical and physical constraints on the formation of such gradients and explore a number of existing bacterial cell morphologies. These chemical gradients may limit in vitro analyses, and may ensure timing control and robustness to fluctuations during critical stages in cell development. 相似文献
45.
Saskia H. Meves Thomas Hummel Heinz G. Endres Nora Mayböck Andreas F. C. Kaiser Kay D. Schröder Katja Rüdiger Ursula Overbeck Achim Mumme Andreas Mügge Horst Neubauer 《Journal of thrombosis and thrombolysis》2014,37(2):190-201
Although acetylsalicylic acid (ASA, aspirin) reduces the risk of ischemic events in patients with atherosclerosis, a substantial number of incidents continue to occur. As only limited data exist we evaluated the antiplatelet effectiveness of ASA in patients with different manifestations of atherosclerosis as in cerebrovascular, coronary artery and peripheral arterial disease (CVD, CAD, PAD). For the evaluation of the antiplatelet effectiveness of ASA we used whole blood aggregometry (Chrono-log Model 590). The patients in the different subgroups received ASA 100, 200 or 500 mg daily. We analysed 737 consecutive patients: 47.5 % with CVD, 33.6 % with CAD, and 18.9 % with PAD. We identified 28.0 % of the CVD, 18.1 % of the CAD and 21.6 % of the PAD patients to be ASA low-responder (ALR). Comparing subgroups treated with 100 mg ASA, 36.4 % were ALR in the CVD group as were 13.1 % of the CAD and 21.6 % of the PAD patients. Multivariate regression analysis revealed an odds ratio for being ALR of 4.50 (95 % confidence interval (CI) 1.70–11.9) when 100 mg and of 2.97 (95 % CI 1.58–5.60) when 200 mg ASA was taken compared to a dose of 500 mg. Despite the proven benefits of antiplatelet therapy in the secondary prevention of atherosclerotic disease, current antiplatelet management is suboptimal as up to 36 % of patients failed to achieve an adequate platelet inhibitory effect. Our findings may explain, at least in part, the high rates of cardiovascular events observed in the course of atherothrombotic disease and support the need to improve antiplatelet therapy. 相似文献
46.
The epidemiology of hyperuricaemia and gout in Taiwan aborigines 总被引:4,自引:1,他引:4
To determine the prevalence of hyperuricaemia, gout and gout-related
factors in Central Taiwan Atayal aborigines, 342 subjects over 18 yr old
were interviewed and examined. A questionnaire was designed to screen for
signs and symptoms of gout and gout-related risk factors. Serum uric acid,
triglyceride and creatinine were measured in all subjects. The prevalence
of hyperuricaemia was 41.4% and that of gout 11.7% in aborigines. The uric
acid level was 7.9+/-1.7 mg/dl in males and 5.7+/-1.5 in females, and
differed significantly under age 70 yr (P < 0.001). Significantly
increased triglyceride, creatinine and alcoholism was found in gouty
patients compared with non-gouty patients. In 40 cases with gout, 54% had
tophi and 35% of their first- degree relatives had gout. The high
prevalence of hyperuricaemia and gout in Taiwan Atayal aborigines, a
significant family predisposition, increased creatinine level and
alcoholism suggest multiple factors affecting the hyperuricaemia.
相似文献
47.
Ortiz-Alvarez O; Cabral D; Prendiville JS; Stringer D; Petty RE; Malleson PN 《Rheumatology (Oxford, England)》1997,36(2):280-284
Two children are reported in whom intestinal pseudo-obstruction was the
initial manifestation of systemic sclerosis. Gastrointestinal symptoms and
skin changes resolved or improved in both children following treatment with
prednisone and penicillamine (case 1) or methotrexate (case 2), although
radiological changes of the gastrointestinal tract persisted at 3 and 2 yr
of follow-up, respectively.
相似文献
48.
Coakley G; Mok CC; Hajeer AH; Ollier WE; Turner D; Sinnott PJ; Hutchinson IV; Panayi GS; Lanchbury JS 《Rheumatology (Oxford, England)》1998,37(9):988-991
OBJECTIVE: To examine whether promoter polymorphisms associated with
variation in interleukin-10 (IL-10) production are relevant to the
development of rheumatoid arthritis (RA) or Felty's syndrome (FS). METHODS:
DNA was obtained from 44 FS patients, 117 RA patients and 295 controls. The
promoter region between -533 and - 1120 was amplified by polymerase chain
reaction, and polymorphisms detected by restriction enzyme digest or
sequence-specific oligonucleotide probing. RESULTS: We found no significant
difference in allele or haplotype frequencies between the groups.
CONCLUSION: There is no association between FS or RA and these recently
identified IL-10 promoter polymorphisms. Other genetic or environmental
factors could explain the alterations in IL-10 levels seen in these
conditions.
相似文献
49.
50.
Marco Gerlinger Sergio A Quezada Karl S Peggs Andrew JS Furness Rosalie Fisher Teresa Marafioti Vishvesh H Shende Nicholas McGranahan Andrew J Rowan Steven Hazell David Hamm Harlan S Robins Lisa Pickering Martin Gore David L Nicol James Larkin Charles Swanton 《The Journal of pathology》2013,231(4):424-432
The recognition of cancer cells by T cells can impact upon prognosis and be exploited for immunotherapeutic approaches. This recognition depends on the specific interaction between antigens displayed on the surface of cancer cells and the T cell receptor (TCR), which is generated by somatic rearrangements of TCR α‐ and β‐chains (TCRb). Our aim was to assess whether ultra‐deep sequencing of the rearranged TCRb in DNA extracted from unfractionated clear cell renal cell carcinoma (ccRCC) samples can provide insights into the clonality and heterogeneity of intratumoural T cells in ccRCCs, a tumour type that can display extensive genetic intratumour heterogeneity (ITH). For this purpose, DNA was extracted from two to four tumour regions from each of four primary ccRCCs and was analysed by ultra‐deep TCR sequencing. In parallel, tumour infiltration by CD4, CD8 and Foxp3 regulatory T cells was evaluated by immunohistochemistry and correlated with TCR‐sequencing data. A polyclonal T cell repertoire with 367–16 289 (median 2394) unique TCRb sequences was identified per tumour region. The frequencies of the 100 most abundant T cell clones/tumour were poorly correlated between most regions (Pearson correlation coefficient, –0.218 to 0.465). 3–93% of these T cell clones were not detectable across all regions. Thus, the clonal composition of T cell populations can be heterogeneous across different regions of the same ccRCC. T cell ITH was higher in tumours pretreated with an mTOR inhibitor, which could suggest that therapy can influence adaptive tumour immunity. These data show that ultra‐deep TCR‐sequencing technology can be applied directly to DNA extracted from unfractionated tumour samples, allowing novel insights into the clonality of T cell populations in cancers. These were polyclonal and displayed ITH in ccRCC. TCRb sequencing may shed light on mechanisms of cancer immunity and the efficacy of immunotherapy approaches. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献