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61.
62.
Goldberg I Gilburd B Kravitz MS Kivity S Chaim BB Klein T Schiffenbauer Y Trubniykovr E Brenner S Shoenfeld Y 《Clinical & developmental immunology》2005,12(1):85-90
Background: There are several mechanisms to describe allergic drug
reactions yet the methods to diagnose them are limited.
Objective: To compare several conventional clinical and laboratory
methods to diagnose skin reactions to drugs
to a new method of diagnosing drug reactions by the CellScan system.
Methods: The study entailed 21 patients who were diagnosed as
suffering from drug eruptions, and 105 healthy controls with no history of drug
allergy. The drugs were classified into two groups according to suspicion of
causing drug allergy: high and low. Most of the patients were on more than
one drug, leading to 41 patient-drug interactions (assays). Histamine
releasing test (HRT), interferon (INF)-γ releasing test and CellScan
examination were performed on lymphocytes of the patients and controls.
Results: The HRT was interpreted as positive in 9 out of 18 (50%)
patients and in 13 out of 35 (37%) assays. Based on the INF-γ releasing test,
positive results were observed in 16 out of 21 (76%) patients and in 24 out of 41
(59%) assays. In the CellScan test (CST), positive results were observed in 17
out of 21 (81%) patients and in 29 out of 41 (71%) assays. The rate of identifying
the drug for eruption in the high suspicion level drugs was 9 out of 22 (41%)
assays in the HRT, 20 out of 24 (83%) assays in the INF-γ releasing test, and 21
out of 24 (87%) studies with the CellScan method. The rate of determining of
the drug that caused the eruption in the low suspicion level drugs was 4 out of
13 (31%) in the HRT, 4 out of 17 (24%) assays in the INF-γ releasing test, and 8
out of 17 (47%) analyses in the CST. When examined
in the CellScan, 99 out of 105 (94%) controls were interpreted as negative.
Conclusion: This preliminary study indicates that the CellScan seems to
be an easy and promising method for the detection of drugs responsible for
adverse skin reactions. In contrast to the HRT and to the Interferon-γ secretion
test, the CellScan method is characterized by its ability to track and monitor
the reaction of individual cells. By measuring the kinetic parameters of selected
cells before and after adding the suspected drug, we were able to identify
the culprit drug. The CellScan method had the highest sensitivity, and the
interferon-γ secretion test had the highest specificity for detection of the culprit
drug. In contrast, the analysis of 105
normal control sera disclosed a high specificity of 94% for the CellScan method. 相似文献
63.
Multilocus haplotype analyses reveal association between 5 novel IL-15 polymorphisms and asthma 总被引:5,自引:0,他引:5
Kurz T Strauch K Dietrich H Braun S Hierl S Jerkic SP Wienker TF Deichmann KA Heinzmann A 《The Journal of allergy and clinical immunology》2004,113(5):896-901
BACKGROUND: IL-15 is a T(H)1-related cytokine that is involved in the inflammatory response in various infectious and autoimmune diseases. IL-15 has recently been shown to be upregulated in T-cell-mediated inflammatory disorders. The observations suggest a potential role for this cytokine in a variety of pathologic conditions, including T(H)1-mediated and T(H)2-mediated inflammatory diseases. OBJECTIVE: In this study, we searched for single nucleotide polymorphisms in the whole IL-15 gene and investigated their association with inflammatory and/or atopic phenotypes. METHODS: The screening for single nucleotide polymorphisms was performed by single-strand conformation polymorphism analysis. Genotyping of the identified polymorphisms was performed by restriction fragment length polymorphism. Genotypic association analysis used the Armitage trend test. Haplotype frequency estimation and subsequent testing for differences between cases and controls were performed by using the programs FASTEHPLUS and FAMHAP. RESULTS: We identified 5 novel noncoding nucleotide sequence variants, all of which were typed in our asthmatic, our atopic, and our control population. According to the Armitage trend test, none of the 5 polymorphisms is associated with the phenotype bronchial asthma or atopy. However, multilocus haplotype analysis based on simulations to find out whether the haplotype frequencies differed between cases and controls by using the program FAMHAP yielded a P value of 6.1 x 10(-5) in the asthmatic versus the control population, which is highly significant. Furthermore, we obtained a nominally significant result of P=.0232 for the atopic versus the control population by using FAMHAP. CONCLUSION: These results strongly underscore previous findings that suggest a potential role of this cytokine in allergic diseases. 相似文献
64.
Zelinski-Wooten MB; Slayden OD; Chwalisz K; Hess DL; Brenner RM; Stouffer RL 《Human reproduction (Oxford, England)》1998,13(2):259-267
Large doses of antiprogestin typically disrupt menstrual cyclicity. A
chronic low-dose regimen of the potent new antiprogestin ZK 137 316, which
permits continued menstrual cyclicity but alters gonadal- reproductive
tract activity, was established. Rhesus monkeys received vehicle (n = 6) or
0.01 (n = 8), 0.03 (n = 8) or 0.1 (n = 5) mg ZK 137 316/kg body weight
daily for five menstrual cycles (C-1 to C-5). Oestradiol, progesterone and
gonadotrophin profiles were normal during cycles involving vehicle and 0.01
and 0.03 mg ZK 137 316/kg body weight. In the 0.1 mg/kg group, mid-cycle
oestradiol and gonadotrophin surges, and subsequent progesterone
production, were absent in C-3 and C-5. Ovarian cyclicity was accompanied
by timely menstruation in the vehicle and 0.01 mg/kg groups. By C-3, half
the animals in the 0.03 mg/kg group and all animals in the 0.1 mg/kg group
were amenorrhoeic. A corpus luteum was noted during the mid-luteal phase of
C-5 in the vehicle, 0.01 mg/kg and 0.03 mg/kg groups. Large antral and
cystic follicles were evident in the 0.1 mg/kg group. Thus, a daily
treatment with 0.01 mg/kg ZK 136317 permitted normal menstrual cyclicity in
macaques. While the daily administration of 0.03 mg/kg ZK 136 317 allowed
ovarian cyclicity, menstruation was disrupted in some animals. Increasing
the dose to 0.1 mg/kg antagonized pituitary function and resulted in
anovulation and amenorrhoea. A chronic low-dose regimen of the
antiprogestin ZK 137 316, which permits normal ovarian/menstrual cyclicity,
has potential as a contraceptive in women.
相似文献
65.
Lichtenberg A Dumlu G Walles T Maringka M Ringes-Lichtenberg S Ruhparwar A Mertsching H Haverich A 《Biomaterials》2005,26(5):555-562
Investigation of cell abilities to growth, proliferation and (de)-differentiation in a three-dimensional distribution is an important issue in biotechnological research. Here, we report the development of a new bioreactor for three-dimensional cell culture, which allows for co-cultivation of various cell types with different culture conditions in spatial separation. Preliminary results of neonatal rat cardiomyocyte cultivation are shown. Isolated neonatal rat cardiomyocytes were cultured in spatial separated bioreactor compartments in recirculating medium on a biodegradable fibrin matrix for 2 weeks. Glucose, lactate, and lactate dehydrogenase (LDH), pO2, pCO2, and pH levels were monitored in the recirculated medium, daily. Morphological characterization of matrix and cells was assessed by hematoxylin and eosin staining, and MF-20 co-immunostaining with 4',6-diamidino-2-phenylindole (DAPI). Cell viability was determined by LIVE/DEAD staining before cultivation and on day 3, 7, and 14. The optimized seeding density in the matrix was 2.0 x 10(7) cells retaining cellular proportions over the cell culture period. The bioreactor allows the maintenance of physiologic culture conditions with aerobic cell metabolism (low release of lactate, LDH), a high oxygen tension (pO2-183.7 +/- 18.4 mmHg) and physiological pH values (7.4 +/- 0.02) and a constant level of pCO2 (43.1 +/- 2.9) throughout the experimental course. The cell viability was sufficient after 2 weeks with 82 +/- 6.7% living cells. No significant differences were found between spatial separated bioreactor compartments. Our novel multifunctional bioreactor allows for a three-dimensional culture of cells with spatial separation of the co-cultured cell groups. In preliminary experiments, it provided favorable conditions for the three-dimensional cultivation of cardiomyocytes. 相似文献
66.
Leanne Tamm Jeffery N. Epstein Richard E.A. Loren Stephen P. Becker Sarah B. Brenner Morgan E. Bamberger 《Journal of clinical child and adolescent psychology》2019,48(2):S131-S145
This goal of this study was to assess the initial feasibility and efficacy of a play-based intervention targeting executive functions (EF) and parent–child relationships in preschoolers compared with an active control group. Preschoolers with EF deficits (M age = 3.7 ± 0.47, predominantly White boys) and their parents were randomized to intervention (n = 36) or active control (n = 32) conditions. Child performance on EF tasks, parent and masked teacher ratings of EF and behavior, and masked clinician ratings of severity were collected at baseline and at 3 and 6 months postbaseline. Partial eta-squared effect sizes at .02 or higher comparing performance across the two groups was considered evidence of meaningful, albeit small, intervention effects. Intervention effects were observed for parent ratings of inattention, hyperactivity/impulsivity, and number/severity of problems experienced in various home situations, teacher ratings of severity of problems in various school situations, parent and teacher ratings of overall impairment, and clinician ratings of impairment. Intervention effects for functional improvements were maintained at the 6-month follow-up. No effect of the intervention was observed on the objective EF measures, although parent ratings of emotional control were improved for children in the intervention group. An intervention utilizing play-based activities targeting EF, when administered in a structured way by parents, is a promising approach for improving behavior in preschoolers with self-regulation deficits. More work is needed to investigate potential impact on EF and to disentangle mechanisms of action. It may be that the intervention’s focus on the structure and quality of parent–child interactions is a mediator of outcomes, rather than improved EFs. 相似文献
67.
Beneke R Beyer T Jachner C Erasmus J Hütler M 《European journal of applied physiology》2004,92(4-5):518-523
It is speculated that anaerobic metabolism is the predominant source of energy in karate kumite. However, no experimental proof is currently available. The metabolic cost and fractions of aerobic and anaerobic energy of karate kumite fighting were investigated. Ten male nationally or internationally ranked karateka [means (SD) age 26.9 (3.8) years, height 1.80 (0.08) m, mass 77.2 (12.8) kg] performed two to four fights scheduled and judged like a championship. Oxygen uptake was measured continuously with a portable spirometric device. Blood lactate was determined immediately before, and minute by minute after, each fight. Aerobic, anaerobic alactic and anaerobic lactic energy were calculated from oxygen uptake during the fight (VO2), the fast component of the post-fight oxygen uptake (VO2PCr) above resting values and changes in blood lactate concentration (Net-BLC), respectively. Altogether, 36 fights lasting 267 (61) s were analysed. The referees decisions caused an activity-to-break ratio of approximately 2:1. VO2, VO2PCr, and Net-BLC per fight were 165.3 (52.4) ml.kg–1, 32.2 (7.2) ml.kg–1and 4.2 (1.9) mmol.l–1; the overall energy cost above rest was 334.3 (86.3) kJ per fight. Fractions of aerobic, anaerobic alactic, and lactic energy sources were 77.8 (5.8)%, 16.0 (4.6)%, and 6.2 (2.4)%, respectively. The results indicate a high metabolic rate in karate kumite. However, the acyclic activity profile implies that aerobic metabolism is the predominant source of energy and there is anaerobic supplementation, mainly by high-energy phosphates. 相似文献
68.
CXCR4-transgene expression significantly improves marrow engraftment of cultured hematopoietic stem cells 总被引:4,自引:0,他引:4
Brenner S Whiting-Theobald N Kawai T Linton GF Rudikoff AG Choi U Ryser MF Murphy PM Sechler JM Malech HL 《Stem cells (Dayton, Ohio)》2004,22(7):1128-1133
Hematopoietic stem cells (HSCs) lose marrow reconstitution potential during ex vivo culture. HSC migration to stromal cell-derived factor (SDF)-1 (CXCL12) correlates with CXC chemokine receptor 4 (CXCR4) expression and marrow engraftment. We demonstrate that mobilized human CD34+ peripheral blood stem cells (CD34+ PBSCs) lose CXCR4 expression during prolonged culture. We transduced CD34+ PBSCs with retrovirus vector encoding human CXCR4 and achieved 18-fold more CXCR4 expression in over 87% of CD34+ cells. CXCR4-transduced cells yielded increased calcium flux and up to a 10-fold increase in migration to SDF-1. Six-day cultured CXCR4-transduced cells demonstrated significant engraftment in nonobese diabetic/severe combined immunodeficient mice under conditions in which control transduced cells resulted in low or no engraftment. We conclude that transduction-mediated overexpression of CXCR4 significantly improves marrow engraftment of cultured PBSCs. 相似文献
69.
Nichols SM Bavister BD Brenner CA Didier PJ Harrison RM Kubisch HM 《Human reproduction (Oxford, England)》2005,20(1):79-83
BACKGROUND: A decline in fertility is evident in human females past their middle thirties. This 'reproductive senescence', marked by a sharp decline in pregnancy rates, may be attributed to reductions in numbers of available oocytes and their quality. Because Old World primates exhibit ovarian morphology and physiological control and timing of menstrual cycles closely resembling those of humans, the current study investigated the rhesus macaque as a potential model for human reproductive senescence. METHODS: Ovaries collected from females aged 1-25 years and divided into five age groups were analysed histologically. RESULTS: General ovarian morphology demonstrated significant changes as the females approached menopause. The proportions of primordial and primary follicles all demonstrated significant differences across age groups (primordial: 77.1, 79.9, 69.7, 62.9, 55.1%; primary: 21.5, 18.8, 28.5, 35.2, 43.1% for age groups 1 to 5 respectively; P<0.0001 for both). Samples from females approaching or undergoing the menopausal transition (aged 20-25 years) demonstrated evidence of ovarian senescence, having scattered and atretic follicles, low numbers of primordial follicles and reduced stromal tissue. CONCLUSION: This study supports the value of the rhesus monkey as a model for reproductive ageing because its ovary undergoes follicular reservoir depletion similar to that seen in humans. 相似文献
70.
Michael Heming Xiaolin Li Saskia Räuber Anne K. Mausberg Anna-Lena Börsch Maike Hartlehnert Arpita Singhal I-Na Lu Michael Fleischer Fabian Szepanowski Oliver Witzke Thorsten Brenner Ulf Dittmer Nir Yosef Christoph Kleinschnitz Heinz Wiendl Mark Stettner Gerd Meyer zu Hörste 《Immunity》2021,54(1):164-175.e6
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