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91.
Data for six spatial tests from 927 families of European ancestry, 369 families of Japanese ancestry, and 93 families of Chinese ancestry from the Hawaiian Family Study of Cognition were subjected to unified mixed-model segregation analysis. Father, mother, son, and daughter data sets from each ethnic group were separately age-adjusted and standardized and then separately subjected to transformation procedures to reduce skewness and kurtosis. Families were reassociated prior to segregation analysis. Evidence for a major gene contributing to spatial visualizing ability was obtained for Mental Rotations and Progressive Matrices even with a normalizing transformation which reduced skewness and kurtosis to zero. It was concluded that provision for testing deviation from Mendelian transmission in the unified model protected against false inference of a segregating major gene. Minimizing distributional differences in the components of a data set is an important pretreatment.The results reported here are made possible by the collaboration of a group of investigators (G. C. Ashton, R. C. Johnson, M.-P. Mi, and M. N. Rashad at the University of Hawaii and J. C. DeFries, G. E. McClearn, S. G. Vandenberg, and J. R. Wilson at the University of Colorado) supported by NSF Grant GB 34720 and National Institute of Child Health and Human Development Grant HD 06669. Support for I.B.B. was provided by NIMH Grant MH 14677. 相似文献
92.
Irina Buckle Anthony Johnson Ingrid Leal Rojas Vicky Weinert David P. Sester Kristen Radford Camille Guillerey 《European journal of immunology》2023,53(6):2250118
Growing interest surrounds adoptive cellular therapies utilizing Natural Killer (NK) cells, which can be obtained from various sources, including umbilical cord blood (UCB) and adult peripheral blood (APB). Understanding NK cell receptor expression and diversity in such cellular sources will guide future therapeutic designs. We used a 20-color flow cytometry panel to compare unstimulated and cytokine-activated UCB and APB NK cells. Our analysis showed that UCB NK cells express slightly higher levels of the immune checkpoints PD-1, TIGIT, and CD96 compared to their APB counterparts. Unsupervised hierarchical clustering and dimensionality reduction analyses revealed enrichment in CD56neg as well as mature NKp46neg and CD56+CD16+ NK cell populations in UCB whereas CD57+ terminally differentiated NK cells with variable expression of KIRs and CD16 were found in APB. These populations were conserved following stimulation with IL-12, IL-15, and IL-18. Cytokine stimulation was associated with the downregulation of TIGIT and CD16 on multiple NK cell subsets in UCB and APB. Among UCB CD16− NK cell populations, TIGIT+ NK cells produced more IFN-γ than their TIGIT− counterparts. Our data demonstrate higher immune checkpoint expression on UCB NK cells compared to APB. However, the expression of TIGIT immune checkpoint is not indicative of NK cell exhaustion. 相似文献
93.
Katharine Edgerley Lisa Bryson Lucy Hanington Rachel Irving Shelagh Joss Anne Lampe Isabelle Maystadt Deborah Osio Ruth Richardson Miranda Split Francis H. Sansbury Ingrid Scurr Helen Stewart Alisdair McNeil Karen Low 《American journal of medical genetics. Part A》2023,191(5):1447-1458
To delineate further the clinical phenotype of Lamb–Shaffer Syndrome (LSS) 16 unpublished patients with heterozygous variation in SOX5 were identified either through the UK Decipher database or the study team was contacted by clinicians directly. Clinical phenotyping tables were completed for each patient by their responsible clinical geneticist. Photos and clinical features were compared to assess key phenotypes and genotype–phenotype correlation. We report 16 SOX5 variants all of which meet American College of Medical Genetics/Association for Clinical Genomic Science ACMG/ACGS criteria class IV or V. 7/16 have intragenic deletions of SOX5 and 9/16 have single nucleotide variants (including both truncating and missense variants). The cohort includes two sets of monozygotic twins and parental gonadal mosaicism is noted in one family. This cohort of 16 patients is compared with the 71 previously reported cases and corroborates previous phenotypic findings. As expected, the most common findings include global developmental delay with prominent speech delay, mild to moderate intellectual disability, behavioral abnormalities and sometimes subtle characteristic facial features. We expand in more detail on the behavioral phenotype and observe that there is a greater tendency toward lower growth parameters and microcephaly in patients with single nucleotide variants. This cohort provides further evidence of gonadal mosaicism in SOX5 variants; this should be considered when providing genetic counseling for couples with one affected child and an apparently de novo variant. 相似文献
94.
Klaus Pnicke Ingrid Heinroth-Hoffmann Karin Becker Otto-Erich Brodde 《British journal of pharmacology》1997,121(1):118-124
- Angiotensin II (AII) and the endothelins (ET) are known to be potent trophic stimuli in various cells including cardiomyocytes. In order to characterize further these effects we studied, in neonatal rat ventricular cardiomyocytes, the effects of several endothelin-receptor antagonists and the AT1-receptor antagonist losartan on AII- and endothelin-induced inositol phosphate (IP)-formation (assessed as accumulation of total [3H]-IPs in myo-[3H]-inositol prelabelled cells) and increase in rate of protein synthesis (assessed as [3H]-phenylalanine incorporation).
- Endothelin (10 pM–1 μM) concentration-dependently increased IP-formation (max. increase at 100 nM ET-1: 130±14% above basal, n=25) and [3H]-phenylalanine incorporation (max. increase at 1 μM: 52±4% above basal, n=16) with an order of potency: ET-1>>ET-3. Both effects were antagonized by the ETA/ETB-receptor antagonist bosentan and the ETA-receptor antagonist BQ-123, but not affected by the ETB-receptor antagonist IRL 1038 and the AT1-receptor antagonist losartan.
- Pretreatment of the cells with 500 ng ml−1 pertussis toxin (PTX) overnight that completely inactivated PTX-sensitive G-proteins did not attenuate but rather enhance ET-1-induced IP-formation. On the other hand, in PTX-pretreated cardiomyocytes ET-1-induced [3H]-phenylalanine incorporation was decreased by 39±5% (n=5).
- AII (1 nM–1 μM) concentration-dependently increased IP-formation (max. increase at 1 μM: 42±7% above basal, n=16) and [3H]-phenylalanine incorporation (max. increase at 1 μM: 29±2%, n=9). These effects were antagonized by losartan, but they were also antagonized by bosentan and BQ-123.
- In well-defined cultures of cardiomyocytes (not contaminated with non-myocyte cells) AII failed to increase [3H]-phenylalanine incorporation; addition of non-myocyte cells to the cardiomyocytes restored AII-induced increase in [3H]-phenylalanine incorporation.
- We conclude that, in rat neonatal ventricular cardiomyocytes, (a) the ET-1-induced increase in rate of protein synthesis (through ETA-receptor stimulation) involves at least two signalling pathways: one via a PTX-insensitive G-protein coupled to IP-formation, and the other one via a PTX-sensitive G-protein, and (b) the trophic effects of AII are brought about via local ET-1 secretion upon AT1-receptor stimulation in neonatal rat ventricular non-myocyte cells.
95.
D. Lang F. Hilger J. Binswanger G. Andelfinger W. Hartmann 《European journal of pediatrics》1995,154(5):340-345
Conclusion
Chemotherapy with anthracyclines even in low dosages, results in myocardial damage, which does not however, effect physical capacity over a long penod but which is revealed by reduced left ventricular wall thickness and myocardial mass. Functional effects include insufficient increase of SF, VCF and stroke volume during physical exercise. 相似文献96.
Swedish guidelines for early childhood education emphasize the importance of children's existential questions. The program encourages preschool to offer children different opportunities to work on questions like what it is to be, to live and die, grow old, about religion, beliefs, traditions, etc. at their level of maturity (Social-styrelsen, 1987). Our experience in teacher education and early childhood programs is, however, that this is an area in which many teachers have difficulties. In the present empirical study 13 teachers were interviewed to find outwhat they consider existential questions for their children to be, and whatstrategies or methods they have for dealing with these questions. Teachers' conceptions about the what and how aspects of existential questions are described in terms of their qualitative differences. Each teacher was then asked to keep a diary of the existential questions children raised during the following month. Differences between the teachers' conceptions, which showed hesitation, and the spontaneous approaches and active involvement that emerged in reality, as recorded in their own diaries, are discussed. 相似文献
97.
Øystein Bruserud Ingrid Nesthus Graham Pawelec 《Cancer chemotherapy and pharmacology》1995,37(1-2):70-78
The in vitro effect of the dextroisomer r-verapamil on blast cells derived from patients with acute myelogenous leukemia (AML) was studied. R-verapamil caused a dose-dependent inhibition of AML blast proliferation in the presence of stem-cell factor, leukemia inhibitory factor, interleukin 4, interleukin 6, and interleukin 10 when these cytokines were tested both alone and in different combinations. R-verapamil also inhibited the growth of clonogenic AML blast cells. The antiproliferative effect was not specific for AML blast cells, because r-verapamil also inhibited cytokine-dependent proliferation of blast cells derived from patients with acute lymphoblastic leukemia. The inhibitory effects of r-verapamil and anti-IL1 serum were additive, suggesting that the antiproliferative effect of r-verapamil does not depend solely on inhibition of IL1-mediated effects. Although r-verapamil inhibited spontaneous AML blast proliferation, for a majority of patients it caused only minimal, if any, inhibition of spontaneous cytokine secretion (IL1, IL1, TNF, IL6) by AML blast cells. Thus, although inhibition of IL1 effects may contribute in certain patients to the antiproliferative effect of r-verapamil, mechanisms other than IL1 inhibition seem to be more important in mediating the effects of r-verapamil.Abbreviations
ALL
Acute lymphocytic leukemia
-
AML
acute myelogenous leukemia
-
cpm
counts per minute
-
ELISA
enzyme-linked immunosorbent assay
-
G-CSF
granulocyte colony-stimulating factor
-
GM-CSF
granulocyte-macrophage colony-stimulating factor
-
IL
interleukin
-
IF
leukemia inhibitory factor
-
PBMC
peripheral blood mononuclear cells
-
RR
relative response
-
SCF
stem cell factor
-
TNF
tumor necrosis factor 相似文献
98.
Influence of a pre-operative enteral supplement on functional activities of peripheral leukocytes from patients with major surgery 总被引:2,自引:0,他引:2
Wachtler P Axel Hilger R König W Bauer KH Kemen M Köller M 《Clinical nutrition (Edinburgh, Scotland)》1995,14(5):275-282
Following severe trauma or major surgery patients develop functional alterations of host defense mechanisms which contribute an enhanced susceptibility towards microbial infections. Several studies have demonstrated that a specialized nutritional regimen may improve immune functions. We analyzed leukocyte functions from 40 patients undergoing major upper gastrointestinal surgery in a randomized placebo-controlled double-blind study. Patients were divided into two groups, one received 5 days pre-operatively an orally given experimental supplement enriched with omega-3-fatty acids, arginine, and ribonucleic acid (RNA), the other an isocaloric, control supplement. The experimental group generated significantly more leukotriene B(5) (LTB(5)) as compared to the control group. In contrast, the capacity to generate leukotriene B(4) (LTB(4)) as well as the synthesis of interleukin-8 (IL-8) was not significantly different in both groups. Additionally, lymphocyte/monocyte proliferation was analyzed and donor specific heterogeneities were observed; but no significant differences were found between the two nutritional regimens. 相似文献
99.
Cyclosporine is a powerful immunosuppressant with a narrow therapeutic window and considerable inter- and intrapatient variability.
The pre-dose trough concentration (Cmin) is commonly used for therapeutic drug monitoring. With the new microemulsion (Neoral), intrapatient variability was reduced.
However, the usefulness of Neoral Cmin was questioned. Firstly, because of the improved and more-rapid absorption, accidental intake before blood sampling has a
greater impact on Cmin than with classic cyclosporine. Secondly, Cmin may be low despite high drug exposure, due to rapid clearance in children. A full pharmacokinetic (PK) profile with determination
of the area under the curve (AUC) is expensive and cumbersome, and therefore a search for an abbreviated AUC began. Here,
we present a retrospective analysis of 84 PK profiles from 78 pediatric renal transplant recipients. By analysis of rejection
episodes and toxicity, we estimated a target AUC above 5,000 ng×h/ml in the early post-transplant period and 3,900 ng×h/ml
beyond 100 days. The abbreviated AUC using the 2- and 6-h concentrations (C2 and C6) and a simple estimate derived from the
3-h concentration (C3) were equally well correlated with the AUC. From our data, we recommend a target C3 at approximately
800 ng/ml early after transplantation and 450–550 ng/ml beyond 100 days.
Received: 28 January 1998 / Revised: 10 June 1998 / Accepted: 15 June 1998 相似文献
100.
Nonoperative Management of Primary Colorectal Cancer in Patients With Stage IV Disease 总被引:12,自引:0,他引:12
Scoggins CR Meszoely IM Blanke CD Beauchamp RD Leach SD 《Annals of surgical oncology》1999,6(7):651-657
Background: Traditional teaching maintains that patients with primary colorectal adenocarcinoma require timely resection to prevent bleeding, perforation, or obstruction. The true benefits of primary tumor resection remain undocumented for patients presenting with metastatic disease, however. We postulated that resection of primary colorectal tumors could be avoided safely in a select population of asymptomatic colorectal cancer patients presenting with incurable stage IV disease.Methods: A retrospective review of the Vanderbilt University Hospital tumor registry was performed for the years 1985 to 1997. During this period, 955 patients presented for management of primary colorectal cancer. From this group, all patients with stage IV disease at the time of diagnosis were identified. Patients who initially underwent resection of their primary lesion were included in the resection group; those who underwent initial nonoperative primary tumor management were included in the nonresection group. Data were obtained regarding age, extent of disease, nonsurgical therapy, tumor-specific complications, and palliative surgical procedures. Surgery-free survival and overall survival were analyzed using the Kaplan-Meier method. For patients with liver metastases, hepatic tumor burden was defined as either H1 (<25% parenchymal replacement), H2 (25% to 50%), or H3 (>50%) disease.Results: Sixty-six patients were included in the resection group, and 23 patients with intact asymptomatic primary colorectal lesions were included in the nonresection group. Among patients with hepatic metastases, most of the patients in both groups had H1 disease. Ten patients in the resection group and 3 patients in the nonresection group presented with exclusively extrahepatic metastases. In the nonresection group, primary therapy included chemotherapy in 13 patients, external beam radiation therapy in 1 patient, and combination chemoradiation in 9 patients. The median survival in the nonresection group was 16.6 months. The 2-year actuarial survival was 18%, and the surgery-free survival was 91.3%. Only 2 of 23 patients (8.7%) managed without resection eventually developed obstruction at the primary tumor site requiring emergent diversion. There were no episodes of tumor-related hemorrhage or perforation. For the resection group, the operative morbidity was 30.3%, and the perioperative mortality rate was 4.6%. The median survival in the resection group was 14.5 months (P = 0.59, log-rank test vs. nonresection group).Conclusions: Selected patients with asymptomatic primary colorectal tumors who present with incurable metastatic disease may safely avoid resection of their primary lesions, with an anticipated low rate of hemorrhage, perforation, or obstruction before death from systemic disease. No survival advantage is gained by resection of an asymptomatic primary lesion in the setting of incurable stage IV colorectal cancer. 相似文献