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Charles B. Pratt Edwin C. Douglass William H. Meyer F. Ann Hayes Marc E. Horowitz Elizabeth I. Thompson Loraine Avery 《Investigational new drugs》1989,7(2-3):209-211
Summary 4 -Deoxydoxorubicin was given to 15 patients with drug-resistant pediatric malignant solid tumors with the objectives of determining the maximum tolerated dosage and dose-limiting toxicity. Maximum tolerated dosage was 36 mg/m2 given IV once every 3 weeks. Dose limiting toxicity was myelosuppression, which was severe and prolonged. Therapeutic benefits were not observed for these patients. 相似文献
25.
Pete Kaiser Tuang Yeow Poh Lisa Rothwell Stuart Avery Sucharitha Balu Uday S Pathania Simon Hughes Marianne Goodchild Shaun Morrell Michael Watson Nat Bumstead Jim Kaufman John R Young 《Journal of interferon & cytokine research》2005,25(8):467-484
As most mechanisms of adaptive immunity evolved during the divergence of vertebrates, the immune systems of extant vertebrates represent different successful variations on the themes initiated in their earliest common ancestors. The genes involved in elaborating these mechanisms have been subject to exceptional selective pressures in an arms race with highly adaptable pathogens, resulting in highly divergent sequences of orthologous genes and the gain and loss of members of gene families as different species find different solutions to the challenge of infection. Consequently, it has been difficult to transfer to the chicken detailed knowledge of the molecular mechanisms of the mammalian immune system and, thus, to enhance the already significant contribution of chickens toward understanding the evolution of immunity. The availability of the chicken genome sequence provides the opportunity to resolve outstanding questions concerning which molecular components of the immune system are shared between mammals and birds and which represent their unique evolutionary solutions. We have integrated genome data with existing knowledge to make a new comparative census of members of cytokine and chemokine gene families, distinguishing the core set of molecules likely to be common to all higher vertebrates from those particular to these 300 million-year-old lineages. Some differences can be explained by the different architectures of the mammalian and avian immune systems. Chickens lack lymph nodes and also the genes for the lymphotoxins and lymphotoxin receptors. The lack of functional eosinophils correlates with the absence of the eotaxin genes and our previously reported observation that interleukin- 5 (IL-5) is a pseudogene. To summarize, in the chicken genome, we can identify the genes for 23 ILs, 8 type I interferons (IFNs), IFN-gamma, 1 colony-stimulating factor (GM-CSF), 2 of the 3 known transforming growth factors (TGFs), 24 chemokines (1 XCL, 14 CCL, 8 CXCL, and 1 CX3CL), and 10 tumor necrosis factor superfamily (TNFSF) members. Receptor genes present in the genome suggest the likely presence of 2 other ILs, 1 other CSF, and 2 other TNFSF members. 相似文献
26.
Determination of optimal cryoprotectants and procedures for their addition and removal from human spermatozoa 总被引:9,自引:7,他引:9
The objective was to test the hypothesis that the optimal cryoprotective
agent for cryopreservation of human spermatozoa would be a solute for which
cells have the highest plasma membrane permeability, resulting in the least
amount of volume excursion during its addition and removal. To test this
hypothesis, theoretical simulations were performed using membrane
permeability coefficients to predict optimal procedures for the addition
and removal of a cryoprotectant. Simulations were performed using data from
four different cryoprotectants: (i) glycerol, (ii) dimethyl sulphoxide,
(iii) propylene glycol and (iv) ethylene glycol. Thermodynamic formulations
were applied to determine approaches for the addition and removal of 1 M
and 2 M final concentrations of cryoprotectant, allowing the spermatozoa to
maintain a cell volume within their osmotic tolerance limits. Based on
these data, ethylene glycol was predicted to be optimal for minimizing
volume excursions among the solutes evaluated. These predictions were then
experimentally tested using glycerol as the control cryoprotectant and
ethylene glycol as the experimental cryoprotectant. The results indicate
that there was a higher (P < 0.05) recovery of motile spermatozoa after
cryopreservation when using 1 M ethylene glycol than with 1 M glycerol,
supporting the hypothesis that use of the cryoprotectant for which the cell
has the highest permeability will result in higher cell survival.
相似文献
27.
Donor insemination: Dutch parents' opinions about confidentiality and donor anonymity and the emotional adjustment of their children 总被引:1,自引:4,他引:1
Brewaeys A; Golombok S; Naaktgeboren N; de Bruyn JK; van Hall EV 《Human reproduction (Oxford, England)》1997,12(7):1591-1597
Results from a comparative study investigating 38 donor insemination (DI)
Dutch families with 4-8 year old children are presented. The aims of this
study were to investigate parents' opinions on the issues of
confidentiality and donor anonymity, to assess the emotional development of
the children, and to examine in DI families the association between secrecy
with regard to the use of a donor and the emotional adjustment of the
children. The DI families were compared to families with a child conceived
by in-vitro fertilization (IVF) and to families with a naturally conceived
child. Secrecy appeared to be associated with DI and not with IVF: 74% of
the DI parents intended not to inform the child about the way in which
she/he was conceived, whereas none of the IVF parents intended to keep the
secret. Only one set of DI parents and two sets of IVF parents had actually
told the child. As to donor anonymity, a spread of opinions appeared among
DI parents; 57% preferred an anonymous donor, 31% would have liked non-
identifying information about the donor, 9% preferred the donor's identity
to be registered and 3% remained unsure. Parents' major concern was to know
more about the medical/genetic background of the donor. Mothers and fathers
in the DI families differed in their opinions concerning the issues of
confidentiality and donor anonymity: fathers, more often than mothers, were
secretive with regard to the use of a donor and husbands, more often than
their wives, were in favour of donor anonymity. With regard to the
emotional development of the children, more emotional/behavioural problems
were revealed among DI children than among children who were naturally
conceived. No association was found between secrecy and the
emotional/behavioural adjustment of the children.
相似文献
28.
Antigen-presenting cells (APC) play a key role in orchestrating immune responses. T-cell proliferative responses are inhibited during the erythrocyte stages of malaria infection, and a number of studies have suggested that APC are responsible for this phenomenon. In the present studies we examine individual components of the T-cell-activating function of APC: expression of costimulatory and major histocompatibility complex (MHC) class II proteins, the ability to process and present antigen to T cells, and the ability to support cytokine production. We find that during the acute phases of Plasmodium yoelii erythrocyte stage infection, APC upregulate the expression of class II MHC and CD80, maintain expression of CD86, process and present antigen, and support gamma interferon production. However the CD11b(+) subpopulation produces a soluble factor or factors that specifically inhibit interleukin-2 (IL-2) production by responding CD4 T cells. This factor is distinct from prostaglandin E(2), NO, or transforming growth factor beta. The data suggest that IL-2 suppression observed during malaria infection is not due to functional defects of APC but is triggered by production of a factor(s) that actively suppresses production of IL-2 by T cells. 相似文献
29.
Fibrin sealant: clinical use and the development of the University of Virginia Tissue Adhesive Center 总被引:3,自引:0,他引:3
Mintz PD Mayers L Avery N Flanagan HL Burks SG Spotnitz WD 《Annals of clinical and laboratory science》2001,31(1):108-118
The utilization of fibrin sealants to augment hemostasis, seal tissues, and facilitate targeted delivery of drugs is increasing. In 1985, a hospital-based program was established to provide autologous and allogeneic cryoprecipitate that serves as a fibrin sealant when combined with bovine thrombin. To date, more than 4,000 patients have been treated with this product at our institution, with an efficacy rate greater than 90%. Collaboration among surgical services and the blood bank fostered multispecialty expertise with this product that led, in 1997, to the establishment of the University of Virginia Tissue Adhesive Center. The Tissue Adhesive Center is a multidisciplinary center whose physician director and nursing and administrative support staff facilitate basic research, laboratory investigation, and preclinical and clinical trials with collaborators throughout the university. The Tissue Adhesive Center also provides educational programs and clinical consultation, and tracks and participates in peer review of sealant use. The licensure of a commercially produced, virally inactivated, pooled-plasma fibrin sealant in May 1998 provided an alternative source of adhesive. Utilization of the commercial product surpassed use of the blood bank product in April 1999. At present, use of the commercial product is approximately 3 times that of the blood bank-produced sealant. This report reviews the clinical uses of fibrin sealant, its regulatory history, the production of fibrin sealants, the evolution of a blood bank fibrin sealant program, the development of the Tissue Adhesive Center, and the utilization of commercial and blood bank-produced sealant at our university hospital. 相似文献
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