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61.
During their development, T lymphocytes make sequential cell fate choices: T rather than B lymphocytes, then TCRalphabeta or TCRgammadelta, CD4 or CD8, and Th1 or Th2 lineage. These fate choices require the initiation of new programs of gene expression, and once initiated, these programs must be faithfully propagated in a heritable manner from parental cells to their progeny. With the exception of the T cell receptor, these changes in gene expression occur without a change in information encoded directly in the DNA sequence. Rather, these heritable programs of gene expression are imposed, at least in part, epigenetically through changes in chromatin structure and DNA methylation, allowing T cells to tune the threshold for expression of specific genes. 相似文献
62.
Fertility preservation in gynecologic cancer 总被引:10,自引:0,他引:10
SUBJECT: Management of patients with gynecologic cancer can now often be tailored to the extent of the disease and preservation of child-bearing ability and/or sexual function may be possible for certain women with early invasive disease. METHOD: A better understanding of the tumor-biology, and the consideration of different clinicopathologic factors, that bear prognostic significance in therapeutic modalities, will allow more and more individualization of treatment. DISCUSSION: Management of young women with early gynecologic cancer should therefore be individualized with the risk of conservative therapy balanced against the dangers and advantages of more radical therapy. Experts in gynecologic oncology and infertility together with an informed patient and her family should make treatment decisions. OUTCOME: This article will review the conservative surgical management of early invasive cancers of the ovary, cervix and endometrium, in order to help preserve child-bearing capacity. In addition, management of gynecologic cancers diagnosed during pregnancy will also be discussed. 相似文献
63.
Ødegård RA Vatten LJ Nilsen ST Salvesen KA Vefring H Austgulen R 《Obstetrics and gynecology》2001,98(2):289-294
OBJECTIVE: To study the association between umbilical plasma levels of interleukin-6 (IL-6) in relation to fetal growth in subgroups of preeclampsia, and in control pregnancies. METHODS: Umbilical cord plasma was collected from 12,804 consecutive births. A total of 271 singleton cases of preeclampsia were identified, and classified as mild or severe, and as disease with early or late onset. As controls, 611 singleton pregnancies without preeclampsia were selected, and the ratio between observed and expected birth weight was used as a measure of fetal growth. In the analysis, we also included maternal smoking during pregnancy. Umbilical cord plasma IL-6 concentration was measured with an IL-6 bioassay. Comparing controls with subgroups of preeclampsia (severe and early onset), this study had a statistical power of 90% to detect a difference in cord IL-6 of 10 pg/mL. RESULTS: In severe preeclampsia, cord plasma IL-6 concentration was lower than among controls (P <.001), and there was a sharp decrease in cord plasma IL-6 with decreasing birth weight ratio (P trend <.001). By further dividing the preeclampsia group into early or late onset, the strong association between low IL-6 levels and low birth weight ratio appeared to be present mainly in early-onset disease. These results were not confounded by maternal smoking. CONCLUSION: Restricted fetal growth related to preeclampsia is associated with reduced umbilical cord plasma IL-6 concentration in cases with early-onset disease. In these cases, fetal growth restriction could be mediated by impaired trophoblast function. 相似文献
64.
65.
66.
ABSTRACT. Milt7eacute;nyi, M., Pohlandt, F., Bóka, G. and Kun, E. (2nd Department of Paediatrics, Semmelweis University, Medical School, Budapest, Hungary, and the Section of Neonatology, Centre of Paediatrics, University of Ulm, Federal Republic of Germany). Tubular proteinuria after perinatal hypoxia. Acta Paediatr Scand, 70:399, 1981.–Urinary total protein (UTP) and urinary protein pattern have been studied in 23 newborn infants with Apgar scores ±S3 at one minute or acidosis (pH ±7.15) on the first day. On the first and second day UTP excretion was increased in 13 out of 18 patients. At this time the excretion of low molecular weight microproteins (T-4 and T-5) was elevated in 12 patients without increased plasma urea concentration in any case. The increased excretion of the smallest microproteins T-4/T-5 is an early sign of an impaired tubular function. 相似文献
67.
V. V
TVIKA M. HANIKÝOV J. V
TVIKOV G. D. ROSS 《Clinical and experimental immunology》1999,115(2):229-235
Phagocyte and NK cell CR3 functions as both an adhesion molecule and an iC3b receptor mediating cytotoxic responses to microorganisms. Cytotoxic activation of iC3b receptor function requires ligation of both a CD11b I-domain site for iC3b and a lectin site located in the C-terminus of CD11b. Because tumours lack the CR3-binding polysaccharides of bacteria and fungi, iC3b-opsonized tumours do not stimulate CR3-dependent cytotoxicity. Previous studies showed that NK cells could be induced to kill iC3b-opsonized tumours with small soluble β-glucans that bound with high affinity to CR3, bypassing the absence of similar polysaccharides on tumour membranes. Because CR3 signalling requires several tyrosine phosphorylation events, it appeared possible that CR3-dependent killing of autologous tumour cells might be suppressed by NK cell inhibitory receptors for MHC class I (KIR and CD94/NKG2) whose action involves recruitment of SHP-1 and SHP-2 tyrosine phosphatases. In the current study, Epstein–Barr virus (EBV)-transformed B cells were used as targets following opsonization with iC3b. Soluble β-glucan primed CR3 for killing of iC3b-coated B cells, but autologous class I-bearing targets were 84% more resistant than class I-deficient Daudi cells. Blockade of target cell class I with a MoAb specific for a domain recognized by both KIR and CD94/NKG2 resulted in comparable killing of class I+ B cells. By contrast, another MoAb to class II had no effect on cytotoxicity. These data suggest that NK cell recognition of class I suppresses CR3/tyrosine kinase-dependent cytotoxicity in the same way as it suppresses cytotoxicity mediated by other tyrosine kinase-linked receptors such as FcγRIIIA (CD16). 相似文献
68.
Induction of B cell apoptosis by co-cross-linking CD23 and sIg involves aberrant regulation of c-myc and is inhibited by bcl-2 总被引:2,自引:0,他引:2
Campbell KA; Studer EJ; Kilmon MA; Lees A; Finkelman F; Conrad DH 《International immunology》1997,9(8):1131-1140
A novel system to study the effects of co-cross-linking CD23/FceRII and sIg
on murine B lymphocytes utilizes a highly multivalent form of anti- Ig
prepared by covalently linking anti-Ig antibodies to a DNP-dextran
backbone. CD23-sIg co-cross-linking is accomplished by the addition of
DNP-specific monoclonal IgE. Previous studies demonstrated that co-
cross-linking CD23 and sIg significantly inhibited mouse B cell
proliferation, especially at high doses of the multivalent anti-Ig.
Interestingly, examination of early activation signals reveals no
difference in B cells subjected to co-cross-linking conditions as compared
to B cells activated with anti-Ig alone. Total cellular protein tyrosine
phosphorylation levels are unchanged by co-cross- linking. Analysis of B
cell mRNA reveals that co-cross-linking the receptors does not alter the
expression levels of ornithine decarboxylase 8 h after stimulation as
compared to the controls. In contrast, levels of the proto-oncogene c-myc
were significantly elevated 1 h after inducing B cell activation under
co-cross-linking conditions. However, it remains unclear whether this
aberrant c-myc regulation plays any role in inducing apoptosis. In
addition, on day 3 after stimulation, the co-cross-linking of CD23 and sIg
resulted in the formation of apoptotic B cells, determined by both
photomicroscopy of the B cell cultures and FACS analysis of B cell nuclei.
B cells obtained from bcl-2 transgenic mice proliferated as well as
controls, and failed to undergo apoptosis when CD23 and sIg were
co-cross-linked on their surface. These studies indicate that
co-cross-linking of CD23 with B cell sIg inhibits B cell proliferation by a
mechanism that is distinct from that seen by co-cross-linking of the Fc
gamma RII and sIg. In addition, these results suggest a means by which
antigen- specific IgE can down-regulate additional B cell activation and
IgE synthesis.
相似文献
69.
Molecular characterization of human factor XSan Antonio 总被引:1,自引:0,他引:1
Enzymatic amplification technique was used to isolate all eight exons and sequences around the splice junctions, putative promoter, and polyadenylation sites of human factor X DNA from a patient with factor X deficiency. Two genetic changes in factor X have been observed in this patient. The patient is most likely a compound heterozygote since there is only 14% activity associated with factor X. A point mutation that resulted in the substitution of cysteine (TGC) for arginine (CGC) at amino acid 366 was found in exon VIII of one allele of the factor X gene. This mutation, which occurs in the catalytic domain, can affect the formation of a disulfide bridge and thus could result in a reduction in factor X activity. Sequencing all the regions revealed a second mutation: a deletion of one nucleotide (TCCT to TCT) in exon VII that would cause a frame shift at amino acid 272 followed by termination. We have also shown that the point mutation in exon VIII creates an ApaL1 restriction site and destroys the HinP1 site. Enzymatic DNA amplification followed by restriction digestion provides a quick, reliable, and sensitive method for carrier detection and antenatal diagnosis in affected kindreds. This is the first characterization of factor X deficiency at the molecular level. We propose to name this mutation Factor XSan Antonio. 相似文献
70.
A model of corrective gene transfer in X-linked ichthyosis 总被引:5,自引:0,他引:5
Freiberg RA; Choate KA; Deng H; Alperin ES; Shapiro LJ; Khavari PA 《Human molecular genetics》1997,6(6):927-933
Single gene recessive genetic skin disorders offer attractive prototypes
for the development of therapeutic cutaneous gene delivery. We have
utilized X-linked ichthyosis (XLI), characterized by loss of function of
the steroid sulfatase arylsulfatase C (STS), to develop a model of
corrective gene delivery to human skin in vivo. A new retroviral expression
vector was produced and utilized to effect STS gene transfer to primary
keratinocytes from XLI patients. Transduction was associated with
restoration of full-length STS protein expression as well as steroid
sulfatase enzymatic activity in proportion to the number of proviral
integrations in XLI cells. Transduced and uncorrected XLI keratinocytes,
along with normal controls, were then grafted onto immunodeficient mice to
regenerate full thickness human epidermis. Unmodified XLI keratinocytes
regenerated a hyperkeratotic epidermis lacking STS expression with
defective skin barrier function, effectively recapitulating the human
disease in vivo. Transduced XLI keratinocytes from the same patients,
however, regenerated epidermis histologically indistinguishable from that
formed by keratinocytes from patients with normal skin. Transduced XLI
epidermis demonstrated STS expression in vivo by immunostaining as well as
a normalization of histologic appearance at 5 weeks post-grafting. In
addition, transduced XLI epidermis demonstrated a return of barrier
function parameters to normal. These findings demonstrate corrective gene
delivery in human XLI patient skin tissue at both molecular and functional
levels and provide a model of human cutaneous gene therapy.
相似文献