Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is strong evidence that cytokines and growth factors play an important role as local mediators of the actions of steroids on the endometrium to prepare it for implantation. These factors have also been shown to act in both an autocrine and paracrine manner to regulate the development of preimplantation embryos in several species. Attempts to define the function of each cytokine have involved receptor localization, establishment of the mode of control by steroid hormones, and functional assays in vivo and in vitro. However, because of the complex and redundant nature of cytokine networks, defining which of this plethora of factors plays a critical role in implantation has proved difficult. Although the development of preimplantation embryos can be influenced directly by cytokines, the in vitro culture of embryos from several species in defined media indicates that exogenous cytokines are not essential for development to the blastocyst stage. Nonetheless, supplementation of media with growth factors may prove valuable in overcoming the detrimental effects of embryo culture in vitro, which is widely used in assisted reproduction techniques in humans and domestic species. The creation of mouse strains in which specific genes for growth factors or adhesion molecules are deleted has also proved important in defining factors essential in implantation, as well as those that play a less significant role. Mice unable to express leukaemia inhibitory factor in the endometrium fail to support implantation, indicating a critical role for this protein in producing a receptive endometrium. Conversely, mouse embryos of the CF-1 strain, which lack the receptor for epidermal growth factor, fail to attach, indicating that this receptor is necessary for producing an implantation competent embryo. It is likely that abnormal expression of such receptors or their ligands in the endometrium underlies some forms of human infertility. Examining the actions of these factors in the endometrium will allow dissection of the molecular basis of embryo attachment and implantation.
 ...
PMID:Cytokines and implantation. 950 89

Leukaemia inhibitory factor (LIF) is a pleiotrophic cytokine required for blastocyst implantation in mice. Uterine expression of LIF and that of its receptors has been demonstrated in a number of mammalian species indicating that LIF may have widespread importance in the establishment of pregnancy. The variations in the reaction of the uterus in preparation for and during implantation are considerable between species and understanding the differences and similarities assists in the interpretation of how this cytokine functions. Recent studies suggest that reduced endometrial LIF contributes to human infertility. Studies also demonstrate a potential role in placentation and fetal development. Thus, LIF has become an important cytokine warranting further investigation in the human. It is anticipated that when the mechanisms underlying normal embryonic and endometrial development are elucidated, fertility and infertility will be more precisely understood and hence able to be effectively controlled.
 ...
PMID:Review: The role of leukaemia inhibitory factor in the establishment of pregnancy. 992 86

Internal genitalia and uterine blood flow were assessed by ultrasound in 12 females 4.0-10.9 years after total body irradiation and allogeneic bone marrow transplantation for childhood leukaemia or lymphoma. Median age of the participants was 12.7 years (range 6.1-17.6) at bone marrow transplantation and 21.5 years (11.6-25.6) at the follow-up study. At follow-up all had entered puberty and 11/12 females had experienced the menarche. Eight females received sex steroid replacement therapy, three had spontaneous pubertal development and one woman experienced symptoms of estrogen deficiency. Median uterine and ovarian volumes were significantly reduced to -2.6 standard deviation scores (SDS) (-6.3 to -0.6), P = 0.002, and -2.6 SDS (-4.8 to -0.5), P = 0.002, respectively, compared with normal controls. Follicles were only detectable in two individuals. Uterine blood flow was impaired, as a systolic blood flow could be measured in 6/9 individuals, and a diastolic blood flow in 1/9 females. Our results indicate that the prescribed dosage of hormone replacement therapy, which was sufficient to induce bleeding and suppress other stigmata of premature menopause, was inadequate to generate normal uterine growth. In order to achieve uterine growth higher doses of hormone replacement therapy may be required. Our results confirm pelvic ultrasound as a reliable tool for investigation of internal female genitalia; however, in an infertility setting further tests are indicated.
 ...
PMID:Ultrasound B-mode changes in the uterus and ovaries and Doppler changes in the uterus after total body irradiation and allogeneic bone marrow transplantation in childhood. 1008 57

The glycoprotein leukaemia inhibitory factor (LIF) is produced by the endometrium and is involved in the control of implantation. In women with unexplained infertility reduced uterine concentrations of LIF have been reported. Studies with mice lacking a functional LIF gene have shown that the LIF protein is essential for implantation of the embryo. We have developed a method for screening of gene mutations in the coding region and critical regulatory regions of the LIF gene. Thus we could screen nulligravid infertile women (n = 74), fertile controls (n = 75) and as a second unrelated control group, neurological patients (n = 131) for LIF gene mutations. In infertile women, three heterozygous point mutations have been identified: one in close proximity to the start codon of exon 1 and two mutations in exon 3. These correspond to regions of the LIF protein which are thought to be highly important for interaction with the LIF receptor and thus lead to reduced biological activity of the LIF protein. Only one point mutation/polymorphism in the non-coding region between exon 2 and 3 was found in the control groups. Our results suggest that heterozygosity for a LIF gene mutation could give rise to decreased availability or biological activity of LIF in the uterus and cause implantation failure. Thus the mutations identified in our study could be responsible for infertility in a subgroup of nulligravid women.
 ...
PMID:Leukaemia inhibitory factor gene mutations in infertile women. 1034 Oct 7

In bovine oviduct cells 17beta-oestradiol can induce the synthesis of leukaemia inhibitory factor (LIF), a glycoprotein essential for embryo implantation. Therefore substances which are structurally similar to 17beta-oestradiol and possess oestrogenic activity may also modulate LIF synthesis and influence the reproductive process. We used primary cultures of bovine and human oviduct cells (epithelial cells:fibroblasts 1:1) to compare the effects of 17beta-oestradiol, phyto-oestrogens (genistein, biochanin A, daidzein, formononetin, and equol) and xeno-oestrogens [polychlorinated biphenyls (PCB): trichlorobiphenyl, 4-hydroxy-trichlorobiphenyl and 4-hydroxy-dichlorobiphenyl] on LIF synthesis. Immunoreactive LIF-enzyme-linked immunosorbent assay was used to determine the concentration of LIF in the culture medium. Similar to 17beta-oestradiol, genistein (0.02-2 micromol/l) induced LIF synthesis in bovine oviduct cells in a concentration-dependent manner. Equol, biochanin A and daidzein (2 micromol/l), 4-hydroxy-trichlorobiphenyl and 4-hydroxy-dichlorobiphenyl (0.01-10 micromol/l) but not formononetin (2 micromol/l) also induced LIF synthesis in bovine cells. Phyto-oestrogens and xeno-oestrogens also induced LIF synthesis in human oviduct cells (P < 0.05). The stimulatory effects of PCB, phyto-oestrogens and 17beta-oestradiol were blocked by ICI 182,780 (1 micromol/l). Moreover, 17beta-oestradiol, 4-hydroxy-trichlorobiphenyl, 4-hydroxy-dichlorobiphenyl, genistein, tamoxifen and ICI 182,780 displaced [(3)H]17beta-oestradiol from cytosolic oestrogen receptors in bovine oviduct cells. These results suggest that phyto-oestrogens and PCB mimic the effects of oestradiol in inducing LIF synthesis by bovine and human oviduct cells and that these stimulatory effects are oestrogen receptor-mediated. Environmental oestrogens act as endocrine modulators/disrupters and may induce deleterious effects on the reproductive process by influencing LIF synthesis in a non-cyclic fashion leading to tubal infertility.
 ...
PMID:Xeno-oestrogens and phyto-oestrogens induce the synthesis of leukaemia inhibitory factor by human and bovine oviduct cells. 1050 16

A case is presented of a young adult male diagnosed with acute myeloid leukaemia who was treated with busulphan and cyclophosphamide, but not total body irradiation, with subsequent bone marrow transplantation. After surviving for 5 years, he and his wife experienced a period of infertility. Interestingly, the problem was found to be with the female partner and the man's sperm evaluation seemed normal. A successful pregnancy ensued following the surgical removal of a large endometrioma and treating a luteal phase deficiency. Though this may be the fifth case of proven parentage in cases of bone marrow conditioning and bone marrow transplantation in a male for control of leukaemia, we believe it is the first documented case showing a normal semen analysis despite treatment. Further studies are needed to see if chemical conditioning with busulphan and cyclophosphamide preserve the chances of sperm production better than total body irradiation.
 ...
PMID:Recovery of spermatogenesis and successful conception after bone marrow transplant for acute leukaemia: case report. 1061 Nov 93

The majority of newly diagnosed patients are expected to survive Hodgkin's disease because of effective therapies established during past 30 years. Long-term observations from large populations of treated patients have disclosed a variety of late effects of the disease and its therapy have contributed morbidity and excess mortality to Hodgkin's disease survivors. Secondary cancers have continued to accrue, and the risk relative to the general population has increased to 6.4 (95% confidence intervals: 5.5 to 7.3) in updated experience at Stanford University. Risks are significantly elevated for leukemia (primarily after chemotherapy regimens containing alkylating agents); non-Hodgkin's lymphoma; and tumors of the lung, breast, soft tissues, bone, stomach, pancreas, salivary gland, thyroid, and cutaneous melanoma. Early cardiovascular disease has also been observed and numerically exceeds second cancers as a cause of death in patients with early stage Hodgkin's disease (49 v 47 cases). Pulmonary dysfunction, thyroid dysfunction, infertility, psychosocial changes, gastrointestinal problems, soft-tissue changes, alterations in immunity, and risks for infection have also affected some treated patients. As these problems have been recognized, treatment approaches have been modified over the last 10 to 15 years, and early data suggest a decrease in some treatment sequellae.
 ...
PMID:Long-Term Complications of Treatment and Causes of Mortality After Hodgkin's Disease. 1071 80

Implantation is a process that involves development, attachment and invasion of the blastocyst into the endometrium. Successful implantation requires appropriate communication between the embryo and maternal endometrium. There is evidence to suggest that cytokines produced by the maternal endometrium and the developing embryo play a crucial role in this signalling process. Although numerous cytokine-receptor pairs are expressed by the maternal endometrium and the embryo during implantation, functional knowledge of these cytokines is limited. Compelling data demonstrating a functional role for cytokines in implantation comes from studies using specific cytokine and cytokine receptor knockout mice. There are limited similar data for human implantation, but clinical correlative data and studies using in vitro models indicate that cytokines may have an important functional role in this process. Cytokines that appear to have a functional role in mammalian implantation include leukaemia inhibitory factor, interleukin 1, hepatocyte growth factor, stem cell factor, macrophage colony-stimulating factor and insulin-like growth factors. As implantation failure is a significant cause of natural and in vitro fertilization pregnancy failure, a better understanding of the functional role of these cytokine-receptor pairs is important for improving the diagnosis and treatment of infertility.
 ...
PMID:Cytokines in implantation. 1088 32

Combination chemotherapy, often in conjunction with surgery and external radiotherapy, is utilized in most children with tumors of the genitourinary tract. These chemotherapeutic agents are capable of causing a variety of delayed toxicities. Common late complications include cardiotoxicity associated with prior exposure to an anthracycline, pulmonary dysfunction, infertility in males due to prior therapy with alkylating agents, and secondary leukemia in individuals treated with epipodophyllotoxins.
 ...
PMID:The long-term complications of chemotherapy in childhood genitourinary tumors. 1098 55

Cryopreservation of testicular tissue might benefit prepubertal boys who have to undergo chemotherapy or radiotherapy. Cryopreservation of testicular tissue is feasible. Live offspring have been born to mice, but not other species after transplantation of testicular cells. Spermatogenesis in vitro would be an excellent option for boys with leukaemia, but the method is not feasible for the time being. Cryopreservation of biopsied testicular tissue for intracytoplasmic sperm injection (ICSI) is a feasible option for infertility treatment of azoospermic men. Testicular sperm can be frozen as cell suspension, or within a piece of testicular tissue. Both methods result in pregnancies. Testicular needle biopsy is a simple method to obtain tissue for histological diagnosis, for ICSI and for cryopreservation for use in the future. Testicular sperm should be cryopreserved whenever a testicular biopsy is carried out.
 ...
PMID:Cryopreservation of testicular tissue. 1115 42


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>