Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0085110 (SCID)
 11,041 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Investigation of the process of Peyer's patch (PP) formation has been hampered by difficulties in identifying its initial step in the embryo. In this study, we overcame this problem by means of whole-mount immunohistochemistry using mAb against the molecules which were expressed in the cells accumulated at the site of PP development. This method was sensitive enough to distinguish a minute cell cluster in the developing gastrointestinal tract. We analyzed the time course of the expression of various surface markers and found that PP formation proceeds through three successive steps. The first is the appearance of a VCAM-1+ cell cluster at 15.5 days postcoitus (d.p.c.). Histological examination of the VCAM-1+ clusters suggested that VCAM-1+ cells represent a stromal component. The second step is characterized by the accumulation of round cells expressing la, IL-7R or CD4 at 17.5 d.p.c. Lymphocytes expressing CD3 or B220 were detected only in the final step which started at 18.5 d.p.c. Using any of these markers, the aggregation was initially detected on the upper jejunum and it extended to the colon as the number of clusters increased. At the neonatal stage, the number reached up to eight or nine, irrespective of the antibodies used for the detection. In the aly/aly mutant mouse, where no lymph nodes or PP are found in the adult, none of these three steps was detected. On the other hand, in the SCID mouse that is defective in the formation of mature lymphocytes, the first and second step proceeded, whereas the third step was undetectable. These findings suggest that the progression of each step is indeed regulated by different mechanisms.
 ...
PMID:Three distinctive steps in Peyer's patch formation of murine embryo. 913 10

A chimeric severe combined immunodeficient mouse engrafted with human peripheral blood (hu-PBL-SCID) model has been developed to test anti-T-cell monoclonal antibody (mAb) effects on systemic symptoms of the host and the survival of human skin grafts. To obtain consistent engraftment without lethal acute graft-versus-host disease (GVHD), SCID mice were pretreated with a combination of total body irradiation (2.5 Gy, day 0) and anti-asialo GM1 (anti-mouse natural killer cell) antiserum (50 micrograms i.p., day 3) before the intraperitoneal injection of 40-50 X 10(6) human PBL on day 4. With this protocol, the engraftment rate was 82% with 5-98% human CD45-positive cells in the peripheral blood. Mortality at 30 days was 0% in the mice bearing 5-50% human cells compared with 70% in those with more than 50%. Using hu-PBL-SCID mice with 5-50% human cells in their peripheral blood, we demonstrated the following results: 1) Human T cells isolated from these mice proliferated in response to immobilized OKT3 stimulation in vitro. 2) Hu-PBL-SCID mice but not normal SCID mice were able to reject human skin grafts in vivo 16-21 days after grafting. 3) Both OKT3 (anti-human CD3 mAb) and T10B9 (anti-human alpha beta T-cell receptor mAb) treatment prevented human skin graft rejection in hu-PBL-SCID mice. 4) OKT3 but not T10B9 induced first dose reactions characterized by hypothermia and hypoactivity which were consistently observed within 90 min of intravenous injection into hu-PBL-SCID mice. 5) Human cytokines were detected in the serum of the hu-PBL-SCID mice treated with anti-T-cell mAbs. The close similarity of these responses to human clinical mAb immunosuppressive therapy suggests that the hu-PBL-SCID mouse model may be an excellent tool for investigating the immunosuppression, side effects, and mechanism of action of agents that are specific for human and higher apes and not reactive with lower animals.
 ...
PMID:A model of human anti-T-cell monoclonal antibody therapy in SCID mice engrafted with human peripheral blood lymphocytes. 936 54

Ileocecal junction (ICJ) and proximal intestine (PI) fragments from CD45(323-) allovariant fetal pigs were grafted subcutaneously into SCID mice. The xenografts were examined 8-12 weeks later using two-color immunohistology and the ICJ, but not PI, xenografts were found to contain three types of vessels. The first (the majority) was lined with mouse endothelium (mAb 9F1+), the second was lined with pig endothelium, and the third was chimeric. The ICJ vessels were specifically lined with mouse endothelium expressing MAdCAM-1, the mucosal addressin. Vessels lined with pig endothelium alone did not express the MAdCAM-1 epitopes. Radiolabeled allovariant pig peripheral blood lymphocytes (PBL) were introduced i.v. into the xenografted SCID mice, and entry into xenografts studied. Pig PBL were occasionally seen in MECA-367+ vessel walls after 4 h and within the ICJ but not PI xenografts after 24 h. This entry was specifically blocked by coinjection of the anti-MAdCAM-1 mAb MECA-367. The results demonstrate reendothelialization of xenografts by host endothelium that expresses its own addressin and is functional for xenogenic PBL.
 ...
PMID:Pig lymphocytes utilise mouse MAdCAM-1 to enter fetal gut xenografts in SCID mice. 942 8

We investigated the role of IL-7 receptor alpha (IL-7Ralpha) signal in the formation of Peyer's patch (PP) anlage. Although pan-lymphopenia is a common phenotype of rag2-/- and il7ralpha-/- mice, a close inspection revealed nodules corresponding to PP in the adult rag2-/- but not in the il7ralpha-/- mouse. In our previous study, three histologically distinct steps in the formation of PP were identified. The first is the appearance of VCAM-1 + spots in the intestine, which probably represents an initial stage of the formation of the PP anlage. Accumulation of cells bearing IL-7Ralpha, CD4 or Ia in this region then follows and eventually entry of mature lymphocytes expressing CD3 or B220 occurs just before birth. Based on this criterion, we next investigated which of these events is defective in mice with severe combined immunodeficiency. Formation of VCAM-1 + spots and cluster formation of IL-7Ralpha+ cells proceed normally in the rag2-/- mouse which completely lacks mature lymphocytes. In contrast, no VCAM-1+ spots were detected in the embryonic nor neonatal il7ralpha-/- mice, suggesting that IL-7Ralpha signal is involved in the early phase of PP anlage formation. The same defect was found in the jak3-/- mouse. In addition to the appearance of VCAM1+ spots, the clustering of IL-7Ralpha+ cells was absent in the jak3-/- mouse, though IL-7Ralpha+ cells are found to scatter over the intestine. These results indicate that IL-7Ralpha is an essential signal for an early step of PP anlage formation, without which the subsequent processes cannot be initiated.
 ...
PMID:Essential role of IL-7 receptor alpha in the formation of Peyer's patch anlage. 948 50

In vivo expansion and multilineage outgrowth of human immature hematopoietic cell subsets from umbilical cord blood (UCB) were studied by transplantation into hereditary immunodeficient (SCID) mice. The mice were preconditioned with Cl2MDP-liposomes to deplete macrophages and 3.5 Gy total body irradiation (TBI). As measured by immunophenotyping, this procedure resulted in high levels of human CD45(+) cells in SCID mouse bone marrow (BM) 5 weeks after transplantation, similar to the levels of human cells observed in NOD/SCID mice preconditioned with TBI. Grafts containing approximately 10(7) unfractionated cells, approximately 10(5) purified CD34+ cells, or 5 x 10(3) purified CD34+CD38- cells yielded equivalent numbers of human CD45+ cells in the SCID mouse BM, which contained human CD34+ cells, monocytes, granulocytes, erythroid cells, and B lymphocytes at different stages of maturation. Low numbers of human GpA+ erythroid cells and CD41+ platelets were observed in the peripheral blood of engrafted mice. CD34+CD38+ cells (5 x 10(4)/mouse) failed to engraft, whereas CD34- cells (10(7)/mouse) displayed only low levels of chimerism, mainly due to mature T lymphocytes. Transplantation of graded numbers of UCB cells resulted in a proportional increase of the percentages of CD45+ and CD34+ cells produced in SCID mouse BM. In contrast, the number of immature, CD34+CD38- cells produced in vivo showed a second-order relation to CD34+ graft size, and mice engrafted with purified CD34+CD38- grafts produced 10-fold fewer CD34+ cells without detectable CD34+CD38- cells than mice transplanted with equivalent numbers of unfractionated or purified CD34+ cells. These results indicate that SCID repopulating CD34+CD38- cells require CD34+CD38+ accessory cell support for survival and expansion of immature cells, but not for production of mature multilineage progeny in SCID mouse BM. These accessory cells are present in the purified, nonrepopulating CD34+CD38+ subset as was directly proven by the ability of this fraction to restore the maintenance and expansion of immature CD34+CD38- cells in vivo when cotransplanted with purified CD34+CD38- grafts. The possibility to distinguish between maintenance and outgrowth of immature repopulating cells in SCID mice will facilitate further studies on the regulatory functions of accessory cells, growth factors, and other stimuli. Such information will be essential to design efficient stem cell expansion procedures for clinical use.
 ...
PMID:Transplantation of human umbilical cord blood cells in macrophage-depleted SCID mice: evidence for accessory cell involvement in expansion of immature CD34+CD38- cells. 949 Jun 79

We hypothesized that human hematopoietic cells displaying a CD34+, kit-, rhodamine123(low) phenotype would be highly enriched for cells with stem-like properties. To test this hypothesis, we employed fluorescence activated cell sorting (FACS) to isolate cells with this phenotype from normal light density marrow mononuclear cells (MNC). CD34+, kit+, rhodamine123(low) cells comprised from 0.05-0.01% of the total MNC population. They were small, had scant cytoplasm, and contained nuclei with dense, hyperchromatic chromatin and inconspicuous nucleoli. Additional immunophenotyping revealed that these cells were CD33-, CD38-, CD20-, and glycophorin A-. When plated in semisolid cultures containing optimal concentrations of IL-3, GM-CSF, KL, EPO, IL-6, and IL-1 these cells did not form colonies. However, when cultured over irradiated stromal cells, cobblestone areas were observed to form after 3 weeks, and harvested cells were able to initiate long-term cultures. To further demonstrate that these cells were indeed stem like, we also tested their ability to engraft and mature in immunocompromised (SCID) mice. Irradiated (400 cGy) SCID mice were transplanted with 2 x 10(3) candidate stem cells which were then injected with recombinant human growth factors every other day. Two months post-transplant the animals were sacrificed. PCR and FACS analysis of marrow and spleen cell samples revealed the presence of cells expressing human CD45 consistent with engraftment of human stem cells and the establishment of murine-human chimerism. Moreover, MNC isolated from transplanted mice formed unambiguously human BFU-E, CFU-GM and B cell colonies when stimulated with the appropriate growth factors. Accordingly, we have identified a relatively rapid and simple mechanism for isolating primitive human hematopoietic cells with stem cell-like properties. We anticipate that this strategy will be useful for experimental and therapeutic applications that require human stem cells in quantity.
 ...
PMID:CD34+, kit+, rhodamine123(low) phenotype identifies a marrow cell population highly enriched for human hematopoietic stem cells. 963 24

We describe our initial approach to clone and characterize genes expressed preferentially in thymic stromal cells, in an attempt to generate molecular reagents to study the role of these cells in thymopoiesis and thymic function. Thymic stromal cells were prepared from fetal thymic organ cultures by treating them with 2-deoxyguanosine and depleting the remaining hematopoietic cells with anti-CD45 antibody. A cDNA library was then prepared after subtraction and amplification by PCR. The cloned inserts were sequenced and compared for homology with known genes in the data base. Unidentified cDNAs were then examined for expression in normal and SCID thymus and in a set of SV40-transformed thymic epithelial cell lines, by Northern blotting and a dot blot assay. In this report we describe the development of the library and present a general description of the genes identified from the initial 249 cDNAs sequenced. Among these, a relatively high percentage (55%) do not show any homology to previously identified genes. Several genes with a limited expression pattern were selected for further study.
 ...
PMID:A subtractive PCR-based cDNA library made from fetal thymic stromal cells. 969 49

In vitro studies have provided little consensus on the kinetic abnormality underlying the myeloid expansion of chronic myelogenous leukemia (CML). Transplantation of human CML cells into non-obese diabetic mice with severe immunodeficiency disease (NOD/SCID mice) may therefore be a useful model. A CML cell line (BV173) and peripheral blood cells collected from CML patients in chronic phase (CP), accelerated phase (AP), or blastic phase (BP) were injected into preirradiated NOD/SCID mice. Animals were killed at serial intervals; cell suspensions and/or tissue sections from different organs were studied by immunohistochemistry and/or flow cytometry using antihuman CD45 monoclonal antibodies (MoAbs), and by fluorescence in situ hybridization (FISH) for the BCR-ABL fusion gene. One hour after injection, cells were sequestered in the lungs and liver, but 2 weeks later they were no longer detectable in either site. Similar short-term kinetics were observed using 51Cr-labeled cells. The first signs of engraftment for BV173, AP, and BP cells were detected in the bone marrow (BM) at 4 weeks. At 8 weeks the median percentages of human cells in murine marrow were 4% (range, 1 to 9) for CP, 11% (range, 5 to 36) for AP, 38.5% (range, 18 to 79) for BP, and 54% (range, 31 to 69) for BV173. CP cells progressively infiltrated BM (21%) and spleen (6%) by 18 to 20 weeks; no animals injected with the cell line or BP cells survived beyond 12 weeks. The rate of increase in human cell numbers was higher for BP (7.3%/week) as compared with CP (0.9%/week) and AP (0. 5%/week). FISH analysis with BCR and ABL probes showed that some of the human cells engrafting after injection of CP cells lacked a BCR-ABL gene and were presumably normal. We conclude that CML cells proliferate in NOD/SCID mice with kinetics that recapitulate the phase of the donor's disease, thus providing an in vivo model of CML biology.
 ...
PMID:The kinetics and extent of engraftment of chronic myelogenous leukemia cells in non-obese diabetic/severe combined immunodeficiency mice reflect the phase of the donor's disease: an in vivo model of chronic myelogenous leukemia biology. 969 28

The repopulating ability and homing potential of CD34+ cells isolated from either bone marrow (BM) or umbilical cord blood (UCB) was compared in NOD/SCID mice. Mice were sublethally irradiated (3.5 Gy) and within 24 h transplanted i.v. with 10(5)-10(6) CD34+ cells. Four weeks post-transplantation blood was collected from the tail vein for detection of human cells and after 6-7 weeks the mice were sacrificed and blood, BM, thymus, lymph nodes, spleen, liver, lung and kidney were harvested and single cells suspensions were made. Human cells were detected by flow cytometry, and staining was performed for CD34, CD45, and markers of the myeloid, and lymphoid lineages. CD34+ cells from UCB successfully engrafted into the NOD/SCID mice. Eighty-five percent of cells in BM of the mice were of human origin, depending on the dose of cells injected. In all other organs these percentages were always lower, and maximally 63, 13, 3 and 2% in spleen, liver, lung and kidney, respectively. Transplantation of CD34+ cells isolated from human BM, on the other hand, resulted in a very low percentage of human cells after 6-7 weeks of transplantation, not exceeding 3% of the cell suspension. Whether this difference in repopulating ability can be explained by an intrinsic qualitative difference or by differences in quantity of stem cells within the CD34+ compartment from UCB or BM remains to be determined.
 ...
PMID:Comparison of repopulating ability of hematopoietic progenitor cells isolated from human umbilical cord blood or bone marrow cells in NOD/SCID mice. 971 91

Stable gene transfer to human pluripotent hematopoietic stem cells (PHSCs) is an attractive strategy for the curative treatment of many genetic hematologic disorders. In clinical trials, the levels of gene transfer to this cell population have generally been low, reflecting deficiencies in both the vector systems and transduction conditions. In this study, we have used a pseudotyped murine retroviral vector to transduce human CD34(+) cells purified from bone marrow (BM) and umbilical cord blood (CB) under optimized conditions. After transduction, 71% to 97% of the hematopoietic cells were found to express a low-affinity nerve growth factor receptor (LNGFR) marker gene. Six weeks after transplantation into immunodeficient NOD/LtSz-scid/scid (NOD/SCID) mice, LNGFR expression was detected in 6% to 57% of CD45(+) cells in eight of nine engrafted animals. Moreover, proviral DNA was detected in 8.3% to 45% of secondary colonies derived from BM cells of engrafted NOD/SCID mice. Our data show consistent transduction of SCID-repopulating cells (SRCs) and suggest that the efficiency of gene transfer to human hematopoietic repopulating cells can be improved using existing retroviral vector systems and carefully optimized transduction conditions.
 ...
PMID:High efficiency gene transfer to human hematopoietic SCID-repopulating cells under serum-free conditions. 978 52


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