Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The study of structural/functional characteristics of the cell-surface glycoproteins of leukocytes has led to a better understanding of the differentiation and maturation of hematopoietic cells. We have assessed the ability of a unique metalloprotease that is secreted by the bovine fibrinous pneumonia pathogen Pasteurella haemolytica, to cleave cell-surface glycoproteins expressed on human leukocytes. Biochemical analysis shows that the O-glycosylated cell surface Ag CD34, CD43 (leukosialin), CD44 (hyaluronic acid receptor), and CD45 (leukocyte common Ag), are all cleaved by this protease. Although these enzyme-sensitive structures contain N-linked glycans, they are all extensively glycosylated with O-linked carbohydrates, which are especially abundant on CD34 and CD43. In contrast, the glycoproteins CD18/11a,b,c (leukocyte integrins), CD71 (transferrin receptor), HLA class I, and 8A3 Ag, which contain N-linked glycans but no O-sialo-glycans, were resistant to the action of the enzyme. Inasmuch as previous studies using glycophorin A had indicated that the substrate specificity of this enzyme may be uniquely restricted to the cleavage of O-sialoglycoproteins, we have designated this activity, P. haemolytica glycoprotease. Immunofluorescence analysis with a variety of antibodies to different epitopes of the P. haemolytica glycoprotease-sensitive structures indicate that this enzyme may have widespread applications in epitope-mapping studies, and represents a novel tool with which to study structure/function relationships for O-sialoglycosylated cell-surface proteins. However, most significantly these results suggest that the P. haemolytica glycoprotease may be of use in the affinity purification and recovery of clinically important leukocyte subsets, such as primitive hematopoietic progenitors that express CD34.
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PMID:Cleavage of the cell-surface O-sialoglycoproteins CD34, CD43, CD44, and CD45 by a novel glycoprotease from Pasteurella haemolytica. 137 28

The treatment effect of immunoselected allogeneic CD34+ blood cells was evaluated in two patients with poor graft function following BMT without evidence for immune-mediated rejection. Patient A had no signs of hematopoietic recovery up to day +34 post-BMT and patient B had normal leukocyte counts only with G-CSF support and remained platelet transfusion-dependent for > 200 days post-BMT. PBPC from the HLA-identical sibling BM donors were mobilized with G-CSF (2 x 5 micrograms/kg sc daily) for 5 days. Aphereses were performed on days 4 and 5 of G-CSF administration. CD34+ cells were separated from the pooled PBPC concentrates by immunoadsorption with the anti-CD34 moAb 12.8 in a biotin-avidin system. Patient A received 0.4 x 10(6) CD34+ and 4.3 x 10(5) CD3+ cells/kg body weight and patient B 3.4 x 10(6) CD34+ and 1.4 x 10(5) CD3+ cells/kg body weight. The trilineage repopulation of BM and the rapid improvement of peripheral blood parameters correlated with CD34+ cell infusion. Patients' blood and BM cell analyses proved the donor origin. Patient A died from CMV pneumonitis and multiorgan failure 27 days after CD34+ cell infusion (day +61 post-BMT). Patient B is still stable and in remission 260 days after CD34+ cell infusion (day +478 post-BMT). Neither patient suffered further exacerbation of GVHD). Thus, immunoselected allogeneic CD34+ blood cells might be appropriate for treatment of post-BMT graft failure.
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PMID:Treatment of poor marrow graft function with allogeneic CD34+ cells immunoselected from G-CSF-mobilized peripheral blood progenitor cells of the marrow donor. 753 62

A 67-year-old female was admitted with fatigue. Peripheral blood examination showed severe pancytopenia. Bone marrow biopsy revealed hypoplastic marrow. She was diagnosed as having aplastic anemia. Steroid pulse therapy was not effective. After treatment with erythropoietin (EPO) and granulocyte colony-stimulating factor (G-CSF), blasts which were positive for CD13, CD33, CD34 and HLA-DR and negative for myeloperoxidase appeared in the peripheral blood. At this time, bone marrow biopsy revealed myelofibrosis with increased blasts. Chromosome analysis showed 46XX, add (1) (p36), add (1) (q44), -2, -5, del (7) (q11), -12, +3mar. She died of pneumonia despite chemotherapy with etoposide. Administration of EPO and G-CSF may have led to the rapid development of leukemia and myelofibrosis.
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PMID:[Transformation of aplastic anemia to acute myeloid leukemia with myelofibrosis following treatment with granulocyte colony-stimulating factor and erythropoietin]. 877 84

A 63-year-old male was admitted because of pneumonia. Peripheral blood findings showed pancytopenia with increase of blasts. A bone marrow specimen showed hypocellular marrow with increase of blasts. The blasts were positive for CD7, CD34, and HLA-DR and negative for other lymphoid antigens and myeloid antigens involving myeloperoxidase. Rearrangement of immunoglobulin heavy chain was demonstrated by Southern blotting analysis. T cell receptor beta, T cell receptor gamma and immunoglobulin light chain rearrangement were negative. A diagnosis of stem cell leukemia was made. In vitro, the blasts did not respond to recombinant human granulocyte colony-stimulating factor (rhG-CSF), cytarabine (Ara-C) and all-trans retinoic acid (ATRA). However, in the blasts of culture without cytokeins, CD33 expression was newly induced. Remission was not obtained by chemotherapies with cyclophosphamide, etoposide, prednisolone and Ara-C. Four months later, marrow specimens showed hypoplasty with myelofibrosis. One year later, the blasts showed CD33 expression with negative myeloperoxidase. The leukemia was transformed to minimally differentiated myeloid leukemia from stem cell leukemia. This condition was thought to be "smoldering leukemia" because of the slow development and refractoriness to chemotherapy. Nineteen months later the patient died due to respiratory failure by pneumonia and pulmonary bleeding despite therapy.
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PMID:[Smoldering leukemia with CD7.CD34(+), immunoglobulin heavy chain rearrangement (+) and hypoplastic marrow with myelofibrosis]. 902 57

A patient with non-Hodgkin's lymphoma who received a CD34-selected autologous peripheral blood stem cell transplant (PBSCT) developed cytomegalovirus retinitis, adenovirus-associated haemorrhagic cystitis (HC) and fatal herpes simplex virus pneumonia. Depletion of mature T cells from the graft and a persistent decrease in CD4+ lymphocytes following PBSCT may have predisposed this patient to such viral infections. Infusion of cryopreserved autologous PBSC (containing mature T cells) was effective for adenovirus-associated HC. Immunosuppression and resultant viral infections may affect patients receiving CD34-selected autologous transplantation.
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PMID:Early viral complications following CD34-selected autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma. 963 8

We report 2 cases of agranular CD2- CD4+ CD56+ non-Hodgkin lymphoma in which skin seemed to be the primary site. A 21-year-old woman's initial symptom was a skin nodule on the right cheek. She also had tumors in the nasopharynx, and the bone marrow subsequently became involved. No lymphadenopathy was present. She experienced complete remission after dose-intensified therapy with cyclophosphamide, hydroxydaunomycin, vincristine [Oncovin], and prednisone (CHOP), but the disease relapsed in the central nervous system 6 months later. An 81-year-old man experienced an 11-month history of skin nodules in the left forearm. On admission, he had a bone marrow infiltration of lymphoma cells. He died of pneumonia during chemotherapy. The malignant cells of the 2 patients had similar morphologic features, with a monocytoid nucleus and no cytoplasmic granules. The cells in both cases showed a unique phenotype: CD2-, CD3-, CD4+, CD8-, CD13-, CD14-, CD34-, CD16-, CD56+, CD57-, HLA-DR-positive. Staining for peroxidase and alpha-naphthyl butyrate esterase was negative. The T-cell receptor beta, gamma, delta, IgH, kappa, lambda genes were of germ line configurations. The DNA of Epstein-Barr virus was not detected from the bone marrow cells by polymerase chain reaction. Only 3 other cases with similar phenotypes have been reported; all had skin lesions. Although the origin of these cells remains unknown, we propose that this is a distinct clinicopathologic entity.
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PMID:A cutaneous agranular CD2- CD4+ CD56+ "lymphoma": report of two cases and review of the literature. 1043 11

Allogeneic bone marrow transplantation is limited by the availability of suitable HLA-matched donors and the risk of graft versus host disease (GvHD). In an attempt to overcome these limitations umbilical cord blood (UCB), has become a further alternative. UCB transplantations in Austria were started in 1991. As of September 31, 1998, six patients have been transplanted. Diagnoses were severe aplastic anaemia (SAA) (n = 2), acute lymphoblastic leukaemia (ALL) (n = 1), familial hemophagocytic syndrome (FHL) (n = 2) and chronic myelomonocytic leukaemia (CMML) (n = 1). Three patients received UCB grafts from HLA-identical siblings and three patients from unrelated donors, of whom two were disparate at two HLA loci (A/B) and one mismatched at one locus (C). Five patients were engrafted with complete donor hematopoiesis, with a median time of 26.5 days (range 14 to 39 days) to an ANC count of > or = 0.5 x 10(9)/L and a median time of 42.5 days (range 24 to 67 days) to a platelet count of > or = 20 x 10(9)/L. One patient with FHL had partial engraftment and died due to reactivation of cytomegalovirus (CMV) infection and CMV pneumonia on day +25. Of the five patients surviving the post-transplant period, one with CMML had a relapse on day +128 and died after a HLA-matched bone marrow transplantation from the same sibling donor in the second relapse. Another patient with ALL relapsed on day +200 but is still alive under palliative treatment; one patient with SAA showed graft rejection and autologous hematopoietic reconstitution and later had a successful CD34(+)-selected allogeneic peripheral stem cell transplant from a C-locus mismatched unrelated donor. Two patients (one with SAA and one with FHL) are alive with complete remission of the underlying disease. This report reflects the experience and results of UCB transplantation in Austria and discusses the position of UCB transplantation in the context of the other stem cell alternatives available today.
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PMID:Transplantation of related and unrelated umbilical cord blood stem cells in Austria. Austrian Working Party for Stem Cell Transplantation. Austrian Society of Hematology and Oncology. 1040 93

In the absence of a donor alternative a stem cell transplantation consisting of two cord blood components originating from the haploidentical brother was performed in a 2-year-old girl with c-ALL, early CNS relapse and 7% of blast cells in the BM 14 days before transplantation. Because of various ongoing infectious complications at that time, 1/8 of the immunogenetically acceptable sibling cord blood was ex vivo expanded 10 days before the transplantation date. The total CB consisting of 1.17 x 10(9) NC was cryopreserved in four separate bags. The one containing 1/8 of the total CB with 1.4 x 10(8) NC CliniMACS selected CD34+ cells was expanded in the presence of 100 ng/ml G-CSF, 100 ng/ml TPO and 100 ng/ml flt3-L in 10% autologous CB plasma and X-VIVO 10 medium at day -10 before transplantation. This expanded cell population was sterile and consisted of about 60% granulocytic cells (CD13+, CD15+), about 30% myelomonocytic cells (CD14, HLA-DR+), 5.2% megakaryocytes (CD61+) and 1.2% CD34+ cells. The proportion of T (CD3+), NK cells (CD56+) as well as dendritic cells (CD83+) was below 0.2%. The unseparated CB infused at day 0 and +1 consisted of a total of thawed 4.4 x 10(7) NC/kg BW, 5.8 x 10(4) CFU-GM/kg BW, 1.54 x 10(5) CD34+cells/kg BW and 7. 73 x 10(2) LTC-IC/kg BW. In addition, the 1 x 10(7) NC/kg BW ex vivo expanded cells representing 1.9 x 10(4) CFU-GM/kg BW, 1.13 x 10(5) CD34 cells/kg BW and 4.37 x 10(2) LTC-IC/kg BW, were infused at day +1. At day +2 after transplantation the patient revealed a focal pneumonia on X-ray with generalized sepsis and became catecholamine dependent. From day +4 the patient received 280 microg/m2 G-CSF. At day +5 she developed an erythroderma, which could not be identified as acute GVHD by biopsy. Early engraftment with leukocyte counts at days 8 and 14 were 350 and 700/microl, ANC 310 and 410/microl, respectively. Donor cells determined by chimerism analysis were 97% and 98% in the periphery at this early time. Most importantly, the pneumonia as well as the septicemia subsided within a few days. Notably, as well is the clearly shortened aplastic phase observed after this simultaneous CB cell component transplantation. The patients T cell and NK cell reconstitution could be detected at day +37 with 330 CD3+ cells/microl and 40 CD56+ cells/microl, respectively. The time to reach an absolute platelet count of 20 000 (50 000)/microl was 75 (103) days. The disease-free survival now exceeds 1 year in complete remission without chronic GVHD or any other health problems. These data show that the applicability of ex vivo expanded committed progenitors and LTC-IC, even in high risk leukemia at the time of transplantation, is feasible and can provide sufficient myeloid progenitors resulting in rapid engraftment able to clear bacterial pneumonia and sepsis. In addition, accelerated hematopoietic reconstitution apparently served as a well functioning platform for definitive graft-versus-leukemia activity. This transplantation of defined ex vivo generated components presents a feasible and generally applicable approach and may open a promising new avenue for cell therapy in malignant diseases.
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PMID:Simultaneous cord blood transplantation of ex vivo expanded together with non-expanded cells for high risk leukemia. 1046 29

We report on a 19-month-old boy with refractory T-cell acute lymphoblastic leukemia who underwent allogeneic peripheral blood stem cell transplantation using positively selected CD34 cells from his HLA two-loci mismatched mother. The conditioning regimen consisted of busulfan (140 mg/m2/d for 2 days), total body irradiation (12 Gy) and melphalan (210 mg/m2). The patient received cyclosporin A for graft-versus-host disease (GVHD) prophylaxis. The CD34-positive cells were separated using an immunomagnetic cell-separation system (Isolex 50). The number of infused CD34-positive cells was 4.4 x 10(6)/kg. Successful engraftment was confirmed on day 14 by fluorescent in situ hybridization of X chromosomes. The patient experienced severe diarrhea due to thrombotic microangiopathy (TMA) following acute GVHD, and died on day 71 of human herpes virus type 6 pneumonitis. Stem cell transplantation using CD34 positively selected cells from HLA-mismatched related donors may be a useful treatment with low incidence of severe GVHD, but many problems remain to be overcome, including severe viral infections and TMA.
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PMID:[Infantile T cell acute lymphoblastic leukemia complicated by thrombotic microangiopathy and human herpes virus 6 infection after allogeneic peripheral blood stem cell transplantation using CD34-positive cells]. 1048 41

Multiple sclerosis (MS) is an immune-mediated disease that may be amenable to high-dose immunosuppression with peripheral blood stem cell transplantation (SCT) in selected patients. Five MS patients (all women, ages 39-47 years) received granulocyte colony-stimulating factor (G-CSF) for stem cell mobilization, CD34 cell selection for T-cell depletion, a preparatory regimen of busulfan (1 mg/kg x 16 doses) and cyclophosphamide (120 mg/kg), and antithymocyte globulin (10 mg/kg x 3 doses) at the time of stem cell infusion. Days required to recover absolute neutrophil count >500 were 12 to 14 and platelet count >20,000 were 17 to 58. Posttransplantation infectious complications in the first year after SCT occurred in 3 of 5 patients, and 1 patient died at day 22 after SCT from influenza A pneumonia. Neuropathologic study in this patient showed demyelinating plaques with surrounding macrophages but only rare T cells. In 2 patients, MS flared transiently with G-CSF. Magnetic resonance imaging gadolinium enhancement was present in 3 of 5 patients before transplantation and 0 of 4 after SCT. There were cerebrospinal fluid oligoclonal bands at 1 year after SCT, similar to the pretransplantation assays. Sustained suppression of peripheral blood mononuclear cell proliferative responses to myelin antigens occurred after SCT, but new responses to some myelin peptide fragments also developed after SCT. In 1 patient, enzyme-linked immunospot (ELISPOT) assays done 9 months after SCT showed a predominant T helper 2 (Th2) cytokine pattern. Neurological progression of 1 point on the extended disability status scale was seen in 1 patient 17 months after SCT. Another patient who was neurologically stable died abruptly 19 months after SCT from overwhelming S. pneumoniae sepsis. The remaining patients have had stable MS (follow-up, 18 and 30 months). In summary, our experience confirms the high-risk nature of this approach. Further studies and longer follow-up would be needed to determine the significance of new lymphocyte proliferative responses after SCT and the overall effect of this treatment on the natural history of MS.
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PMID:Peripheral blood stem cell transplantation in multiple sclerosis with busulfan and cyclophosphamide conditioning: report of toxicity and immunological monitoring. 1107 Dec 62


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