Prognostic relevance of surface markers in adult de novo acute myeloblastic leukemias: a prospective study of the Groupe d'Etude Immunologique des Leucémies (G.E.I.L.).
Explore the source record for details and available documents.
Adolescent↗
Biomedical subjects
L Campos
Publications and source records attributed to L Campos.
[Evolution of the concept of heath center in the context of the new National Health Service Act and the development of health administration at the local level].
The authors consider the recently passed about the Portuguese health system reform, namely bills Laws 48/90 and 10/93 (the Bases for Health Law and the National Health Service Act) and they existing some contradictions between the two Laws. In this paper the authors try to adopt point out legislation, mainly the Bases for Health Law from August 24, 1990, as a standard for the conceptualization of a model. One of the proposals in this law, the Health Area, is examined according to the functional contents expressed therein. The authors then probe the concept further, suggesting a local health administration function, at in a Health Area and aimed based a population of about 30,000 inhabitants (from 10 to 50 thousand) and headed by a local Health Administration. The duties and the functional and organizational structure of this body are defined; suggestions for its composition are also advanced. Considering the organizational structure, the authors suggest some services to be supervised by the Local Health Administration: a Public Health Service, a Secretariat and Accounting Service, a Social Service and other. The new concept of Health Center, as the primary care providing unit, is introduced, as is the idea of a Family Medicine Unit, whose functions, definition and scope are proposed.
Catchment Area, Health↗
Genetically engineered grafts to study xenoimmunity: a role for indirect antigen presentation in the destruction of major histocompatibility complex antigen deficient xenografts.
BACKGROUND: The genetic engineering of xenogeneic donor species for transplantation may provide a means of attenuating the potent immune response elicited by tissues from foreign species. Because of their well-established role in allograft rejection, a logical target for genetic manipulation is the genes encoded by the major histocompatibility complex (MHC). In the current study we examined whether skin, heart, or pancreatic islet xenografts harvested from lines of transgenic mice rendered deficient in MHC antigen expression by gene disruption would exhibit a survival benefit when transplanted to xenogeneic rat recipients. In addition, we characterized the in vitro response of rat T cells to normal and MHC-deficient mouse cells. METHODS: Skin, heart, and pancreatic islet grafts were harvested from control C57Bl/6 and each of three lines of mice deficient in MHC antigen expression. MHC-deficient lines included (1) mice selectively lacking MHC class I antigens (CID), produced by disruption of the beta-2 microglobulin gene; (2) mice lacking MHC class II expression (CIID), produced by targeting the I-A beta-chain gene; and (3) mice devoid of both class I and class II molecules (CI,IID). RESULTS: In contrast to the prolonged survival that has been observed for certain allografts deficient in MHC antigen expression, we did not detect significant extension of survival in the case of xenografts. Using in vitro assays of T-cell function, we demonstrated that rats that rejected grafts lacking MHC expression evidenced sensitization of T cells specific for graft antigens presented by rat antigen-presenting cells. CONCLUSIONS: The strategies of gene targeting of donor species to produce less immunogenic xenografts may be hampered by the presence of a strong response through the indirect pathway of immunity. Immune intervention directed at the indirect antigen presentation pathway may be of benefit in xenotransplantation.
Animals↗
Intrathymic transplantation promotes survival of islet xenografts (rat-->mouse).
Explore the source record for details and available documents.
Animals↗
High expression of bcl-2 protein in acute myeloid leukemia cells is associated with poor response to chemotherapy.
The BCL-2 proto-oncogene encodes a mitochondrial protein that blocks programmed cell death. High amounts of bcl-2 protein are found not only in lymphoid malignancies, but also in normal tissues characterized by apoptotic cell death, including bone marrow. Using a monoclonal antibody to bcl-2 protein, we analyzed 82 samples of newly diagnosed acute myeloid leukemia. The number of bcl-2+ cells in each sample was heterogeneous (range, 0% to 95%), with a mean of 23%. The percentage of bcl-2+ cells was higher in M4 and M5 types, according to French-American-British classification, and in cases with high white blood cell counts. bcl-2 expression was also correlated with that of the stem cell marker CD34. In vitro survival of leukemic cells maintained in liquid culture in the absence of growth factors was significantly longer in cases with a high percentage of bcl-2+ cells. High expression of bcl-2 was associated with a low complete remission rate after intensive chemotherapy (29% in cases with 20% or more positive cells v 85% in cases with less than 20% positive cells, P < 10(-5)) and with a significantly shorter survival. In multivariate analysis, the percentage of bcl-2+ cells (or the blast survival in culture), age, and the percentage of CD34+ cells were independently associated with poor survival.
Acute Disease↗
Potential role for non-HLA-restricted cytotoxic cells in the immune surveillance of acute leukemia.
The observation of more frequent leukemias in immune deficiencies of the non-HLA-restricted cytotoxic cell system and the participation of this system in the anti-leukemic effect of allogeneic bone marrow transplantation in acute leukemia indicate that these cells might play a role in the immune surveillance against leukemia. In order to find more direct evidence of this role we studied the susceptibility of leukemic cells to lysis by non-HLA-restricted cytotoxic cells, the functional value of these cells in leukemic patients in complete remission (CR), and expression by leukemic cells of adhesion molecules CD54 and CD58, which play a role in the adherence between cytotoxic cells and their targets. Our results are concordant to confirm a potential role of non-HLA-restricted cytotoxic cells in the immune surveillance of acute leukemia based on increased relapse rate in acute myeloid leukemia patients with no inducible lymphokine-activated killer (LAK) cell activity during CR, short survival of acute lymphoblastic leukemia patients whose blast cells are resistant to lysis by LAK cells, and poor overall prognosis of leukemias which do not express CD58.
Antibodies, Monoclonal↗
Examination of the mechanisms responsible for tolerance induction after intrathymic inoculation of allogeneic bone marrow.
OBJECTIVE: This study examined the immunologic mechanism(s) responsible for the induction of transplantation tolerance in rats pretreated with intrathymic inoculation of donor strain bone marrow. SUMMARY BACKGROUND DATA: Induction of unresponsiveness may involve deletion and/or inactivation of donor-reactive T-cell precursors maturing in a thymus harboring donor alloantigen or generation of regulatory/suppressor cells. It was reasoned that, if unresponsiveness is caused by deletion of alloreactive clones, the presence of additional thymic tissue devoid of donor alloantigen permits normal maturation of T-cells and, thus, prevents induction of tolerance. However, if unresponsiveness were primarily mediated by regulatory/suppressor cells, the presence of noninoculated thymic tissue should not affect the induction of tolerance. METHODS: Three strategies were used to define the cellular basis of cardiac and islet allograft survival in WF recipients of intrathymic LEW donor bone marrow as follows: (1) inoculation of bone marrow either into the native thymus and/or into an ectopic thymus, (2) limiting dilution analyses of the frequency of precursor cytotoxic T-lymphocytes (CTLp), and (3) adoptive transfer to syngeneic secondary hosts. RESULTS: Inoculation of bone marrow into only one lobe of the native thymus and/or into an ectopic thymus did not promote consistent survival of subsequent LEW cardiac allografts. Tolerant hosts displayed significant reductions in CTLp frequencies against donor alloantigens. Adoptive transfer of spleen cells from tolerant WF hosts harboring long-standing cardiac allografts led to permanent survival of LEW cardiac allografts in all secondary recipients. However, transfer of spleen cells from WF animals that received intrathymic LEW bone marrow (but no cardiac allograft) did not promote survival of LEW cardiac allografts in naive secondary hosts. CONCLUSIONS: These results indicate that the unresponsive state after intrathymic inoculation of bone marrow cells is primarily mediated by deletion and/or inactivation of donor-specific T-cell precursors maturing in a chimeric thymus. The demonstration by adoptive transfer studies of putative regulatory/suppressor cells suggested an important role for the persistence of donor alloantigen (supplied by a vascularized allograft) in the maintenance of the unresponsive state.
Animals↗
Prolonged survival of rat orthotopic liver allografts after intrathymic inoculation of donor-strain cells.
Permanent donor-specific tolerance to tissue or organ allografts can be readily achieved without immunosuppression by administration of donor lymphohematopoietic cells to neonatal rodents. In adult recipients, however, induction of transplantation tolerance by this strategy generally requires intensive cytoablative conditioning of the recipient. We have now demonstrated that intrathymic inoculation of donor bone marrow or hepatic cells in conjunction with a single dose of antilymphocyte serum is effective in prolonging survival of DA rat orthotopic liver allografts in LEW strain recipients, which ordinarily rapidly reject such transplants. The unresponsive state achieved is donor-specific, as evidenced by the failure of intrathymic inocula of third-party WF cells to promote survival of LEW recipients of orthotopic DA liver allografts. Moreover, intravenous administration of the donor cells fails to extend liver allograft survival, demonstrating that the inoculum must be present in the thymus to promote unresponsiveness. Established DA liver allografts induced a state of systemic tolerance in LEW hosts, allowing their subsequent acceptance of donor-strain skin allografts. We hypothesize that the unresponsive state achieved by intrathymic inoculation of donor cells may result from the deletion or functional inactivation of alloreactive clones in a thymus bearing donor alloantigens. In this regard, cells of the macrophage/dendritic lineage (descendants of the bone marrow inoculum or hepatic Kupffer cells) may play a critical role by promoting thymic microchimerism and exerting modulatory effect on T cell development.
Animals↗
S100 protein and neuron-specific enolase on monocytic leukemic CD1+ cells, probable precursors of Langerhans cells.
Langerhans cells are characterized by specific markers, such as Birbeck granules and CD1a antigen. S100 protein and neuron-specific enolase are less specific but are expressed only on Langerhans cells among the cells of the phagocytic mononuclear system. In this study, the expression of these two antigens on many monocytic leukemic cells is shown. These cells could be precursors of Langerhans cells which have been transformed into malignant cells.
Antigens, CD↗
Peripheral blood stem cells harvested after chemotherapy and GM-CSF for treatment intensification in patients with advanced lymphoproliferative diseases.
Peripheral blood stem cells (PBSC) from 15 patients with advanced non-Hodgkin's lymphoma (NHL), two patients with chronic lymphocytic leukemia, and two patients with myeloma were collected by continuous-flow leukapheresis after chemotherapy with MIV (mitoxantrone, ifosfamide, and etoposide, five patients) or high-dose cyclophosphamide (14 patients), followed by administration of GM-CSF. Sixteen patients (84%) had persistent marrow involvement at time of inclusion. Results were compared to those obtained in a control group of similar age and disease status in whom collection had been performed after MIV chemotherapy alone. The number of mononuclear cells, granulocyte-macrophage colony-forming units (CFU-GM), CD34+ cells were higher in GM-CSF treated patients with a lower mean number of leukapheresis (3.5 versus 6.4). Among the 19 patients harvested after chemotherapy plus GM-CSF, more progenitor cells were obtained in the cyclophosphamide group than in the MIV group. In all these patients except one, the number of mononuclear cells was sufficient to realize a transplantation. Seventeen patients received intensification with BEAM regimen (8 patients) or cyclophosphamide plus etoposide and total body irradiation (9 patients). Two patients failed to reconstitute correct hematopoiesis and three early toxic deaths occurred for a total of five procedure-related deaths. Nine of these 17 patients are in persistent complete remission with a median post-transplant follow-up of 18 months. Time to reach granulocyte and platelet recovery was not correlated with the number of mononuclear cells, CFU-GM, granulocyte-erythroid-macrophage-megakaryocyte colony-forming units (CFU-GEMM), CD34+ cells, and CD34+ CD33- cells but with the number of previous chemotherapy regimens. PBSC harvesting is achievable after chemotherapy plus GM-CSF in heavily pretreated patients with persistent marrow involvement. Moreover, these cells are able to reconstitute correct hematopoiesis after intensive treatment in these patients.
Adult↗
Laparoscopic hernia repair: use of a fenestrated PTFE graft with endo-clips.
A prospective study of 15 patients undergoing elective laparoscopic herniorrhaphy was performed using the introduction of a polytetrafluorethylene (PTFE, GORE-TEX) patch fenestrated around the edges to facilitate the use of an Endo-Clip applier. Patient tolerance was increased, and time lost from work was reduced. Two patients treated for prostatitis resumed sexual activity within the first 10 days with no recurrences or intra-abdominal infections. Fenestration of the PTFE patch was possible without fraying the material and without compromising the strength of the patch. The Endo-Clip applier secures the patch to the ligamentous structures. Initial cases were followed for 6 months.
Adult↗
Intrathymic inoculation of donor cells promotes survival of rat orthotopic liver allografts.
Explore the source record for details and available documents.
Animals↗
[Naproxen sodium in the treatment of otitis].
OBJECTIVE: To assess the analgesic and anti-inflammatory value of sodium Naproxen in the treatment of otitis. DESIGN: A prospective study. There were interventions, but no controls. There was not a random distribution of the sample. SITE. Outpatient clinics in a Santander hospital. PATIENTS AND OTHER PARTICIPANTS: Patients presenting symptoms of acute or chronic otitis. INTERVENTIONS: A group of 20 patients with acute otitis and a second group of 15 with chronic otitis were treated normally; while 20 other patients suffering acute otitis and 17 with chronic otitis received in addition to normal treatment 550 mg of sodium naproxen every 12 hours. MAIN MEASUREMENTS AND RESULTS: The evolution of the clinical description was evaluated along the following parameters: perforation of the tympanum, otorrhea, pain, vertigo, migraines, hypoacusis and audiometries in acute cases of otitis; and all these and also tympanic biopsy in chronic cases. The results obtained indicated a statistically significant anatomical-pathological improvement in chronic cases of otitis treated with sodium naproxen; whereas in cases of acute otitis, these differences were observed in parameters such as hypoacusis, tympanometry, perforation of the tympanum and effectiveness of and tolerance towards additional treatment with sodium Naproxen. CONCLUSIONS: On the basis of the study's results as well as the high level of tolerance and absence of undesirable effects, we made a positive evaluation of the introduction of the aforesaid anti-inflammatory into the normal treatment of cases of otitis.
Adolescent↗
Clinical significance of multidrug resistance P-glycoprotein expression on acute nonlymphoblastic leukemia cells at diagnosis.
To evaluate the clinical value of the expression of multidrug resistance P-glycoprotein (P-170) on the surface of acute nonlymphoblastic leukemia (ANLL) cells, we analyzed specimens from 150 newly diagnosed patients for staining with MRK16, a monoclonal antibody (MoAb) that binds to an external epitope of P-170. Other surface markers (CD13, CD14, CD15, and CD34) were studied by the same technique. A marker was considered positive when 20% or more cells were stained. Of 150 samples, 71 were P-170-positive. These cases did not differ from P-170-negative cases with regard to age, sex, initial white blood cell (WBC) counts, or French-American-British (FAB) type (except for M3 ANLL, which were more frequently negative). However, leukemias arising from previous myelodysplastic syndrome (MDS) and therapy-induced leukemias were more frequently P-170-positive. CD34 and P-170 expression were significantly associated. All patients were treated by intensive chemotherapy. Complete remission (CR) rates were significantly lower in P-170-positive (23/71, 32%) than in P-170-negative cases (64/79, 81%) (P less than 10(-5)). CD34 positivity was also associated with a low remission rate (P less than 10(-5)). Survival was shorter for P-170- and CD34-positive patients (P less than 10(-5)). The prognostic value of both markers was confirmed in multivariate analysis. CR duration was also shorter for P-170-positive cases, but the difference is less significant (P = .05). It is concluded that P-170 analysis may be an important tool for predicting the outcome of intensive chemotherapy in ANLL patients.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Association of t(15;17) and t(8;21) in the initial phase of an acute promyelocytic leukemia.
Two clones were observed at the initial phase of an acute myelogenous leukemia (AML): 46,XX,t(15;17) and 46,XX,t(8;21),t(15;17). Clinical, immunologic, and morphologic findings were in favor of expression of both chromosomal anomalies. Relapse occurred after 12 months of complete remission with typical acute promyelocytic leukemia (APL) syndrome when t(15;17) alone was then most predominant.
Antigens, CD↗
Specific binding of anti-N-acetyllactosamine monoclonal antibody 1B2 to acute myeloid leukaemia cells.
1B2 is an IgM monoclonal antibody binding to glycoconjugates bearing the terminal N-acetyllactosamine structure. It agglutinates human erythrocytes. Various cell lines, peripheral blood leucocytes, normal marrow and blast cells from 179 acute myeloid leukaemia (AML) and 11 acute lymphoblastic leukaemia (ALL) patients were tested for reactivity with 1B2. Myelomonocytic (CFU-GM), erythroid (BFU-E), mixed (CFU-GEMM) and leukaemic (CFU-L) progenitor cells were tested in clonogenic assays. Granulocytes, monocytes, myeloid cell lines and 152 out of 179 AML were positive. All FAB subtypes were equally recognised. Lymphocytes, T-cell and Burkitt's cell lines, and 10 of 11 ALL samples were negative. 1B2 inhibited partially day 7 CFU-GM, whereas it was not toxic for BFU-E, CFU-GEMM and day 14 CFU-GM. Leukaemic clonogenic cells were killed in 33 out of 36 AML (more than 40% growth inhibition). 1B2 identifies the more mature steps of myeloid differentiation. It may be useful in the diagnosis of AML, and is a candidate for remission marrow purging before autologous transplantation.
Amino Sugars↗
Prolongation of rat pancreatic islet allograft survival by anti-CD2 monoclonal antibody treatment.
Explore the source record for details and available documents.
Animals↗
Surface marker expression in acute myeloid leukaemia at first relapse.
Surface markers were studied at first relapse in 66 cases of acute myeloid leukaemia (AML), using a panel of five monoclonal antibodies directed to CD13, CD14, CD15, CD33 and CD34 antigens. At time of relapse, there was increased expression of CD33 (P = 0.002) and CD34 (P = 0.0001), and decreased expression of CD13 (P = 0.004) and CD15 (P = 0.0001) antigens by comparison to initial diagnosis. There was no strict correlation with the FAB classification. However, CD13 and CD33 expression changes preferentially affected granulocytic leukaemias. At relapse, CD14 and CD34 were significantly more expressed in monocytic than in granulocytic AML (P = 0.01 and 0.003 respectively). In a multivariate analysis, CD34 expression was associated with a low CR rate (P = 0.001) and short survival (P = 0.05), whereas CD15 expression was associated with long survival (P = 0.0004). These results suggest that AML tends to relapse with a less differentiated phenotype than observed at diagnosis and that AML with less differentiated phenotype is of poor prognosis after first relapse, as also observed at diagnosis.
Acute Disease↗