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Biomedical subjects

C Cordonnier

Publications and source records attributed to C Cordonnier.

At least 181 records · Page 10Linked to original sources
PubMed1987

Reconstitution of cytotoxic T lymphocyte activity following allogeneic bone marrow transplantation in man.

Longitudinal studies over an eight-month period have been performed to follow the T killer response restoration after allogeneic bone marrow transplantation (BMT). The capacity of the patient's peripheral blood mononuclear cells (PBM) to develop cytotoxic effector cells directed either against allogeneic cells or against Epstein-Barr virus (EBV) or Herpes-simplex virus-1 (HSV-1)-infected syngeneic cells was tested monthly. The data suggest that in most cases the cytotoxic T lymphocyte (CTL) activity, either allospecific or directed against EBV and the HSV-1 specific killer (HNK) responses, is quickly reconstituted in BMT patients. Roughly, these activities seem to be normal after two months following classic nondepleted grafting. However, in the two patients who had received a T-cell-depleted graft, the restoration was delayed. Furthermore, in the majority of the patients, once reconstituted the killer responses were relatively stable and the occurrence or absence of graft-versus-host diseases (GVHD) did not significantly modify these responses.

Adolescent↗
PubMed1987

High levels of anti-cytoskeleton autoantibodies are frequently associated with chronic GVHD.

Twenty-two patients (acute myeloid leukaemia 13, acute lymphoid leukaemia 5, chronic myeloid leukaemia 4) with an average age of 25 years (range 8-36 years), had received allogeneic bone marrow transplantation (BMT) from an HLA identical sibling. The BMT recipients were followed up for a period of 4-65 months. All patients were given cyclophosphamide, total body irradiation and methotrexate in order to prevent graft-versus-host disease (GvHD). Eleven of 22 patients exhibited chronic graft versus host disease (cGvHD) (extensive in five, limited in six at the time of the study) assessed by clinical and histological parameters. Serum samples were collected from these patients, before BMT (except in one case) and then every 2 or 3 months. Sequential studies to determine the presence of autoantibodies against cytoskeletal proteins (actin, tubulin, myosin), dsDNA and dDNA in these sera were performed by an ELISA method. Simultaneously, immunoelectrophoresis and measurement of complement fractions C3, C4 were performed on each sample. High levels of autoantibodies against cytoskeletal proteins were found in 10/11 patients with cGvHD and were absent in 11/11 patients without cGvHD; none of them exhibited anti-DNA activity. At the same time, C4 levels were decreased in seven of these patients with cGvHD. Monoclonal immunoglobulins IgG and IgM (2-15 g/l) were found in 8/11, but the antibody activity was never found to be located within the M component. These results show a direct relationship between the presence of these autoantibodies and occurrence of cGvHD and indicate that they may constitute an immunological marker related to this complication. However, their predictive value is not clearly evident in this retrospective series as in some patients they preceded clinical signs of cGvHD, whereas in others they were associated with the onset of cGvHD.

Adolescent↗
PubMed1987

In vitro inhibition of hematopoiesis by HNK1, DR-positive T cells and monocytes after allogeneic bone marrow transplantation.

Blood CFU-GM and BFU-E, grown from 17 patients who had undergone allogeneic bone marrow transplantation (BMT), were studied by the plasma-clot technique before day 45, and at a time when their blood count was approximately normal. The number of colonies varied from one patient to another, but was always lower than in normal subjects. Removal of cells forming rosettes with sheep erythrocytes (E+C) increased colony growth in four out of eight cases, whereas removal of adherent cells (AC) had the same effect in five out of six cases. Addition of E+C or AC after their initial removal restored the inhibition of colony growth. This suppression was noted at a 1:1 to 8:1 cellular ratio and ranged from 25% to 75%. The phenotype of the suppressive cells was further characterized by complement-mediated lysis with monoclonal antibodies (MoAbs) and fluorescent labeling. Two types of cells associated with inhibition of colony growth were identified: the first were E+C positive, characterized by the T3, HNK1, DR, and T8 determinants; the second were identified by the MO2 MoAb, indicating their monocytic origin, together with their properties of adherence. Similar suppressor cells of CFU-GM were found in the marrow of two other allogeneic BMT patients. A direct suppressive effect of the two types of cells was demonstrated in one experiment when MO2+ and/or HNK1+ cells collected by cell sorting were added back to cultures depleted in MO2+ and HNK1+ cells by complement-mediated lysis and were both found to decrease colony growth. Purified HNK1+ cells led to moderate inhibition of colony growth, which was not enhanced by increasing their concentration. This suppressive effect of hematopoiesis could be the consequence of an allogeneic reaction, since no inhibition was affected by T cells or monocytes in seven autologous BMTs and one syngeneic BMT.

Adolescent↗
PubMed1987

Long lasting IgG subclass and antibacterial polysaccharide antibody deficiency after allogeneic bone marrow transplantation.

Serum IgG subclasses were measured by a competitive indirect immunoassay with monoclonal antibodies in 31 leukemic patients before and after bone marrow transplantation. Antibodies to Hemophilus influenzae type b (Hib) capsular polysaccharide were determined in 28 cases. Abnormally low or borderline subclass (mostly IgG2 and IgG4) levels were found late after transplant in 23 infected and noninfected patients. These levels persisted for as long as 25 months, in association with low or borderline IgA levels in 78% of the cases. IgG2, IgG4, and IgA often showed a parallel evolution, whereas IgG1, IgG3, and IgM often varied together in the opposite way. Class but not subclass deficiencies were more frequent in patients with graft-v-host disease (GVHD). Subclass abnormalities predominated in infected patients, with mean levels correlating with the severity of infections; however, the abnormalities are not clearly predictive of infections in individual cases. Most patients with Hib pneumonia showed virtually no IgG antibody response to Hib, and one-half of the patients had a moderate IgM and IgA response. In the whole series, many sera collected greater than 1 year after graft contained very low or undetectable antibodies. Correlation between anti-Hib antibody and IgG2 levels was significant but weak because of discrepancies that were only partially explained by the subclass distribution of the antibodies.

Antibodies, Bacterial↗
PubMed1987

Mixed blood chimerism in T cell-depleted bone marrow transplant recipients: evaluation using DNA polymorphisms.

We have used DNA sequence polymorphism analysis to document engraftment after T cell-depleted bone marrow transplantation (BMT), with a selected panel of four DNA probes. In contrast to nondepleted BMT recipients, the patients who received T cell-depleted marrow exhibited a mixed blood chimerism. This mosaicism was observed before graft failure or relapse in six patients. However, in five other patients, this mixed chimerism was not followed by these complications with a follow-up of 9 to 31 months after transplantation. Our results support the hypothesis that transplanted bone marrow T cells may help to maintain engraftment by eliminating host cells that can cause graft failure.

Adult↗
PubMed1986

Pulmonary complications occurring after allogeneic bone marrow transplantation. A study of 130 consecutive transplanted patients.

This report deals with 81 pulmonary episodes occurring in 130 consecutive patients who underwent allogeneic bone marrow transplantation for hematologic malignancy in the same unit over a 5-year period. These episodes observed in 69/130 patients (53%) were mostly of infectious origin, and were investigated by bronchoalveolar lavage (BAL). The main causes of pneumonia were: cytomegalovirus (CMV) (n = 25), bacterial pneumonia (n = 17), invasive aspergillosis (n = 11) and pulmonary hemorrhage (n = 9). The overall mortality due to or associated with pneumonia was 26/130 (20%). Graft-versus-host disease clearly increased the incidence of infectious pneumonia and the mortality due to or associated with pneumonia. Granulocyte transfusions did not influence the incidence of CMV pneumonitis. The main causes and risk factors for pneumonia are discussed. The role of BAL as a noninvasive procedure is stressed.

Adolescent↗
PubMed1986

HLA-DR restriction in suppression of hematopoiesis by T cells from allogeneic bone marrow transplants.

Three allogeneic bone marrow transplantation patients who exhibited a suppressive subset of T cells for in vitro hematopoiesis have been investigated to determine whether this T cell suppressive effect was genetically restricted. In the three cases, T cells separated by sheep red cell rosetting inhibited blood colony-forming units granulocyte-monocyte (CFU-GM) and burst-forming unit erythroid (BFU-E) growth from the patients and from the bone marrow donors who were HLA identical, but not from randomly chosen unrelated subjects. In one case, cocultures were performed between the patient T cells and the T-depleted cells from eight siblings and from the mother. A marked inhibition (30 to 60%) of CFU-GM and BFU-E growth was found in the relatives who shared a haplo-identical HLA-DR 5. The same degree of suppression was found with respect to whether the siblings were homozygous or heterozygous for the HLA-DR 5 antigen, and whether or not they shared common class I antigens. This inhibition was totally abolished when a monoclonal antibody against HLA-DR was added, whereas a monoclonal antibody against class I histocompatibility antigen had no effect. To additionally demonstrate that this inhibition was mediated by a single HLA-DR haplotype, T cells from the patient were co-cultured with cells from three normal unrelated individuals, one with a phenotypically identical DR and two with only one haploidentical DR. Inhibition was similarly found in the subject exhibiting complete DR identity, and the subject with only the DR 5 haploidentical phenotype. These results demonstrate that a unique subset of T cells present in allogeneic bone marrow transplants specifically suppress differentiation of hemopoietic progenitors that bear one phenotypically haplo-identical HLA-DR antigen.

Adult↗
PubMed1986

Large granular lymphocytes in bronchoalveolar lavage fluids from immunocompromised patients with cytomegalovirus pneumonitis.

Natural killer (NK) cells activities had been demonstrated to be depressed in patients with fatal cytomegalovirus (CMV) pneumonitis. NK cells can be identified by morphologic features characteristic of large granular lymphocytes (LGLs). Bronchoalveolar lavage (BAL) cells from 16 immunocompromised patients with CMV pneumonitis were analyzed. Two different groups of patients could be distinguished depending on the course of the CMV pneumonitis: nine patients who recovered (Group A), seven patients with a fatal outcome (Group B). Except for the increase in polymorphonuclear cells (PMN) in Group B (12.4 +/- 11.6%), no significant difference in the macrophage or the total lymphocyte population was observed. A differential count excluding alveolar macrophages specified the percentage of LGLs from the total lymphocyte population. The LGLs in Group A (7.1 +/- 9.9%) were similar to those previously reported in normal lung. A significant increase in LGLs was observed in the BAL cells from patients of Group B (28.1 +/- 22%). The discrepancy between the high percentage of LGLs in patients with a fatal outcome and their expected protective effects is discussed.

Bronchi↗
PubMed1986

A possible predictive test for graft-versus-host disease in bone marrow graft recipients: the mixed-epidermal cell-lymphocyte reaction.

The possible ability of the mixed-epidermal-cell-lymphocyte reaction (MECLR) to detect alloreactivities in HLA-identical MLR negative siblings has been investigated before grafting in 30 donor-recipients pairs and their families. Results indicate that recipients' epidermal cells (EC) can induce proliferative responses of HLA-identical MLR-negative donors' lymphocytes in 55% of the pairs tested. Moreover, further evaluation of 21 patients shows that the positivity of the MECLR before the graft is correlated with later appearance of acute and chronic GVHD, and especially with the severity of cutaneous injury. EC have been shown to be more efficient antigen presenting cells than peripheral blood lymphocytes for in vitro primary proliferative responses, so these reactions could be directed against some minor histocompatibility antigens, thus leading to possible improvement in selecting bone marrow graft donors and to the detection of donor-recipient pairs with a high risk of GVHD.

Adolescent↗
PubMed1986

[Disseminated aspergillosis in acute leukemia probably chemically-induced].

One case of invasive aspergillosis in patient with myeloblastic leukemia probably induced by chimiotherapy is reported. Aspergillosis is a severe infection in immunodepressed host with 70 to 80% of mortality. Early diagnosis can be often carried by broncho-alveolar lavage, route of entry is always pulmonary one. Rapidly established antimycotic treatment can avoid death. Laminar air flow rooms and air spores numeration allow prevention of this infection in the immunodepressed host.

Adult↗
PubMed1986

Mixed epidermal cell-lymphocyte reaction in prediction of acute graft-versus-host disease in bone marrow recipients.

Peripheral blood lymphocytes (PBL) and epidermal cells (EC) of 44 patients to be grafted with bone marrow from an HLA-identical sibling have been used as stimulator cells in primary cultures with effector PBL of one or several potential donors. Proliferative responses against PBL did not differ from those obtained with effector cells cultured in medium alone, whereas EC induced clearly positive proliferation in 21/53 (40%) of the pairs tested. Evaluation of 30 patients followed for more than 3 months after the graft shows that a high level of response in the mixed epidermal cell lymphocyte reaction is directly correlated with the incidence of acute graft-versus-host disease.

Acute Disease↗
PubMed1986

Clonal T-cell colony formation in agar culture: an attractive assay to test the T-cell depletion from bone marrow.

Current studies suggest that the depletion of T-lymphocytes from donor marrow is an effective method for preventing acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation in man. To deplete the T-lymphocytes from bone marrow cells we use either monoclonal anti-T-cell antibodies and complement or T101 ricin A-chain immunotoxin. Residual T-lymphocytes are analyzed by their capacity to form clonal T-cell colonies in the presence of phytohemagglutinin (PHA), accessory cells, and recombinant interleukin 2. The method is compared to immediate indirect immunofluorescence (iF) and thymidine incorporation by marrow cells stimulated by PHA. IF is not suitable for evaluating the depletion by immunotoxin, and the interpretation of thymidine incorporation is generally questionable. The results of the colony formation show that the sensitivity of the colony assay is close to that of iF when T cells are depleted by complement lysis, and the sensitivity of the colony assay is not dependent upon the depletion procedure. Therefore, the T-cell colony assay is a simple functional control for the quality of bone marrow T-cell depletion, especially for T-cell depletion by immunotoxin.

Agar↗
PubMed1986

[Infections of the central nervous system in malignant hemopathies].

Central nervous system (CNS) infections in immunocompromised hosts are often accompanied by subtle disorders because immunosuppression usually decreases the inflammatory response. CNS infections in immunocompromised patients are usually caused by organisms different from those found in the general population. The organism causing CNS infection in an immunocompromised host can often be predicted if the type of immune abnormality of the patient is known. The common causes of CNS infection in immunocompromised hosts are reviewed here. Meningitis in patients with neutropenia is usually due to enteric Gram negative bacilli that live in the patient's own digestive tract. Pseudomonas aeruginosa is most common and is followed by E. Coli, Klebsiella, Enterobacter and Proteus. A major risk in patients with abnormal immunoglobulins or splenectomy is infection with encapsulated bacteria, particularly Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis. Meningitis caused by any of the encapsulated bacteria can be fulminant. Listeria monocytogenes is the most common cause of bacterial meningitis in patients with impaired cellular immunity. Nocardia asteroides is a leading cause of brain abscess in patients with hematologic malignancy. Most patients have evidence of concomitant pulmonary lesions. Fungi are among the most common organisms involving the CNS in immunocompromised hosts. Susceptible patients include those with lymphoma or leukemia and those who receive therapies aimed at suppressing delayed hypersensitivity. Cryptococcus neoformans is a common fungal cause of CNS infection in immunocompromised hosts. The primary site of infection is the lung. Spread to the CNS is via the blood stream. The clinical course is highly variable: meningitis, meningoencephalitis and focal mass lesions. Candida causes meningitis or meningoencephalitis characterized by multiple small abscesses in neutropenic hosts. Organisms reach the CNS via the blood stream usually from the digestive tract or infected intravenous catheters. Aspergillus causes brain abscess, cerebral infarction and focal meningitis in patients with neutropenia. The primary infection is in the lung. The parasites that infest the CNS of immunocompromised patients are usually those that exploit a T-lymphocyte, mononuclear phagocyte host defect. The most common are Toxoplasma gondii and Strongyloides stercoralis. There have been a few cases of amebiasis with dissemination to the brain in patients with hematologic malignancies. Toxoplasma gondii causes major CNS disease in immunocompromised hosts: meningoencephalitis or mass lesions.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacterial Infections↗
PubMed1985

Acute promyelocytic leukemia in 57 previously untreated patients.

Fifty-seven patients in initial phase of acute promyelocytic leukemia (APL) were treated in the same department with heparin infusion, platelet transfusions, and two related induction regimens both including cytosine arabinoside and daunorubicin. Clinical and biological findings at presentation were studied. The complete remission (CR) rate was 53%. Twenty-seven patients (47%) died during the initial course of the disease, either before day 5 (early death [ED], n = 7) or after day 5 (death in aplasia [DA], n = 20). Most ED was due to intracerebral hemorrhage (6/7), especially when large hemorrhages had been seen on fundus oculi examination. Most DA was due to multivisceral failure (9/20). No correlation was found between initial disseminated intravascular coagulation (DIC) and death. However, the worsening of coagulation parameters during induction therapy, with or without initial DIC, significantly increased the occurrence of renal and respiratory failure which were particularly frequent during the first month. The median duration of survival was short (3.5 months) and the median duration of CR (11 months) was similar to that of other acute myeloid leukemias treated with the same regimens. The possible causes of the high mortality observed during the initial courses of APL and the possible benefit of a more graduate induction chemotherapy are discussed.

Acute Kidney Injury↗