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Biomedical subjects

J Földi

Publications and source records attributed to J Földi.

At least 19 recordsLinked to original sources

Bacterial complications of postpartum uterine involution in cattle.

The bacterial contamination of the postpartum uterus is a frequent finding which by itself does not disturb the anatomical and histological restoration of tubular genital tract. The improper balance between uterine infection and the intrauterine antimicrobial self-defence mechanisms, however, often results in complications, such as puerperal metritis, clinical endometritis, pyometra and subclinical endometritis. After reviewing the bacteriology of uterine involution, and the predisposing factors for its bacterial complications, this paper defines the different clinical forms, and summarizes their pathology, furthermore, the recent progress in diagnostic considerations and principles of current treatments for these diseases of bovine genitals.

Animals↗

Equid herpesvirus (EHV-1) live vaccine strain C147: efficacy against respiratory diseases following EHV types 1 and 4 challenges.

The temperature sensitive and host range mutant clone 147 of equine herpesvirus 1 (EHV-1) was assessed for its ability to protect conventional, susceptible adult horses against respiratory infection by EHV-1 and equine herpesvirus 4 (EHV-4). Intranasal (IN) vaccination with 5.2 log(10) TCID(50) did not cause adverse clinical reactions although a limited virus shedding and viraemia (leukocytes) was observed in 11 of 15 and 10 of 15 vaccinated horses respectively. All 15 vaccinated horses showed a significant seroresponse to both EHV-1 and EHV-4 for virus neutralising (VN) antibody. None of 14 control horses shed virus or became viraemic or seroconverted prior to challenge. EHV-1 challenge (dose 6.0 log(10)) 6 weeks after vaccination resulted in pyrexia in all eight control horses while eight vaccinated horses remained unaffected. Six control horses developed nasal discharge, five of which were mucopurulent nasal discharge (mean duration 3.2 days) which also occurred in four vaccinated horses for 1 day. All eight control horses shed challenge EHV-1 at a significantly higher level (group mean titre 2.6+/-0.4 log(10) TCID(50) per sample) and for much longer (mean duration 4.8+/-1.5 days) than that (group mean titre 1.4+/-0.8 log(10) TCID(50) per sample and mean duration 1.5+/-0.5 days) in six vaccinated horses. Furthermore, all eight control horses became viraemic (mean duration 2.9 days) but viraemia did not occur in eight vaccinated horses. Following EHV-1 challenge, all eight control horses showed a significant VN antibody rise to both EHV-1 and EHV-4 but this occurred in only one vaccinated horse and to EHV-4 only. In EHV-4 challenge (dose of 4.2 log(10) TCID(50)) of a separate pair of seven vaccinated and six control horses, 6 weeks after EHV-1 vaccination resulted in pyrexia (mean duration 2.3 days) and nasal discharge (mean duration 1.8 days) in three and five control horses respectively but the only reaction observed in the vaccinated group was nasal discharge for 1 day in one animal. All six control animals shed virus (mean titre 2.5+/-0.6 log(10) TCID(50) per sample and mean duration 2+/-0.6 days) compared to one vaccinated animal. Although EHV-4 viraemia is rare, 3 of 6 control horses became viraemic after EHV-4 challenge but this was not observed in vaccinated horses. After EHV-4 challenge 3 and 5 of 6 control horses seroconverted for VN antibody to EHV-1 and EHV-4 respectively; a non-responsive control horse had high level of pre-existing VN antibody to EHV-4. However, only 1 of 7 vaccinated horses showed a significant antibody rise and only to EHV-4.

Administration, Intranasal↗

Acute myeloid leukaemia of donor cell origin developing 5 years after allogeneic bone marrow transplantation for chronic myeloid leukaemia.

We report the case of a male patient with Ph-positive CML who developed AML 5 years after allogeneic BMT. Clinically, the AML seemed to develop on the basis of a myelodysplasia. The myeloid origin of blasts has been proven by immunophenotyping. The variable number of tandem repeats (VNTRs) and short tandem repeat (STR) showed donor-type haemopoiesis. The interphase FISH showed the XX genotype directly in the morphologically identifiable blasts and in the CD34-positive sorted bone marrow cells. This proved the new leukaemia to be of donor origin. The necessity of using multiple techniques and the advantage of combined immunophenotyping and FISH methods in this case is emphasized.

Acute Disease↗

[Role of molecular genetic investigations in the diagnosis of acute leukemias and in the detection of minimal residual disease].

Chimera gene products, the molecular hallmark of acute leukemias were detected and quantified for diagnostic purposes and for follow up of therapy and characterization of minimal residual disease. In acute lymphoid leukemia mainly the bcr-abl, and in acute myeloid leukemias, depending on the morphological classification, the aml-eto, bcr-abl, pml-rara, plzf-rara, and cbfb-myh chimeras were investigated. The determinations were based on reverse transcriptase-polymerase chain reaction. The results were used in diagnosis of 315 new leukemic patients, and in follow up of 70 ones. In the present paper the usefulness of the applied methods is illustrated by presentation of data of 38 (27, acute myeloid leukemias and 11 acute lymphoid ones) patients out of the 139 treated in the National Institute during the last years.

Acute Disease↗

Remarkably reduced transplant-related complications by dibromomannitol non-myeloablative conditioning before allogeneic bone marrow transplantation in chronic myeloid leukemia.

A non-myeloablative conditioning protocol containing dibromomannitol (DBM/cytosine arabinoside/cyclophosphamide) has been applied to 36 chronic myeloid leukemia (CML) patients followed by bone marrow transplantation (BMT) from sibling donors. Risk factors include: accelerated phase (10 patients), older age (17 patients over >40 years) and long interval between diagnosis and BMT (27 months on average). Severe mucositis did not occur. Venoocclusive liver disease was absent. Infectious complications were rare. Although grade II-IV acute graft-versus-host disease (GVHD) was present in 9 (25%) cases, there were only 2 serious (III-IV) ones. Chronic GVHD occurred in 25 (69%) cases, preceded by acute GVHD in 9 of the 25 affected patients. Early hematological relapse, 7-29 weeks after BMT, developed in 6 patients (17.6%). No relapse was noted in the completely chimeric patients, however molecular genetic residual disease was observed in 6 patients, in most of them after transient short-term mixed chimeric state. Overall actual survival rate is 83.3% for the 36 cases, and leukemia-free survival is 72.2% for the 34 engrafted patients.

Adolescent↗

[Autologous hematopoietic stem cell transplantation in chronic myeloid leukaemia with different clinical stages]

For most chronic myeloid leukaemia patients the option of a potentially curative allogeneic stem cell transplantation is not available because of age or lack of donor. Alternative therapy with interferon-alpha appears to prolong survival but is probably not curative. The aim of the study is to analyse the clinical results of the first Hungarian autologous transplantations in CML. METHODS: Seven patients were treated with ICE-based regimen plus G-CSF with the aim of mobilising and collecting Ph-negative peripheral stem cells in the setting of autologous transplant program. Five patients had CML in first chronic phase and two in accelerated phase. All patients have been previously treated with interferon-alpha. RESULTS: Median value and ranges for harvested mononuclear cells, CD34(+) cells and CFU-GM were: 5.65x10(8)/kg (2.61-11.38), 1.48x10(6)/kg (0.216-3.5) and 3.43x10(4)/kg (0.243-11.6), respectively. Four out of seven autologous grafts have been transplanted. Busulfan conditioning was used in one case and TBI/Cy conditioning in three patients. All patients are alive and well post-transplant being on interferon-alpha therapy. CONCLUSIONS: Based on the clinical advantages of autologous transplantation including long-term chronic phase, achievement of second chronic phase and improved response to interferon-alpha therapy, the procedure can offer an alternative treatment in CML in lack of HLA-identical donor.

Journal Article↗

[Clinical and immunopathological significance of chimerism in bone marrow and organ transplantations]

Chimerism is an exceptional immunogenetic state, characterized by the survival and collaboration of cell populations originated from two different individuals. The prerequisites to induce chimerism are immunosuppression, myeloablation or severe immunodeficiency of the recipients on one side and donor originated immuno-hematopoietic cells in the graft on the other. Special immunogenetic conditions to establish chimerism are combined with bone marrow transplantation, transfusion and various kinds of solid organ grafting. There are various methods to detect the type of chimera state depending on the immunogenetic differences between the donor and recipient. The chimera state seems to be one of the leading factors to influence the course of the post-transplant period, the frequency and severity of graft-versus-host disease (GVHD), and the rate of relapse. However, the most important contribution of the chimeric state is the development of graft versus leukemia (GVL) effect. A new conditioning protocol (DBM/Ara-C/Cy) for allogeneic BMT in CML patients and its consequence on chimera state and GVL effect is demonstrated.

Journal Article↗

[Immunophenotyping in acute leukemia: detection of minimal residual disease].

Immunophenotyping improves both accuracy and reproducibility of the acute leukaemia classification and is considered particularly useful for identifying poorly differentiated subtypes of acute myeloid leukaemia and lineage association of acute lymphoid leukaemia. Immunological studies of leukaemic blasts has become critical also identifying biphenotypic leukaemias and acute myeloid leukaemia expressing lymphoid associated markers. At present, while the prognostic value of individual antigen expressions is still controversial, the immunologic detection of minimal residual disease seems to be important in monitoring the acute leukaemia patients in remission. In the present study immunophenotyping of bone marrow samples of 42 patients with acute myeloid leukaemia and 13 patients with acute lymphoid leukaemia was analysed. Patients were assessed both before and after treatment by immunophenotyping, cytogenetics and polymerase chain reaction amplification. The immunophenotyping have allowed more sensitive definition of acute leukaemia relapse, but molecular genetic methods are recommended for detection of elimination of residual disease.

Adolescent↗

[Detection of minimal residual diseases in B-cell tumors using PCR specific for the immunoglobulin heavy chain gene].

In B-cell non-Hodgkin's lymphomas (NHL), clonal rearrangement of the immunoglobulin heavy chain (IgH) gene provides a useful marker for the detection of minimal residual disease (MRD) after treatment. To explore clinical usefulness of polymerase chain reaction (PCR) analysis of clonal IgH gene rearrangement in the detection of MRD a follow up study of 10 patients with B-cell NHL have been performed. At the time of diagnosis, tumor DNAs were PCR-amplified using sense primer specific for the heavy chain variable region (VH) and antisense primer specific for the heavy chain joining region (JH) of the IgH gene. The clonal rearrangement of IgH gene detected by PCR was used as clonal marker to determine MRD after treatment. In three cases, where clinical remission was not achieved, clonal IgH gene rearrangement was detected after the treatment. In seven cases, clinical remission was achieved after induction therapy but the PCR analysis revealed clonal IgH gene rearrangement in three of the cases. In all of the three cases, where MRD was detected by PCR, clinical relapse developed after 7-28 months of the therapy. In all cases that have relapsed, the IgH gene rearrangement was identical at the time of initial diagnosis and at the relapse. This study demonstrates that PCR analysis of clonal IgH gene rearrangement is a useful method to monitor and detect MRD before clinical relapse.

Biomarkers, Tumor↗

Immunological importance of chimerism in transplantation: new conditioning protocol in BMT and the development of chimeric state.

Chimerism is an exceptional immunogenetic state, characterized by the survival and collaboration of cell populations originated from two different individuals. The prerequisits to induce chimerism are immuno-suppression, myeloablation, or severe immunodeficiency of the recipients on the one side and donor originated immuno-hematopoietic cells in the graft on the other. The pathologic or special immunogenetic conditions to establish chimerism are combined with bone marrow transplantation, transfusion, and various kinds of solid organ grafting. Different types of chimerism are known including complete, mixed and mosaic, or split chimerism. There are various methods used to detect the type of chimera state, depending on the immunogenetic differences between the donor and recipient. The induction of complete or mixed chimerism is first determinated by the effect of myeloablative therapy. The chimera state seems to be one of the leading factors to influence the course of the post-transplant period, the frequency and severity of GVHD, and the rate of relapse. However, the most important contribution of the chimeric state is in development of graft versus leukemia effect. A new conditioning protocol (DBM/Ara-C/Cy) for allogeneic BMT in CML patients and its consequence on chimera state and GVL effect is demonstrated.

Antineoplastic Agents, Alkylating↗

Detection of a b3a3 type chimera in chronic myeloid leukemia by double hybridisation of RT-PCR products.

The standard RT-PCR method performed on RNA of a chronic myeloid leukemia patient resulted in a product of unusual size. Hybridisation to a probe containing the a2 sequences yielded a very faint band. Rehybridisation of the same blot to b3 sequences has given a firm signal. Based on the size of the product and on results of hybridisation tests, a translocation, resulting in a b3a3 juxtaposition, was supposed. The direct sequencing of the RT-PCR product has proven this hypothesis. We concluded, that double hybridisation of RT-PCR products of standard methods is a useful tool in detection of rare bcr-abl chimeras.

Female↗

[Use of studies on genome polymorphism in follow up after allogenic bone marrow transplantation].

The study of structures polymorphic in size found in the human genom (the VNTR loci) enables us to differentiate two individuals or--after bone marrow transplantation--to detect the simultaneous presence of two genoms in patients' blood or marrow. The existence of mixed chimerism may influence the therapy. The authors have screened 54 patients, transplanted in their Institute, and their donors by determination of four polymorphic loci. Informative marker was found in 43 cases. The bone marrow transplantation immunotherapy of 29 patients could be followed over 2-36 months. To increase the sensitivity of the polymerase chain reaction method used, the authors introduced the blotting/hybridization steps using isotop labeled repetitive sequences. The results are presented in comparison with literature data.

Bone Marrow Transplantation↗

[A new radiation-free conditioning in bone marrow transplantation and dibromo-mannitol therapy in chronic myeloid leukemia].

A new, radiation-free, conditioning protocol, containing the original Hungarian mitobronitol (DBM) (DBM/ cytosine arabinoside/cyclosphosphamide) has been applied to 36 chronic myeloid leukemia (CML) patients followed by bone marrow transplantation (BMT) from HLA identical sibling donors between 1990-1997. In spite of some prognostically disadvantageous factors (half of them were above 40 years, 10 out of 36 patients were in accelerated phase, the disease history was longer than 2 years in average) the overall survival (30/36) and the leukemia free survival rate (26/36) were in accordance with the best international results. Transplantation-related toxicity was remarkably reduced in comparison to bone marrow transplantation performed by total body irradiation/cyclophosphamide (TBI/Cy) or busulphan/cyclophosphamide (Bu/Cy) conditioning protocols. Acute graft versus host disease was present in lower percentage (9/36) and the number of serious cases was only 2/36. Chronic GVH disease, generally known to be associated with antileukemic effect (GVL), occurred in 25 of cases. Early haematological relapse among the 34 patients with functioning graft occurred in 6 patients which rate is slightly higher than reported after TBI/Cy or Bu/Cy conditioning treatment. There was no relapse among patients transplanted within one year post-diagnosis and patients having CML with accelerated phase. The leukemia free post-transplant period was in association with the chronic GVH disease and full chimeric state.

Adolescent↗

[Study of low density lipoprotein (LDL) receptor mutations, using restriction endonucleases, in familial hypercholesterolemia].

Familial hypercholesterolemia (FH) is an autosomal dominant metabolic disorder caused by different mutations in the low density lipoprotein receptor (LDLR) gene. We analyzed 13 families (23 patients) with FH and 36 subjects with normocholesterolemia by restriction fragment polymorphism (RFLP) using enzymes Xbal, BgIII and PvuII. At the 3' end of LDLR an extra 4.4 kb band has been found by Xbal digestion in one patient and it has been proved to be a "de novo" form of mutation. In the 5' end of LDLR gene a combined mutation has been identified in two FH families. The Xbal RFLP has yielded an extra band of 24.5 kb and an another extra band of 17.5 kb has been found by BgIII digestion. It has been suggested that the simultaneous occurrence of 3.3 kb extended deletion (intron 3) and 4.8 kb extended insertion (intron 1) is present. In our study the frequency of P2 allele (PvuII RFLP) in FH patients did not differ from normocholesterolemic controls.

Adolescent↗

Lymphocyte subset reconstitution after allogeneic bone marrow transplantation using radiation-free conditioning regimen for patients with chronic granulocytic leukemia.

Conditioning regimens for BMT are important in determining transplant outcome. A radiation-free protocol containing Mitobronitol (DBM), Cytarabine (Ara-C) and Cyclophosphamide (Cy) was used for conditioning of patients with chronic granulocytic leukemia (CGL). Using this conditioning treatment, fewer transplant related complications, including acute GVHD, VOD and severe infections, were observed. Acute GVHD did not develop, but chronic GVHD, accompanied with graft-versus leukemia, was present in half of the cases. To determine the clinical effect of the DBM/Ara-C/Cy conditioning, the recovery of peripheral blood lymphocytes was examined after allogeneic BMT for patients with CGL in comparison with TBI/Cy conditioning. The lymphocyte subsets of 11 DBM patients were followed and analyzed periodically (30-90 days, 4-12 months and > 13 months) using ten monoclonal antibodies and flow cytometry. Decreased percentage of total T cells as well as CD4+ and CD8+ subpopulations, significantly decreased T cell activation and increased proportion of TCR gamma delta + cells were found to be characteristic in the early post-transplant period in the DBM group. Early recovery and consistently higher percentage of B cells were observed for the whole follow-up period of patients receiving DBM conditioning. A high proportion of NK cells was observed in all transplant recipients. These findings suggest that the characteristic pattern of recovering lymphocytes is associated with the lack of severe transplant-related clinical complications following DBM/Ara-C/Cy conditioning.

Adolescent↗

[Experience with the molecular genetical detection of the chimera gene of the Philadelphia chromosome].

Molecular genetical techniques could be developed for detection of the chimera gene of Philadelphia chromosome or that of its gene product, due to the relatively conserved structure of the chimera gene. The authors successfully analysed 123 blood/bone marrow samples from 106 patients using these molecular techniques adapted from the literature. Patients were classified by the first diagnosis, 65 CML, 7 AML, 13 ALL patients were studied. 12 patients had the diagnosis of myeloproliferative syndrome, and 9 patients were after bone marrow transplantation. 57% of the total, and by diagnosis, 74% of CML, 28% of AML, 54% of ALL, and 33% of post-transplant samples have shown the chimera gene structure characteristic for Philadelphia chromosome. All patients of myeloproliferative syndrome were negative. In some cases the authors had the opportunity to study simultaneously the peripheral blood and the bone marrow sample of the same patient and of the same date. The ratio of the positivity of the two samples varied from one to infinite. The authors could follow the effect of interferon in one case, the change of clonality of the leukemic cell line in an other case. They had the opportunity to detect two different abnormal gene structures in the sample of an AML patient.

Chimera↗