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Biomedical subjects

M Manna

Publications and source records attributed to M Manna.

33 records · Page 2Linked to original sources
PubMed1986

Fetal to adult hemopoietic cell transplantation in humans: insights into hemoglobin switching.

A 2-year-old boy with refractory acute leukemia (ALL) was transplanted with liver cells from twin fetuses of an 18-gestational-week age. Regeneration of hemopoietic cells was evident during the second week following transplantation when a cellular, predominantly erythroid, marrow was present. Studies of bone marrow and peripheral blood cells obtained 21 days posttransplant showed that bone marrow and peripheral blood BFU-E-derived erythroblasts displayed typical fetal patterns of globin chain synthesis (gamma/gamma + beta ratios: 0.87 to 0.98). In addition, all of the individually analyzed erythroid clones displayed a fetal type of globin program, suggesting that the presence of rare, partially switched clones was unlikely. Additional evidence supported the fetal phenotype of these progenitors. The il expression of culture-derived erythroblasts was typical for fetal erythroid cells. As in fetal cells, fetal sheep serum influenced neither the globin nor the il phenotypes, and the growth characteristics were as those observed in fetal liver cultures. That these fetal progenitors matured in vivo and produced cells with a fetal program was shown by the pattern of globin biosynthesis in bone marrow cells and peripheral blood reticulocytes (gamma/gamma + beta ratios: 0.85 to 0.95) at days 14 and 21 posttransplantation. These results indicate that the transplanted fetal cells, in spite of their proliferation and differentiation in the environment of the recipient, continued to express during the early posttransplantation period fetal patterns of globin, surface antigenic determinants, and growth and response to environmental modulation. The observations in this patient support the notion that hemoglobin switching is primarily controlled by a mechanism intrinsic to the stem cell.

Bone Marrow↗
PubMed1985

Marrow transplantation for thalassaemia following busulphan and cyclophosphamide.

30 patients with homozygous beta-thalassaemia aged 6 months to 7 years received allogeneic marrow transplants following busulphan (Bu) and cyclophosphamide (Cy). Post-transplant immunosuppression was with methotrexate (MTX) or MTX and Cy. The first 6 patients received 16 mg/kg Bu and 200 mg/kg Cy. 3 died of transplant-related complications and 3 survived without thalassaemia 701-762 days after transplantation. The subsequent 24 patients received 14 mg/kg Bu and 200 mg/kg Cy. 1 died on day 28 without engraftment and 23 survived 64-624 days after transplantation. 19 of the 23 surviving patients are without thalassaemia while 4 patients with initial engraftment became thalassaemic again in 32-46 days and survived 253-624 days after transplantation. The latest death was 50 days after transplantation. The probability of developing grade 2 or greater acute graft versus host disease (GVHD) in patients with sustained engraftment was 23%. 5 patients had chronic GVHD which is still active and causing disability in 3 patients 358, 456, and 477 days after transplantation. The actuarial survival was 86% and the actuarial disease-free survival was 73%.

Actuarial Analysis↗
PubMed1985

Fetal liver transplantation in the mini-pig.

After the characterisation of the hematological and immunological status of the mini-pig fetus at different gestational ages of development was performed, two different groups of animals receiving 800 rads of TBI given by a radioactive cobalt source at a dose/rate of 5/6 rad/min or 750 rads of TBI given by a Linear Accelerator at a dose/rate of 25/26 rad/min, both in a single dose exposure, were transplanted with a pool of allogeneic fetal liver cells whose age ranged between 55 and 75 days of gestation. In the first group 1 animal out of 6 is alive and well 30 months post-transplant. In the second group one of the nine transplanted animals survived 78 days. Engraftment was proved by the presence of the donor chromosome in the proliferating bone marrow cells in one animal.

Animals↗
PubMed1984

Allogeneic marrow transplantation for thalassemia.

Thirteen patients with homozygous beta thalassemia underwent allogeneic marrow transplantation from sibling donors, 12 of whom were heterozygous for beta thalassemia. Six patients were transplanted in an advanced stage of their disease while seven were transplanted early in their disease course. Donors and recipients were genotypically identical for the HLA-A, -B and -D loci in 11 cases and mismatched for the D locus in two. A variety of preparative regimens was utilized involving high doses of busulphan (Bu) and/or cyclophosphamide (CY) and/or total body irradiation (TBI). Failure of engraftment or autologous hematologic recovery after transient engraftment was seen after intensive preparative regimens including: CY 200 mg/kg and 800 rad of TBI; Bu 8 mg/kg and CY 200 mg/kg; and Bu 8 mg/kg, CY 200 mg/kg, and 300 rad of TBI. A regimen of Bu 16 mg/kg, CY 200 mg/kg, and 400 rad of TBI resulted in deaths from transplant-related causes in the three patients treated with this regimen. Seven of the 13 patients are surviving 363-665 days after transplant. Five of the seven failed to achieve engraftment or had autologous reconstitution after transient engraftment. Five of the six deaths were transplant related, and one patient died of cardiac failure one year after an unsuccessful transplant attempt. Two patients are surviving with engraftment and without thalassemia major 363 and 491 days after transplantation. Both of these patients were transplanted early in their disease course.

Adolescent↗
PubMed1983

Ontogeny of granulocyte-macrophage progenitor cells in the human fetus.

The CFU-Gm content of liver, spleen and bone marrow of human fetuses was determined from the 8th to 28th week of gestational age. The study of progenitor cells from 43 fetal livers revealed that the CFU-Gm increased from 8 to 12 weeks, was relatively stable through 16 weeks and thereafter declined by 22 to 24 weeks. The total number of liver CFU-Gm rose from 10(4) to greater than 10(6) CFU-Gm by the 16th week of gestation and declined to approximately 4 X 10(5) progenitor cells by 22 to 24 weeks. Peak values of bone marrow CFU-Gm were noted at 10 to 14 weeks of gestation. Generally, the numbers of these progenitor cells declined by 16 to 18 weeks; however, several high values were obtained at later times. Splenic CFU-Gm were relatively constant in number between 12 and 28 weeks of gestation with no correlation with fetal age. Thus, these studies indicate that certain fetal tissues contain substantial numbers of hemopoietic progenitor cells. Based on the quantity of CFU-Gm obtained, it appears feasible to use fetal liver cells as a source of progenitor cells for transplantation.

Bone Marrow↗
PubMed1982

Fetal liver transplantation in 2 patients with acute leukaemia after total body irradiation.

2 patients with acute leukaemia in relapse were transplanted with fetal liver cells following a conditioning regimen of cyclophosphamide (120 mg/kg) and total body irradiation (1000 r). Each patient achieved a remission with haematopoietic recovery that was rapid in one case and delayed in the other. In one case there was evidence of chimerism as demonstrated by the presence of the XYY karyotype of the donor fetus in 20% of marrow metaphases, by the presence of double Y bodies in the peripheral blood, by the appearance of new HLA-antigens, and by red cell isoenzyme phenotypes of donor origin. In the second case there was prompt haematopoietic recovery and the appearance of red cell isoenzyme phenotype of donor origin. Survival was 153 and 30 d, respectively, and both patients died of interstitial pneumonia without evidence of graft versus host disease.

Acute Disease↗
PubMed1981

Transplantation of fetal liver of different ages in the rat.

This study investigates the effect of fetal liver transplantation in reconstituting hemopoiesis in supralethally irradiated rats. Different cell doses of fetuses at the embryonic age of 15 and 18 days were compared to equivalent cell doses of adult bone marrow cells. Although the frequency of engraftment ranged between 75 and 100% in all the groups of animals studied, the survival rate at 30 days after TBI did not show any significant difference between the fetal liver and the bone marrow treated recipients. The bone marrow transplants performed in littermate rats almost doubled the percentage of survivors at 30 days and showed a cell dose relationship suggesting that, in the closed colony of random-bred rats used, the mortality after bone marrow and fetal liver transplants was mainly due to graft-versus-host-disease. Antibiotic prophylaxis and treatment during the experiment did not modify the results in a separate group of fetal liver and bone marrow transplanted rats. In the rat model system used in this set of experiments fetal liver did not reveal any advantage over bone marrow transplantation.

Animals↗
PubMed1981

[The use of autologous bone marrow transplants in malignant hemopathies and solid tumors].

Bone marrow collected from patients with hematologic malignancies were cryopreserved using DMSO as a cryoprotective agent. The growth kinetics of hemopoietic stem cells frozen to -196 degrees C were monitored immediately after thawing by the semisolid agar CFU-C assay and 2 different methods of cell reconstitution were compared. In the first way, thawed cells were plated after the removal of DMSO by washing the cell suspension, in the second, cell suspensions were cultured after a simple 1:1 dilution of DMSO with medium. The number of CFU-C per 2 X 10(5) cells plated was higher washing out the DMSO in all the groups studied. However, the absolute numbers of CFU-C contained in the whole ampoules after the freezing procedures was approximately the same with both methods. It is concluded that washing the cells only apparently yielded a better cloning efficiency, suggesting that such a procedure led to a higher mature nucleated cell loss with the consequence of a CFU-C concentration. This trend seems particularly evident in the AML and CML patients.

Bone Marrow Transplantation↗
PubMedDate not supplied

Molecular analysis of HLA class II antigens in bone marrow transplanted thalassemic patients.

BACKGROUND: In this work we investigated whether serologically HLA class II compatible donor-recipient pairs showed differences in restriction fragment length patterns, and whether there is a correlation between the genomic differences observed and the incidence of rejection and acute graft versus host disease (GVHD). METHODS: High molecular weight DNA was extracted from thirty-three transplanted thalassemic patients and from their genotypically HLA identical donors. The DNA was digested with TaqI and PstI restriction enzymes, separated by horizontal electrophoresis and transferred onto nylon filters. RESULTS: Differences at the molecular level were observed in only one patient, who rejected the transplant respect to his donor when DNA was digested with the TaqI restriction enzyme and hybridized with DPB cDNA probe. CONCLUSIONS: Although the molecular analysis revealed a difference between a patient who rejected the transplant and his donor, the RFLP typing confirmed the serological identity of the HLA class II antigens in all the other donor-recipient pairs studied.

Adolescent↗
PubMedDate not supplied

[Proposal of a thoraco-pulmonary rehabilitation program in patients with chronic obstructive pulmonary disease].

BACKGROUND: The aim of the study was to give guidelines for the management of a pulmonary rehabilitation program in patients affected by COPD. MATERIALS AND METHODS: 52 patients affected by COPD with chronic respiratory failure and hypoxemia have been evaluated. All patients underwent a personalized rehabilitation program joining traditional technics of rehabilitation and an exercise training. The study was divided into three different phases: traditional pulmonary rehabilitation; exercise training by treadmill; home care rehabilitation. In order to follow-up the outcome of the patients, the 12 minutes walking test and the pulmonary function tests were used. RESULTS: The study showed clearly an improvement of fitness of the patients after exercise training These results were confirmed after one year follow-up. CONCLUSIONS: In conclusion, in the light of these results, the exercise training and, overall, the home care rehabilitation, acquire an important role in the management of patients affected by COPD.

Exercise Therapy↗