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PubMed1990

Mixed lymphocyte culture reactivity of fetal baboons: application for in utero bone marrow transplantation.

Bone marrow transplantation offers a potential cure for patients suffering from genetic diseases such as inborn errors of metabolism. The optimal time to transplant many of these affected individuals would be early in gestation. To date, little information is available on the cellular immune reactivity of fetal primate lymphocytes. Therefore, we tested peripheral blood lymphocytes obtained in utero from baboon fetuses (Papio sp.) for their ability to respond in mixed lymphocyte culture (MLC) against their mothers, against a pool of unrelated animals, and in the case of fetuses given unrelated bone marrow transplants in utero, against their specific bone marrow donors. The majority of fetuses as young as 80 gestational days (182-day normal gestation period) were capable of responding strongly to maternal and unrelated lymphocytes in MLC. Of six fetuses that were transplanted, three did not engraft as indicated by undetectable levels of the donor-specific type B allele of glucose phosphate isomerase in fetal blood samples 1 month post-transplant. The three fetuses that did engraft all lost their grafts before birth. These data demonstrate that fetal lymphocytes obtained in utero can be tested for MLC reactivity and suggest that MLC testing can be used to select appropriate donor-recipient combinations for in utero bone marrow transplantation.

Animals↗
PubMed1993

Disseminated intravascular coagulation in a patient with acute myeloid leukemia. Ultrastructural evidence of hypercoagulation in bone marrow.

The bone marrow of a 53-year-old woman with acute myeloid leukemia (AML) with disseminated intravascular coagulation was investigated by transmission electron microscopy. The patient had a preceding granulocytic sarcoma, and subclinical disseminated intravascular coagulation occurred concomitantly with the development of AML. Ultrastructural findings of the bone marrow at the onset of AML revealed the following: (1) The cytoplasm of the leukemic cells showed frequent fragmentation, resulting in the formation of abundant cytoplasmic fragments. (2) These cytoplasmic fragments were surrounded by abundant fibrin fibers, forming the fibrin-cytoplasmic fragment complex (FCF complex). (3) Slight fibrin deposition was seen around the leukemic cells and in the intercellular space of the bone marrow. Fibrin deposition in the bone marrow is thought to represent morphologic evidence of disseminated intravascular coagulation. The damage on the leukemic cell surface due to the cytoplasmic fragmentation seems to be closely related to the development of disseminated intravascular coagulation.

Acute Disease↗
PubMed1996

[Detection of lesions in bone marrow for the diagnosis of miliary tuberculosis: reliability of bone marrow aspiration and biopsy in view of distribution pattern of lesions in autopsy cases].

The usefulness of the serial section method was investigated in four bone marrow aspirates, four biopsies and nine autopsy specimens obtained from patients with miliary tuberculosis who were admitted to our hospital between 1974 and 1994. In original sections, granulomas consistent with tuberculosis were found in two out of four aspirate specimens (50%) but in none of the four bone marrow biopsies. By using serially out sections, however, granulomas were detected in two more aspirate specimens and two biopsies which were negative in original sections. Consequently four of four aspirates (100%) and two of four biopsies ((50%) became positive. In addition, the distribution of granulomas was investigated using vertebral bone marrows obtained from 12 autopsy cases. We divided the vertebral bone marrows obtained from 12 autopsy cases. We divided the vertebra into the peripheral and central portions. Granulomas were more frequently found in the peripheral portions than in the central. The higher detection rate of granulomas in the peripheral bone marrow when the biopsy and aspiration needles easily reach, suggests that bone marrow aspiration and/or biopsy would be a useful procedure for the diagnosis miliary tuberculosis. Therefore if serial sections were utilized for such samples in the miliary tuberculosis patients, the detection rate is expected to became much higher.

Aged↗
PubMed1984

Bone marrow repopulation capacity after transplantation of lymphocyte-depleted allogeneic bone marrow using counterflow centrifugation.

Bone marrow from six allogeneic HLA-matched and MCL nonreactive siblings was fractionated by means of isopycnic flotation centrifugation and subsequent counterflow centrifugation. The low density fraction (d less than or equal to 1.070 g/ml) obtained by IFC contained 20% of the nucleated cells and more than 90% of the myeloid and erythroid progenitors. The putative stem cell fraction obtained by CC showed a satisfactory recovery (88%) of the CFU-GM and BFU-E and only 3.5% of the original number of T lymphocytes. Bone marrow repopulation capacity was not impaired in comparison with a comparable group of patients. Despite the average high age of this group (29.6 years), only one of the four evaluable patients developed graft-versus-host disease.

Adolescent↗
PubMed1985

Effect of natural killer cells on syngeneic bone marrow: in vitro and in vivo studies demonstrating graft failure due to NK cells in an identical twin treated by bone marrow transplantation.

Bone marrow transplantation for severe idiopathic aplastic anemia was undertaken in a patient, using his monozygotic twin brother as the donor. In spite of the use of syngeneic bone marrow, failure of engraftment occurred on two occasions. In vitro studies demonstrated that natural killer (NK) cells from the recipient markedly inhibited the growth of donor bone marrow granulocyte progenitor cells. On a third attempt, successful bone marrow engraftment was achieved following high-dose cyclophosphamide, which has previously been shown to be inhibitory to NK cells. We conclude that NK cell activity may play an important role in bone marrow failure as well as being responsible for at least some cases of aplastic anemia.

Adult↗
PubMed1994

Development of hemopoietic bone marrow within the ectopic bone induced by bone morphogenetic protein.

Neogenesis of hemopoietic bone marrow was observed in the ectopic bone induced by implantation of bone morphogenetic protein (BMP) into the muscle of mice. A bone rudiment-like cartilage was formed first, which was then replaced by bone through an endochondral ossification process. Bone marrow formation occurred after the invasion of blood vessels into the cartilage, with accumulations of small lymphocyte-like cells and the appearance of large hemopoietic stem cells around the blood vessels. The stem cells proliferated and differentiated to form hemopoietic bone marrow. This process was similar to the embryogenesis of bone and bone marrow, but the hemopoietic activity of the BMP-induced bone was transient. The bone marrow was converted to fatty tissue within 2 weeks of its appearance. This study showed that implantation of BMP in the ectopic sites offers a useful model to investigate the neogenesis of ectopic bone marrow and the regulation of its activity.

Adipose Tissue↗
PubMed1991

[Bone marrow changes at several stages of HIV infection, studied on bone marrow biopsies in 85 patients].

Bone marrow biopsies from eighty-five patients with different stages of HIV infection were reviewed. Biopsies were generally indicated to evaluate peripheral blood abnormalities, but suspicion of lymphoma and other specific pathologies was another important indication. The histopathological features are described and are often suggestive of HIV infection but non-specific. Hypercellularity (72.9%), dysmyelopoiesis (78.8%), plasma cell hyperplasia (97.7%), lymphoid infiltration (27%) and histiocytosis with or without granulomata (11.7%) were the most striking abnormalities. Other frequent features include: increased stainable iron deposits, venous stasis and serous atrophy (gelatinous transformation). Marrow hypoplasia is rather infrequent (28.2%) and usually a terminal event of AIDS. Bone marrow biopsies revealed opportunistic and neoplastic complications in seven cases, with demonstration of pathogens in four cases (Mycobacterium avium, Cryptoccocus neoformans, Toxoplasma gondii and Leishmania donovanii) and malignant lymphomas in three other cases (one Burkitt's lymphoma and two Hodgkin's disease). Bone marrow biopsy provides useful information for the diagnosis and prognosis of HIV infection and for the diagnosis of complications.

Biopsy↗
PubMed1978

Cytological analysis of bone marrow present in the bone nodules induced by human FL cells in mice.

Bone marrow cells recovered from bone nodules induced in mice by intramuscular transplantation of human FL cells were compared with the host femoral bone marrow. The precursors and mature forms of all types of blood cells were found in the induced bone marrow. The concentration of lymphocytes was significantly higher, and that of erythropoietic cells significantly lower in the induced bone marrow as compared with heterotopic femoral bone marrow.

Animals↗
PubMedDate not supplied

[Treatment of neoplastic hematologic diseases with intensive radio-chemotherapy and transplantation of cryopreserved autologous bone marrow].

Autologous bone marrow transplantation (ABMT) allows application of intensive myeloablative therapy aimed at eradication of neoplastic disease by facilitating haematopoietic reconstitution. Between March and June 1988, four patients (two with acute myelogenous leukaemia in first remission, one with acute lymphoblastic leukaemia in second remission, and one with Burkitt lymphoma, stage IV with CNS involvement in second remission) received this treatment. Methods of collecting, processing and freezing bone marrow as well as thawing and reinfusion of the marrow into patients after intensive chemoradiotherapy are described. Viability of bone marrow cells tested by the dye exclusion method after freezing and thawing process was 89, 88, 91 and 78%, respectively. CFU-GM recovery in culture, as a test of marrow stem cells clonogenicity was between 63,3 and 156,5%. Patients received between 1,7 and 3,0 x 10(8)/kg nucleated cells and 4,0 to 7,6 x 10(4)/kg CFU-GM, respectively. In all four patients stable haematopoietic reconstitution was achieved. The bone marrow function was evident mainly at 11th day after marrow reinfusion. Leukocyte count reached 1,0 x 10(0)/L in 11 to 15 days, and granulocyte count raised more than 0,5 x 10(9)/L in 19 to 37 days after transplantation. Platelet recovery was prolonged with the minimum of 29 days and maximum of more than 60 days to reach 20 x 10(9)/L. Side effects caused by the intensive radiochemotherapy were moderate. Bacterial, fungal and viral infections in early posttransplant period were successfully treated. All patients have survived and left the hospital 63, 54, 36 and 65 days after ABMT, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow Transplantation↗
PubMed1981

Early erythropoiesis in foetal rat bone marrow: evidence for a liver-to-bone marrow relay.

Erythropoietic activity of foetal rat femoral marrow was examined during the last four days of intra-uterine life. Insignificant at day 18, it develops slowly thereafter until birth. In the non-suckled neonate (not older than two hours), it appears notably enhanced. In order to test the potential of the foetal marrow to develop precocious or increased erythropoiesis, the activity of the erythropoietic organ predominant at this time, the liver, was altered by modifying the level of circulating corticosteroids, which govern its function. Maturation and involution of the hepatic erythron wee prevented by corticosteroid deprivation of the foetus (maternal adrenalectomy and foetal hypophysectomy). Precocious maturation and exhaustion of the hepatic erythron was induced by submitting foetuses to corticosteroids excess from day 14. Both corticosteroid deprivation and excess increase the erythropoietic activity of the femoral marrow. This activity can reach and even exceed by day 20 of intrauterine life that in neonatal marrow. Foetal hepatic erythron misfunction can therefore initiate and stimulate bone marrow erythropoiesis. The study of circulating red blood cells demonstrates that : (1) anaemia initiates medullary erythropoietic activity; (2) this anaemia is largely corrected by the bone marrow. The regulatory mechanism is presumably erythropoietin mediated.

Adrenalectomy↗
PubMedDate not supplied

Ultrastructural findings of bone marrow in a case with malignant osteopetrosis following successful allogeneic bone marrow transplantation.

A nine-month-old female patient suffering from malignant osteopetrosis was evaluated by light and transmission electron microscopic study before and following allogeneic bone marrow transplantation (BMT). Bone marrow specimens were obtained from iliac crest biopsies. Before BMT, the bone marrow had an irregular appearance and was filled with bridging bony trabeculae devoid of cells. Following BMT, the marrow had an almost normal appearance with no myelofibrosis and a relatively regular distribution of hematopoletic cells. The osteocytes were visible in their lacunae in the bone matrix. Presence of bone resorbing and bone forming cell together demonstrated that the bone was beginning to gain its normal dynamic structure. These findings were in accordance with the clinical, laboratory and radiological data which showed the beneficial effect of the therapy.

Bone Marrow↗
PubMed1989

Report from the International Bone Marrow Transplant Registry. Advisory Committee of the International Bone Marrow Transplant Registry.

The International Bone Marrow Transplant Registry (IBMTR) receives and analyses detailed information contributed by transplant teams at more than 175 institutions worldwide. This collaborative research effort has grown rapidly; there are now more than 8000 cases in the database. This is a summary of the current status of bone marrow transplantation in leukemia and severe aplastic anemia, a brief summary of key findings reported by the IBMTR during the past year, as well as studies planned for the coming year.

Anemia, Aplastic↗
PubMed1991

CD34 expression by stromal precursors in normal human adult bone marrow.

Normal bone marrow cells were isolated by fluorescence-activated cell sorting (FACS) on the basis of CD34 antigen expression and then assayed in vitro for colonies of fibroblastic cells (fibroblast colony-forming units [CFU-F]). Greater than 95% of detectable CFU-F were recovered in the CD34+ population, while their numbers were markedly depleted in the CD34- population. Additional experiments showed that the majority of CFU-F exhibited high forward and perpendicular light scatter and low-density CD34 antigen. Growth of sorted cells in medium optimized for long-term marrow culture (LTMC) produced a complex mixture of adherent stromal elements including fibroblasts, adipocytes, smooth muscle cells, and macrophages. Monoclonal antibody STRO-1, which identifies bone marrow stromal cells, reacted with approximately 5% of CD34+ cells, which included all CFU-F and stromal precursors in LTMC. Experiments using soybean agglutinin (SBA) further showed that these stromal elements were restricted to a population of bone marrow cells with the phenotype CD34+/SBA+. These properties of stromal precursors are quite distinct from those of primitive hematopoietic progenitors, showing that although the precursors of the hematopoietic and stromal systems share expression of CD34, they are otherwise phenotypically distinct cell types.

Antibodies, Monoclonal↗