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Reactivity of the workshop monoclonal antibodies with ovine bone marrow cells and bone marrow-derived monocyte/macrophage and mast cell lines.

The workshop monoclonal antibodies were tested by flow cytometry for reactivity against: (1) ovine bone marrow cells, (2) cultured bone marrow-derived monocyte/macrophage cell lines and (3) cultured bone marrow-derived mast cell lines. Both single and two-colour immunofluorescence tests were performed. The results of these analyses are presented and discussed.

Animals↗

[Experimental study and clinical application on osteogenesis of percutaneous autogenous bone marrow grafting in bone defects].

OBJECTIVE: To observe the osteogenesis of percutaneous autogenous bone marrow grafting in cicatricial bone defect, to seek a good method for treating fracture nonunion. METHODS: Eighteen rabbits were adopted in this study. 1 cm bone defect model was made in each side of radius, 6 weeks later, 2 ml autogenous bone marrow was injected in the right radial bone defect as experimental group, 2 ml autogenous peripheral blood in the left side as control group. X-ray features, histologic changes, Ca and P content in the site of bone defect were studied in various times. Also 15 patients were treated clinically for the nonunion fracture, the average time from nonunion to bone marrow grafting was 13 months. RESULTS: In experimental group, the increasing new bone tissue were observed in X-ray and histologic examination. While in control group, no osteogenesis was observed. Ca and P content of experimental group was higher than that of control group. For the 15 patients, 13 cases healed in 5-9 months, 2 cases failed. CONCLUSION: Percutaneous autogenous bone marrow grafting is capable of osteogenesis in the cicatricial bone defects. It can be used in nonunion cases which are not fit for operation of bone grafting because of poor condition of the skin.

Adolescent↗

Regeneration of CALLA (CD10+), TdT+ and double-positive cells in the bone marrow and blood after autologous bone marrow transplantation.

In this prospective study we investigated the frequency of CD10+, TdT+ and CD10+TdT+ mononuclear cells in the bone marrow (BM) and peripheral blood (PB) before and after autologous bone marrow transplantation (ABMT). 49 patients treated for acute lymphoblastic or myeloblastic leukaemia, malignant lymphoma or multiple myeloma were included. A significant increase in CD10+ cells occurred in BM in both children and adults after ABMT. In children, we also found a significant increase in CD10+ cells in PB. In individual patients remaining in remission, up to 34% CD10+ cells having a normal Ig kappa/lambda light chain ratio were recorded after ABMT. In children, the percentage of TdT+ and CD10+ TdT+ cells increased significantly in BM. In most cases the CD10/TdT-ratio was greater than 1.0, but during early regeneration after ABMT this ratio was less than 1.0 in several patients remaining in complete remission. In patients remaining in remission, CD10+TdT+ cells were detected in the blood in only 2 out of 140 samples tested, and the proportion of these cells never exceeded 0.03%. We conclude that quantitation of CD10+TdT+ cells in peripheral blood is helpful in the evaluation of complete remission in patients treated for pre-B-ALL.

Adult↗

The entry of the prothymocyte into the thymus after lethal irradiation and bone marrow transplantation. I. Seeding of bone marrow cells into the thymus.

Bone marrow (BM) cells arrive in the thymus of lethally irradiated mice as early as three hours after bone marrow transplantation (BMT). They can be recognized by labeling of the injected cells with Hoechst 33342 (direct homing assay). In order to relate the immigrated BM cells to thymocyte precursor cells, direct homing and thymus repopulation experiments were compared. It was shown that homing of BM cells depends on the time between lethal irradiation and BMT, while it was previously shown that thymus repopulation does not. In addition, thymic immigrants were smaller than precursor cells committed to the T cell limeage (prothymocytes) and their progenitors. A cell population obtained from normal BM cells and enriched in stem cells (purified stem cells) was previously shown to repopulate the thymus similarly as BM cells from mice pretreated in vivo with 5-fluorouracil (FUBM). Both cell suspension showed a delayed thymus repopulation when compared to normal BM. This is indicative for a depletion of prothymocytes in these cell suspensions. In the direct homing assay, however, it was found that relatively many cells from FUBM seeded into the thymus, while purified stem cells did not. These results indicate that most if not all donor cells that are present in the thymus at three hours after BMT are not thymocyte precursor cells.

Animals↗

Heterotopically induced bone marrow. I. Cellular composition of bone marrow derived from the heterotopic ossicles induced in mice by xenogeneic epithelia of human amnion and dog's transitional epithelium.

Following heterotopic osteogenesis by implantation of xenogeneic epithelia (FL and WISH cell line, transitional epithelium of dog) in mice a biogenesis of hemopoietic tissue among induced ossicles is observed. Precursors and mature forms of all types of blood cells are found in the induced bone marrow. The concentration of lymphocytes in the induced bone marrow is higher, and that of erythropoietic cells lower as compared with orthotopic femur bone marrow. The yield of myeloid cells varied from 0.14 to 3.61 x 10(6) cells per induced bone-containing nodule.

Amnion↗

Assessment of bone marrow blood flow using positron emission tomography: no relationship with bone marrow cellularity.

Bone marrow blood flow has been assessed using positron emission tomography and the 15O-labelled carbon dioxide steady-state technique. The measurements were performed at the site of the posterior iliac crest. The bone marrow blood flow was 10.0 ml/min/100 cm3 +/- 3.0 (SD) in normal volunteers. It was markedly increased in patients with polycythaemia vera (26.9 +/- 4.6), chronic granulocytic leukaemia (25.2 +/- 3.9) and myelofibrosis (35.1 +/- 7.3). However, bone marrow blood flow did not differ from normal in patients with aplastic anaemia, chronic haemolysis or chronic lymphocytic leukaemia. There was no relationship between bone marrow cellularity and bone marrow blood flow. The data show that bone marrow blood flow is markedly elevated in polycythaemia vera, myelofibrosis and chronic granulocytic leukaemia and suggest that bone marrow cellularity is not a major factor in regulating bone marrow blood flow.

Bone Marrow↗

[Advances of bone marrow biopsy pathology in diagnosing lymphoma bone marrow involvement].

The diagnosis of lymphoma bone marrow involvement (LBMI) is mainly based on bone marrow biopsy. Pathology of LBMI in Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL) are different. The morphology, distribution patterns and immunophenotype of most tumor cells in bone marrow are consistent with those in extramedullary sites, but few may show some discrepancy. This article compared the pathologic features of LBMI in HL, B-NHL and T-NHL, and reviewed advances of bone marrow biopsy pathology in diagnosing LBMI from the aspects of morphology, immunohistochemistry, and lymphoma gene rearrangement.

Biopsy↗

[Detection of residual cells contaminating the bone marrow in neuroblastoma. Apropos of 80 bone marrow evaluations].

Eighty bone marrow studies (each including 4 aspirates and 4 trephine biopsies) were performed in 37 children with stage IV neuroblastoma to assess the most accurate means for detection of invasion by neuroblastoma cells. Among 38 abnormal results, only trephine biopsy(ies) were found positive in 24 cases (63%), only aspirate(s) in 5 cases (13%), and both in 9 cases (24%). In 37% of abnormal results, only 1 of the 8 tests performed was found positive. No benefit was obtained from either associated touch imprints of iliac biopsies (67 investigations), or exploration of extra-iliac sites (66 sternums, 53 tibias). Two monoclonal antibodies, claimed to be specific for detection of neuroblastoma cells in bone marrow, were used in 56 investigations; they could detect minimal residual disease in some cases, but they were unreliable when no staining was obtained if initial phenotype of neuroblastoma had not been assessed, or when few isolated cells were observed. Prospective studies using immunocytology and immunohistology are thus warranted.

Antibodies, Monoclonal↗

Primary treatment of acquired aplastic anemia: outcomes with bone marrow transplantation and immunosuppressive therapy. Seattle Bone Marrow Transplant Team.

BACKGROUND: Both immunosuppressive therapy and bone marrow transplantation are accepted treatments for patients with aplastic anemia. Choosing one of these therapies for a given patient depends not only on donor availability but also on such factors as patient age. OBJECTIVE: To compare survival rates and long-term complications after bone marrow transplantation or immunosuppressive therapy in patients with acquired aplastic anemia and to identify prognostic factors associated with improved survival. DESIGN: Center-based, retrospective analysis. SETTING: Referral center for patients with aplastic anemia. PATIENTS: 395 patients with acquired aplastic anemia. INTERVENTION: Bone marrow transplant from an HLA-identical, related donor or immunosuppressive therapy. MEASUREMENTS: Kaplan-Meier survival curves, results of log rank tests, and cumulative incidence curves. RESULTS: Of 168 bone marrow transplant recipients, 89% had sustained engraftment. Forty-six patients developed grade II to IV acute graft-versus-host disease, and 68 developed chronic graft-versus-host disease that required therapy. Of 227 patients who received immunosuppressive therapy, 44% achieved a complete, partial, or minimal response. Fifty-four percent died or had no response to therapy. Actuarial survival at 15 years was 69% for bone marrow transplant recipients and 38% for patients receiving immunosuppressive therapy (P < 0.001). Improved survival was associated with having bone marrow transplantation as primary therapy, being younger, having no transfusion before transplantation, and having a higher absolute neutrophil count. Disease duration, year of therapy, sex, refractoriness to platelet transfusions, and previous treatment with androgens or corticosteroids did not significantly affect survival. CONCLUSIONS: Data from this center suggest that bone marrow transplantation may be preferred for younger patients with acquired aplastic anemia who have matched, related donors. Long-term survival is excellent for patients who respond to either form of therapy.

Actuarial Analysis↗

Effects of experimental joint inflammation on bone marrow and periarticular bone. A study of two types of arthritis, using variable degrees of inflammation.

The effects of joint inflammation on bone marrow and periarticular bone were studied in mice using antigen-induced arthritis and zymosan-induced arthritis as models for an immune and a non-immune-mediated chronic inflammation. To allow for a comparison of the two types of arthritis care was taken to induce comparable degrees of inflammation as evaluated with 99mTechnetium uptake and histology. The antigen-induced arthritis caused a significant suppression of the mitotic activity in the bone marrow close to the inflammatory focus during the first days of arthritis. The zymosan-induced arthritis did not produce alterations of the bone marrow activity. Both types of arthritis were able to induce long-lasting and irreversible damage to cartilaginous and bony structures. Apposition of bone was observed in both types of arthritis although much earlier in the antigen-induced arthritis. The apposition of bone was found to emerge largely from the periosteum and not from the epiphyseal plates, as shown by 125I-deoxyuridine autoradiography. Qualitative and quantitative differences suggest that joint inflammation which is immunologically mediated, results in more severe (peri)articular tissue damage than a non-immunological arthritis.

Animals↗

Bone blood flow and in vitro proliferation of bone marrow and trabecular bone osteoblast-like cells in ovariectomized rats.

Ovariectomy in the rat induces a rapid osteopenia associated with an elevated bone turnover. One hundred and twenty-day-old rats were ovariectomized (OVX) or sham-operated (n = 6-8 per group and per time period studied). 45Ca accretion rate and bone blood flow (microspheres trapping technique) in the femurs were determined at 28, 42, 84, and 119 days after ovariectomy. Both parameters were markedly increased by 84 days and subsided thereafter. At the 42nd day, when bone turnover was maximal, bone marrow and trabecular bone cultures were obtained from sham-operated and ovariectomized animals (n = 10/group). Proliferation rate of bone marrow cells and trabecular osteoblast-like cells estimated by fibroblast colony-forming units (FCFU) efficiency and cell counting was markedly increased in primary and secondary cultures in ovariectomy. These data fitted well with the enhanced number of osteoblasts observed in situ in the long bone metaphyses of estrogen-depleted animals. As estrogens were shown in the literature to inhibit proliferation of the red cell line and of other hemopoietic lines, it is possible that estrogens, through a general mechanism, inhibit hemopoietic and stromal lines and also the proliferation of bone marrow-derived trabecular bone cells.

Animals↗

Changes in erythropoietin pharmacokinetics following busulfan-induced bone marrow ablation in sheep: evidence for bone marrow as a major erythropoietin elimination pathway.

The contribution of the bone marrow to in vivo erythropoietin (EPO) elimination was evaluated by determining EPO pharmacokinetic (PK) parameters in five adult sheep in a paired manner before and after chemotherapy-induced marrow ablation. After busulfan-induced bone marrow ablation, EPO PK demonstrated progressive decreases in plasma clearance (CL), elimination half-life [t1/2(beta)], and volume of distribution at steady state (Vss) with concomitant increases in mean residence time (MRT). Eight days after beginning busulfan treatment, there were no further changes in CL, t1/2(beta), MRT, and Vss. Only 20% of baseline CL remained by day 8. The volume of distribution (Vc) and distribution half-life [t1/2(alpha)], in contrast, remained unchanged from baseline. White blood cell counts and reticulocytes gradually declined after the start of marrow ablation. Examination of bone marrow core biopsy samples obtained on day 10 revealed less than 10% of baseline marrow cellularity. No colony-forming unit erythroid (CFU-E) colonies were found after 6 days of incubation for bone marrow aspirates drawn at days 8 and 13 following busulfan treatment, whereas pre-busulfan aspirates yielded 29 CFU-E colonies per 10(5) cells in CFU-E cultures. Treatment of a sheep with 5-fluorouracil showed changes in PK parameters that were similar to the results from treatment with busulfan. The present study indicates that the bone marrow significantly contributes to the elimination of EPO in vivo.

Animals↗

Percentage of S-phase cells in bone marrow aspirates, biopsy specimens and bone marrow aspirates corrected for blood dilution from patients with acute leukemia.

For 14 patients with acute leukemia flow cytometry was used to determine the percentage of cells in S-phase flushed out of a bone marrow biopsy compared with the percentage in a bone marrow aspirate; there was a statistically significant difference (p less than 0.01) between the two. The percentage dilution of the bone marrow aspirate by peripheral blood was then calculated, according to Holdrinet et al. [1], in order to correct the percentage S-phase cells in the aspirate. The data presented show that when the percentage S-phase cells in the aspirate is corrected for blood dilution, it closely approaches the percentage S-phase cells in the biopsy (p greater than 0.10).

Biopsy↗

Recombinant human erythropoietin (rhEPO) administration to marrow donors. Bone Marrow Transplantation (BMT) Team.

Reviewing 37 adult marrow donors, the hemoglobin (Hb) level at 3 weeks before marrow aspiration was predictive for the low Hb level just before the operation. Accordingly, erythropoietin was given to donors whose Hb level was less than 130 milligrams at 3 weeks before operation. One hundred units/kg of recombinant human erythropoietin (rhEPO) was given subcutaneously 3 times a week for 3 weeks. Four donors received rhEPO, and their data were compared with those from four historical controls. The initial average Hb level was 126.3 milligrams in the rhEPO group and 125.3 milligrams in the control group. The preoperative Hb level was 133.0 milligrams in the rhEPO group and 104.0 milligrams in the control group; the postoperative Hb levels were 123.8 and 90.8 milligrams, respectively. Engraftment was obtained in all patients who received the marrow from the donors treated with rhEPO and there was no significant delay in the recovery of white blood cell, reticulocytes and platelet counts. A 3-week regimen of erythropoietin may help prevent the donor's need to receive allogeneic blood transfusion, when the initial Hb levels were below 130 milligrams.

Adolescent↗