Changes in bone marrow hemopoiesis in donor rabbits

Summary It was shown in an experiment on 17 rabbits that animals from which bone marrow had been extracted in amounts of 10–20 ml one time, 2–3 times at intervals of 4–5 months or 7–8 times at intervals of 1–1.5 months were in good condition during the entire experiment and even put on weight. Four animals from which bone marrow was taken in large quantities (25–50 ml 3–4 times at 4–5 months intervals) developed anemia of a hyporegenerative character 12–16 months after the beginning of the experiment, which was followed by a septic conditions with multiple abscesses in the visceral organs. Hence, repeated extractions of large quantities of bone marrow may bring about severe disorders in hemopoietic processes and a reduction in the body resistance.(Presented by Active Member AMN SSSR A. F. Tur) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 60, No. 8, pp. 43–46, August, 1965     

Changes in the peripheral blood and bone marrow of rabbits in experimental epilepsy

Summary The effect of experimentally induced cardiazol epilepsy on the peripheral blood and bone marrow was studied in 16 rabbits. The epileptiform attacks provoked leukocytosis and a rise of the red cell count. The leukocytic reaction appeared during the first few minutes of an increased number of lymphocytes, and later on of pseudoeosinophils. Following several attacks, an intensified granulopoiesis and an increased number of platelet producing forms of megakaryocytes were observed in the bone marrow.There were no modifications in the red blood picture.The author concludes that the changes occuring in the blood are connected with the intensified bone marrow function, under the effect of epilepitform fits.(Presented by Active Member AMN SSSR V. V. Parin) Translated from Byulleten' éksperimental'noi biologii i meditsiny Vol. 49, No. 2, pp. 61–64, February, 1960.     

Antropyloric G-cell hyperplasia in hypercalcemic rabbits bearing the VX2 carcinoma.

The number of distribution and the numbers of G cells in the antropyloric region of the rabbit stomach were mapped employing immunoperoxidase localization and morphometric quantitation and compared to similar analyses in hypercalcemic rabbits bearing the VX2 carcinoma. In normal animals, G cells were confined to the lower third of the antropyloric mucosa, where they were randomyly distributed within the mucosal glands. In contrast, tumor-bearing animals showed an extension of these cells into the middle third of the antropyloric mucosa. The absolute counts of G cells in control rabbits were 5.3 +/- 0.78 (mean +/- SE) per unit area, while those in hypercalcemic tumor-bearing rabbits were 11.9 +/- 0.46, a statistically significant increase. It is concluded that rabbits bearing VX2 carcinoma have G-cell hyperplasia.     

A local renin-angiotensin system in the bone marrow

The renin-angiotensin system has been considered to be a circulating system that controls blood pressure and electrolyte homeostasis. It is now clear, however, that the renin-angiotensin system must also be regarded as a local tissue system within many organs. Renin-angiotensin system peptides are capable of producing the hyperplasia and growth of cells. The haematopoietic bone-marrow system is characterized by turnover, proliferation and differentiation of cells. We propose that there exists a locally active renin-angiotensin system that is intrinsic to bone marrow and that might affect the growth of haematopoietic colonies, and the production, proliferation and differentiation of cells. The local synthesis of a particular protein can be deduced from the presence of the corresponding messenger ribonucleic acid. To prove our hypothesis, we propose that attempts be made to quantitatively analyse messenger ribonucleic acids for components of the renin-angiotensin system in tissues from bone marrow biopsies. Demonstration of an endogenous renin-angiotension system in bone marrow might lead us to a better understanding of the production of haematopoietic cells and of the excessive cell-growth associated with neoplastic diseases of the blood.     

Biological time and the effects of hydroxyurea on DNA synthetic activity of bone marrow and tumor cells in mice bearing the Ehrlich ascites carcinoma

The objective of this experiment was to attempt to induce, with hydroxyurea (HU), significant quantitative differences in the level of DNA-synthetic activity (DNA-SA) between a neoplastic cell population (the Ehrlich ascites carcinoma or EAC) and bone marrow in the same animal. Mice bearing a 5-day-old EAC were standardized to and kept on an LD 12:12 cycle (light 0600–1800 hr). They were treated with 500 mg/kg HU at 0500 hr (23 hr after lights on, or HALO) or at 1700 hr (11 HALO). DNA-SA was determined by liquid scintillation counting of ³H-thymidine incorporation into chemically isolated DNA. DNA-SA in bone marrow and EAC cells was monitored over the next 60 hr with subgroups of ten mice each killed every 3 hr beginning 3 hr after treatment with HU. The circadian system of the host influenced the response of the bone marrow to HU; i.e., the response to HU administered at 0500 hr was different both qualitatively and quantitatively from that for HU given at 1700 hr. Comparisons of DNA-SA in bone marrow and EAC from the same animal revealed time points after treatment with HU when DNA-SA in the EAC was high, but DNA-SA in bone marrow was low. These differences in the level of DNA-SA between a tumor cell population and bone marrow should be of therapeutic value; i.e., executor doses of anti-DNA-SA drugs such as cytosine arabinoside could be given at that point in time after treatment with HU when DNA-SA in the tumor was high, but DNA-SA in the bone marrow was low.     

激素对兔骨髓间充质干细胞神经递质表达的影响

背景：激素性股骨头坏死的确切发病机制仍未清楚,研究发现神经系统可通过多种途径调控骨髓间充质干细胞的分化,激素可能通过影响其调控机制而引起骨坏死。 目的：观察在激素作用下,骨髓间充质干细胞中神经递质或其受体mRNA表达的变化。 方法：密度梯度离心和贴壁培养获得兔骨髓间充质干细胞。将传代培养的第3代细胞随机分为两组,实验组加入浓度为10-7 mol/L的地塞米松,对照组正常培养。分别于诱导后第4,7,11,15天,测定细胞中神经生长因子、成纤维细胞生长因子、降钙素相关基因肽受体、血管活性肠肽受体、P物质受体及过氧化物酶体增殖子活化受体γ的mRNA表达。 结果与结论：实验组神经生长因子、成纤维细胞生长因子、降钙素相关基因肽受体、血管活性肠肽受体和P物质受体的mRNA表达较对照组明显降低,而过氧化物酶体增殖子活化受体γ mRNA表达较对照组明显增高,差异均具有显著性意义(P < 0.01),实验组各因子在不同时间点间进行比较却无明显差异(P > 0.05)。结果表明大剂量激素可使骨髓间充质干细胞中具有成骨或成血管作用的神经递质或其受体表达下降,这可能与激素性股骨头坏死发生的机制有关。     

Changes in plasma beta 2 microglobulin concentrations after allogeneic bone marrow transplantation.

Plasma concentrations of beta 2 microglobulin (B2M), the light chain of the class I major histocompatibility complex, were measured serially in 26 patients undergoing allogeneic bone marrow transplantation (BMT). The concentrations fell after conditioning treatment, and recovered when the marrow was transplanted. Bacterial infection did not influence B2M concentration, but nine of 22 episodes of acute graft versus host disease were associated with raised concentrations. Increased plasma B2M concentrations were also a feature of eight episodes of chronic graft versus host disease, and these fell after treatment. Reactivation of herpes simplex, varicella zoster, or cytomegalovirus infections were also accompanied by raised B2M concentrations. Three patients with cytomegalovirus pneumonitis had high concentrations of plasma B2M, the rise starting between five and 22 days before onset of symptoms. Although it is non-specific, serial measurement of plasma B2M in patients undergoing BMT may be clinically useful in monitoring chronic graft versus host disease.     

The role of the bone marrow in bovine trypanotolerance I. Changes in blood and bone marrow inTrypanosoma congolense-infected cattle

This study compared the changes in the bone marrow (BM) of five trypanotolerant N'Dama cattle with those of four trypanosusceptible Boran cattle during trypanosome infection. In the early parasitaemic phase, from 12 to 21 days postinfection (DPI), tsetsetransmitted primaryTrypanosoma congolense IL 1180 infection induced parasitaemia, slight depression in packed cell volume (PCV), marked leucopenia due to lymphocytopenia and eosinopenia, and thrombocytopenia which were of similar intensity in Boran and N'Dama cattle. However, from 28 DPI until the end of the experiment on 112 DPI, the parasitaemia was higher in the Boran than in the N'Dama. Severe anaemia and leucopenia characterised by lymphopenia, neutropenia, eosinopenia and monocytopenia persisted in Boran cattle. In contrast, the PCV values dropped gradually in N'Dama cattle and from 77 DPI recovered slowly to values just below preinfection levels by 112 DPI. The total and differential leucocyte counts of the N'Dama cattle stabilised at approximately two-thirds of preinfection values between 28 and 112 DPI, and were double those of the Boran. Marked thrombocytopenia occurred in both breeds. The anaemia was initially macrocytic hypochromic but terminally became microcytic hypochromic in both breeds. Light and electron microscopic studies of sequential biopsies of the BM of these animals showed that the BM response was the key to these differences between the N'Dama and Boran. The biopsies of the BM of the N'Dama cattle were hypercellular (scored 4.5±1.0 compared to 4.0 for controls) with mild hyperplasia of erythroid cells and mild hypoplasia of myeloid cells from 28 to 112 DPI, endowing the animals with higher haemopoietic potential that enabled them to replace most lost cells. In contrast, the Boran cattle had hypocellular (scored 2.4±1.1) BM biopsies with relative erythroid hyperplasia and myeloid hypoplasia, resulting in low capacity of cell replacement manifested as severe unremitting anaemia and leucopenia. The BM of both breeds showed moderate hyperplasia of cells of the mononuclear phagocyte system. Therefore, this study showed, for the first time, that BM response is a key determinant factor of trypanotolerance as it determines the animal's capability for blood cell regeneration.     

Changes in plasma fibronectin during allogeneic bone marrow transplantation.

Plasma fibronectin concentrations were measured serially in nine patients undergoing allogeneic bone marrow transplantation. Concentrations were reduced by conditioning treatment and episodes of bacterial infection. Acute graft versus host disease may exacerbate or prolong this process. Reduced plasma fibronectin concentrations impair the function of the mononuclear phagocyte system and the maintenance of capillary endothelial integrity and may thus contribute to the morbidity and mortality in patients undergoing bone marrow transplantation.     

Changes in rectal leucocytes after allogeneic bone marrow transplantation.

Using immunohistological techniques the number of leucocytes present in the epithelium and lamina propria of the rectal mucosa were assessed in 16 allogeneic bone marrow transplant recipients, with and without evidence of graft-versus-host disease (GVHD), and compared with a non-transplant group of patients. Samples were obtained between 15 and 198 days after transplant. In marrow recipients without GVHD, compared with non-transplant cases, there was a decrease in T lymphocytes in the lamina propria due to a reduction in the helper-inducer (T4+) subset with no change in suppressor-cytotoxic (T8+) cells or epithelial leucocytes. In GVHD, the number of T lymphocytes increased both in the lamina propria and epithelium due to an increase in T8+ cells with no change in T4+ cells. Lymphocytes did not express the activation markers detected by Tac, OKT10 or HLA-DR. Macrophages and natural killer cells were not changed after transplant or in GVHD. Epithelial HLA-DR expression was detected in seven out of eight in the GVHD group, three out of eight in the non-GVHD transplant group and two out of eight in the non-transplant cases. These findings show several differences from those we have observed in cutaneous and hepatic GVHD. Although elevated numbers of T8+ cells are common to GVHD in all three sites, the precise role of these cells in producing epithelial damage is not clear.     

The role of the bone marrow in bovine trypanotolerance I. Changes in blood and bone marrow inTrypanosoma congolense-infected cattle

This study compared the changes in the bone marrow (BM) of five trypanotolerant N'Dama cattle with those of four trypanosusceptible Boran cattle during trypanosome infection. In the early parasitaemic phase, from 12 to 21 days postinfection (DPI), tsetsetransmitted primaryTrypanosoma congolense IL 1180 infection induced parasitaemia, slight depression in packed cell volume (PCV), marked leucopenia due to lymphocytopenia and eosinopenia, and thrombocytopenia which were of similar intensity in Boran and N'Dama cattle. However, from 28 DPI until the end of the experiment on 112 DPI, the parasitaemia was higher in the Boran than in the N'Dama. Severe anaemia and leucopenia characterised by lymphopenia, neutropenia, eosinopenia and monocytopenia persisted in Boran cattle. In contrast, the PCV values dropped gradually in N'Dama cattle and from 77 DPI recovered slowly to values just below preinfection levels by 112 DPI. The total and differential leucocyte counts of the N'Dama cattle stabilised at approximately two-thirds of preinfection values between 28 and 112 DPI, and were double those of the Boran. Marked thrombocytopenia occurred in both breeds. The anaemia was initially macrocytic hypochromic but terminally became microcytic hypochromic in both breeds. Light and electron microscopic studies of sequential biopsies of the BM of these animals showed that the BM response was the key to these differences between the N'Dama and Boran. The biopsies of the BM of the N'Dama cattle were hypercellular (scored 4.5±1.0 compared to 4.0 for controls) with mild hyperplasia of erythroid cells and mild hypoplasia of myeloid cells from 28 to 112 DPI, endowing the animals with higher haemopoietic potential that enabled them to replace most lost cells. In contrast, the Boran cattle had hypocellular (scored 2.4±1.1) BM biopsies with relative erythroid hyperplasia and myeloid hypoplasia, resulting in low capacity of cell replacement manifested as severe unremitting anaemia and leucopenia. The BM of both breeds showed moderate hyperplasia of cells of the mononuclear phagocyte system. Therefore, this study showed, for the first time, that BM response is a key determinant factor of trypanotolerance as it determines the animal's capability for blood cell regeneration.     

A comparison of the effects of plasma exchange and immunoadsorption on anti-insulin antibody synthesis in rabbits.

Plasma exchange (PE) and ex vivo immunoadsorption (IA) may be applicable to the removal of anti-insulin antibodies (AI-Ab) from diabetic patients. However, the removal of antibodies may prompt an increase in their rate of synthesis and an overshoot of antibody levels which may be deleterious to the patient. The effects of both PE and IA on AI-Ab synthesis were studied in a rabbit model. Rabbits were immunized with insulin and the resulting AI-Abs removed by both plasma exchange and specific immunoadsorption. Following AI-Ab removal by PE no increase in AI-Ab synthesis or antibody overshoot occurred. However a large increase in AI-Ab synthesis and overshoot occurred following specific AI-Ab removal by immunoadsorption. Despite similar reductions in AI-Ab levels by PE and IA, no increase in antibody synthesis occurred due solely to antibody removal. It is likely that antigen released from the immunoadsorbent stimulated the increase in antibody synthesis following immunoadsorption. These findings are relevant to the clinical application of both PE and IA.     

A comparison of flow cytometry,bone marrow biopsy,and bone marrow aspirates in the detection of lymphoid infiltration in B cell disorders

AIMS: To evaluate the diagnostic value of bone marrow aspirates, trephine biopsies (BMB), and flow cytometry (FC) in the assessment of bone marrow infiltration in chronic lymphoid disorders. METHODS: Investigations were carried out in 110 diagnostic and follow up specimens from B cell disorders, namely: chronic lymphocytic leukaemia (CLL; 65), non-Hodgkin's lymphoma (NHL; 39), and hairy cell leukaemia (HCL; 6). A selected panel of monoclonal antibodies was used both for FC and immunohistochemistry. RESULTS: In CLL there was agreement between the three investigations in 71% of samples and in 88% when only FC and BMB were compared. In nine of 65 samples, FC and BMB were positive, although the aspirate was reported as negative. Four BMB negative samples had minimal residual disease (MRD) detected by FC, whereas two samples were positive both on BMB and aspirate but showed no evidence of disease on FC. In NHL, there was agreement between the three investigations in 22 of 39 cases, and in 27 of 39 cases there was agreement between FC and BMB. In eight of 39 NHL cases, FC was negative but the BMB was either positive (five) or uncertain (three), whereas in three of 39, FC was positive but BMB was either negative (one) or uncertain (two). In three of five uncertain BMB, no clonal population was detected by the polymerase chain reaction, whereas in the remaining two cases the nodular aggregates disappeared on further sectioning. CONCLUSIONS: Both BMB and FC are better than bone marrow aspirates for the detection of infiltration in B cell disorders. FC might be slightly more sensitive than BMB to detect MRD in CLL, whereas BMB may be slightly better than FC in NHL.