Population balance model of in vivo neutrophil formation following bone marrow rescue therapy

In this paper, we develop a simple four parameter population balance model of in vivo neutrophil formation following bone marrow rescue therapy. The model is used to predict the number and type of neutrophil progenitors required to abrogate the period of severe neutropenia that normally follows a bone marrow transplant. The estimated total number of 5 billion neutrophil progenitors is consistent with the value extrapolated from a human trial. The model provides a basis for designing ex vivo expansion protocols. This revised version was published online in August 2006 with corrections to the Cover Date.     

Biochemical genetic comparison of the Chinese and European races of the common carp

An electrophoretic survey of the common carp revealed 33 loci. Nine were found to be polymorphic including two phosphoglucose isomerase loci, a phosphoglucomutase locus, three esterase loci, a lactate dehydrogenase locus, a malate dehydrogenase locus, and transferrin. Five of these polymorphic loci are reported for the first time, the two phosphoglucose isomerase loci, a phosphoglucomutase locus and two of the three esterase loci. Differences in allele frequencies between the European and Chinese races were found at most loci.     

Modulation of one of three murine bone marrow stromal cell lines to adipose cells by serum and insulin

Adipose cells have been recognized as an integral component of the bone marrow hematopoietic microenvironment in vivo and as an essential cell type required for in vitro maintenance of stem cells. Four stromal cell lines obtained from the adherent cell population of murine bone marrow cultures have been enriched and purified by multiple trypsinizations. We noted that these cell lines exhibited an accumulation of vacuoles of lipid, the extent of which varied be-tween cell lines in response to a change from medium containing 10% fetal calf serum to medium containing 20% horse serum. The lipid was lost when the cell lines were transferred back into the medium supplemented with fetal calf serum. In light of the reported lipogenic and antilipolytic effects of insulin on fibroblasts and adipocytes, we investigated the ability of insulin to induce adipocyte transformation of these bone marrow stromal cell populations. Three cell lines were exposed to bovine insulin at concentrations ranging from 10^?9 to 10^?6 M. All three cell lines responded to the insulin by accumulating lipid, but the extent of accumulation and the insulin concentration at which maximum lipid content was attained were population specific. One cell line (MC₁) responded fully at physiological levels of insulin (10^?9 M), whereas the other two showed lipid accumulation only at pharmacological concentrations. The initial growth of MC₁ was inhibited in the presence of 10^?9 M insulin which is compatible with the observed differentiation to adipocytes. The growth of MC₃ was unaltered in the presence of physiological concentrations of insulin, whereas that of MC₄ was accelerated. Grafts of organ cultures of the cell lines under the kidney capsule of syngeneic mice developed specific characteristics rep-resentative of the different cell lines. In particular, the majority of the grafts of MC₁ consisted primarily of fat cells which were not observed in the grafts of MC₃ and MC₄. These data strongly suggest that these cell lines comprise cells with different potentialities and that the MC₁ line represents a preadipocyte stromal cell of bone marrow.     

PGE2 induces the transition from non-adherent to adherent bone marrow mesenchymal precursor cells via a cAMP/EP2-mediated mechanism

When mesenchymal precursor cells from bone marrow are cultured in the presence of dexamethasone, the existence of distinct non-adherent and adherent populations can be demonstrated. The addition of PGE₂, forskolin, or dibutyryl-cAMP can induce a transition from the former to the latter and this may be an important mechanism in the bone anabolic effects of PGE₂. On the other hand, phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, and sulprostone, an agonist for the PGE₂ receptor EP₁/EP₃ subtypes, had no effect. The phosphodiesterase inhibitor, isobutylmethylxanthine (IBMX), had a synergistic effect in combination with PGE₂, whereas neomycin, an inhibitor of inositol phosphate activity, had no effect, and LiCl, an inhibitor of inositol triphosphate metabolism, had an inhibitory effect on the PGE₂-induced transition. Consistent with this, the addition of PGE₂ to non-adherent bone marrow cells caused a 100% increase in cAMP synthesis. These results suggest that the induction of the transition from non-adherent to adherent osteoblast precursor is mediated by the EP₂-PGE₂ receptor subtype via an increase in intracellular cAMP synthesis.     

孕期应激对子代大鼠骨髓淋巴干细胞发育的影响

孕期应激对子代产生的影响是多方面的,这种影响是复杂的。研究表明,出生前的应激经历可导致出生后子代长期的免疫功能改变。这些改变追其根源与骨髓淋巴干细胞的改变有关。本文综述了大鼠孕期经历应激的子代骨髓淋巴干细胞所受的影响及免疫系统的相关改变,并根据现有的研究提出假说,为进一步研究孕期应激导致子代免疫系统改变的机理研究提供新的思路。     

Recent advances in bone marrow biopsy pathology

The second quarter of 2009 saw steady advances in bone marrow biopsy (BMB) pathology. The following publications are a personal selection of the highlights. Quality issues in diagnostic immunohistochemistry for BMB have largely been ignored in external quality assurance programmes, and this issue is highlighted. In other areas, publications reflecting advances in flow cytometry and aspirate morphology are discussed where translation to the BMB is possible. Classifications undergo constant change, and several publications address the redefinition of the cut off points between malignancy, benign, and normal. Lastly, current scientific research is presented where it is relevant to the understanding of BMB pathobiology.     

人骨髓基质细胞体外分离及定向培养内皮细胞

用Ficoll(比重1.077 g/ml)从正常成人骨髓中分离骨髓基质细胞(BMSCs),DMEM-HG 培养基内含20?S、GM-CSF(100 u/ml)、VEGF(10 ng/ml)、FGF(5 ng/ml)、L-谷氨酰胺(2mmol/ L)、肝素(90 u/ml),以及抗生素液进行定向培养和扩增其中的内皮细胞(ECs),Ⅷ因子相关抗原的免疫组化法和透射电镜观察(TEM)鉴定其细胞的性质。结果5.0×105个BMSCs在体外经定向ECs 培养和扩增8代后,获得了6.0×109个ECs,扩增了约1.2×104倍。70%-80%的细胞对Ⅷ因子相关抗原免疫组化呈阳性反应;光镜下细胞呈典型的“鹅卵石”样;TEM下可观察到胞浆内有Weible- palade小体,证实为内皮细胞。实验表明,BMSCs在体外分离和定向培养的ECs,经扩增后可能是心血管组织工程所需种子细胞的又一个重要来源。     

孕期应激对子代大鼠骨髓淋巴干细胞发育的影响

孕期应激对子代产生的影响是多方面的,这种影响是复杂的。研究表明,出生前的应激经历可导致出生后子代长期的免疫功能改变。这些改变追其根源与骨髓淋巴干细胞的改变有关。本文综述了大鼠孕期经历应激的子代骨髓淋巴干细胞所受的影响及免疫系统的相关改变,并根据现有的研究提出假说,为进一步研究孕期应激导致子代免疫系统改变的机理研究提供新的思路。     

To cureleukemia and related conditions

In Vitro Cellular &; Developmental Biology - Plant -     

Role of Immunohistochemistry in Staging Diffuse Large B-cell Lymphoma (DLBCL)

The use of immunohistochemistry (IHC) in staging bone marrow in non-Hodgkin''s lymphoma (NHL) is largely limited to ambiguous cases, particularly those with lymphoid aggregates. Its role in routine clinical practice remains unestablished. This study aimed to determine whether the routine use of IHC in diffuse large B-cell lymphoma (DLBCL) would improve the detection of lymphomatous involvement in the bone marrow. It also sought to determine the impact of IHC on predicting survival compared with routine histological diagnosis using hematoxylin and eosin (H&E), Giemsa, and reticulin staining. The bone marrow trephines of 156 histologically proven DLBCL cases were assessed on routine histology, and IHC using two T-cell markers (CD45RO and CD3), two B-cell markers (CD20 and CD79a), and κ and λ light chains. IHC detected lymphomatous involvement on an additional 11% cases compared with histology alone. Although both routine histology and IHC were good predictors of survival, IHC was better at predicting survival on stepwise multivariate Cox regression analysis. IHC performed routinely on bone marrow trephines has the ability to improve detection of occult lymphoma in experienced hands. Furthermore, it is a better predictor of survival compared with routine histological examination alone. (J Histochem Cytochem 56:893–900, 2008)     

Racial differences in eggs and juveniles of Windermere charr, Salvelinus alpinus

At least four races of charr occur in Windermere, the largest natural lake in England: north basin and south basin autumn spawners, north basin and south basin spring spawners. This study examines racial differences between eggs and juveniles, and relates juvenile size and survival to egg size. There were no major differences between races for egg incubation times and the percentage of eggs hatching successfully, the latter being high (mean values 76–96%) with a negligible proportion of abnormal alevins (<0.8%). Although there were no significant differences in the lengths of the female parents, both eggs and alevins were significantly larger for the autumn spawners than the spring spawners. Size differences in alevins, especially live weight, were positively related to egg size but not female parent size. Mean percentage survival for juveniles attaining the independent feeding stage was higher for the progeny of autumn spawners (32%) than spring spawners (3%). Racial differences in the egg and alevin stages therefore appear to have a significant effect on subsequent survival, and could be ultimately responsible for the relatively small proportion of spring spawners (only 4–6%) in the Windermere population of charr.     

Methotrexate chemotherapy–induced damages in bone marrow sinusoids: An in vivo and in vitro study

Chemotherapeutic agents are very well evident extrinsic stimuli for causing damage to endothelial cells. Methotrexate is an antimetabolite commonly used to treat solid tumours and paediatric cancers. However, studies on the effect(s) of methotrexate on bone marrow microvascular system are inadequate. In the current study, we observed a significant bone marrow microvascular dilation following methotrexate therapy in rats, accompanied by apoptosis induction in bone marrow sinusoidal endothelial cells, and followed by recovery of bone marrow sinusoids associated with increased proliferation of remaining bone marrow sinusoidal endothelial cells. Our in vitro studies revealed that methotrexate is cytotoxic for cultured sinusoidal endothelial cells and can also induce apoptosis which is associated with upregulation of expression ratio of Bax and Bcl-2 genes and Bax/Bcl-2 expression ratio. Furthermore, it was shown that methotrexate can negatively affect proliferation of cultured sinusoidal endothelial cells and also inhibit their abilities of migration and formation of microvessel like tubes. The data from this study indicates that methotrexate can cause significant bone marrow sinusoidal endothelium damage in vivo and induce apoptosis and inhibit proliferation, migration and tube-forming abilities of sinusoidal endothelial cells in vitro.     

The Body Mass Index-Mortality Relationship in White and African American Women

Objective : To examine the association of body mass index to all-cause and cardiovascular disease (CVD) mortality in white and African American women. Research methods and procedures : Women who were members of the American Cancer Society Prevention Study I were examined in 1959 to 1960 and then followed 12 years for vital status. Data for this analysis were from 8,142 black and 100,000 white women. Body mass index (BMI) was calculated from reported height and weight. Associations were examined using Cox proportional hazards modeling with some analyses stratified by smoking (current or never) and educational status (less than complete high school or high school graduate). Results : There was a significant interaction between ethnicity and BMI for both all-cause (p<0.05) and CVD mortality (p<<0.001). BMI (as a continuous variable) was associated with all-dause mortality in white women in all four groups defined by smoking and education. In black women with less than a high school education, there were no significant associations between BMI mortality. For high school-educated black women, there was a significant association between BMI and all-cause mortality. Among never smoking women with at least a high school education, models using the lowest BMI as the reference indicated a 40% higher risk of all-cause mortality at a BMI of 35.9 in black women vs. 27.3 in white women. Discussion : The impact of BMI on mortality was modified by educational level in black women; however, BMI was a less potent risk factor in black women than in white women in the same category of educational status.