In vivo haematopoietic potential of human neural stem cells

The fetal sheep model was used to compare the in vivo haematopoietic potential of human neural stem cells (NSC) versus bone marrow (BM)-derived haematopoietic stem cells (HSC). To this end, sheep were transplanted with either 8 x 10(5) NSC (n = 11) or HSC, CD34(+)Lin(-) (n = 5), and subsequently analysed for haematopoietic chimaerism. While HSC-transplanted sheep displayed robust donor-derived haematopoiesis starting at less than 2 months post-transplant, NSC recipients exhibited haematopoietic engraftment at much later time points. Nevertheless, chimaerism persisted in both groups throughout the course of this study. Transplantation of secondary recipients with human CD45(+)/HLA-DR(+) cells from the BM of NSC primary recipients at 14 and 16 months post-transplant demonstrated that long-term engrafting HSC were present in these animals. At 6 months post-transplant, both NSC- and HSC-transplanted sheep were mobilised with granulocyte colony-stimulating factor. In contrast to HSC-transplanted animals, levels of human blood cells in peripheral blood of NSC-transplanted sheep remained low throughout mobilisation. Our results show that, although human NSC were able to give rise to multilineage haematopoiesis in our model, the levels, timing of blood cell production and the ability to respond to cytokine mobilisation were different, suggesting that human NSCs latent haematopoietic potential is inherently different from that of true HSC.     

Tumor necrosis factor alpha-induced endothelial tissue factor is located on the cell surface rather than in the subendothelial matrix

Because there is no consensus regarding the precise distribution of induced endothelial tissue factor (TF), we studied TF activity in and on tumor necrosis factor alpha-stimulated cultured human umbilical vein endothelial cells (ECs) and their underlying matrix. TF was mainly expressed on the cell surface. Only small traces were found on the apical surface suggesting that TF is predominantly located on the basolateral side of the cell membrane. The presence of TF on the cell surface was confirmed by flow cytometry. Subendothelial TF activity appeared to be dependent upon the procedure used to remove the stimulated EC monolayer. Whereas ammonium hydroxide or hypotonic lysis resulted in relatively high levels of matrix-associated TF, virtually no TF was found on the matrix after mild enzymatic detachment of stimulated ECs. Cell removal with EDTA resulted in intermediate levels of matrix-associated TF. Neither the enzymatic treatment nor EDTA degraded or removed this TF activity. Similar patterns were observed for matrix-associated TF antigen and EC surface markers. Electron microscopic analysis showed cell fragments on the matrix after monolayer lysis. The findings strongly suggest that induced endothelial TF associated with the subendothelial matrix actually represents TF on EC remnants.     

Maternal Hyperglycemia During Pregnancy Predicts Adiposity of the Offspring

OBJECTIVE

To investigate associations between maternal pregnancy hyperglycemia, gestational diabetes mellitus (GDM), and offspring adiposity.

RESEARCH DESIGN AND METHODS

We evaluated these associations in a longitudinal study of 421 mother-daughter pairs at Kaiser Permanente Northern California. Maternal pregnancy glucose values were obtained from maternal medical records. Outcomes included three measures of girls’ adiposity, measured annually: 1) ≥85th age-specific percentile for BMI; 2) percent body fat (%BF); and 3) waist-to-height ratio (WHR).

RESULTS

Adjusting for maternal age at delivery, race/ethnicity, pregravid BMI, girl’s age, and girl’s age at onset of puberty, having a mother with GDM increased a girl’s risk of having a BMI ≥85th percentile or having %BF or WHR in the highest quartile (Q4), compared with those in the lowest quintile of blood glucose (odds ratio [OR] 3.56 [95% CI 1.28–9.92]; OR 3.13 [95% CI 1.08–9.09]; and OR 2.80 [95% CI 1.00–7.84], respectively). There was a significant interaction between the presence of GDM and pregravid BMI; girls whose mothers had both risk factors had the highest odds of having a BMI ≥85th percentile (OR 5.56 [95%CI 1.70–18.2]; Q4 %BF, OR 6.04 [95%CI 1.76–20.7]; and Q4 WHR, OR 3.60 [95%CI 1.35–9.58]). Similar, although weaker, associations were found in the association between hyperglycemia and offspring adiposity.

CONCLUSIONS

Girls who were exposed to maternal GDM or hyperglycemia in utero are at higher risk of childhood adiposity; risk increases if the mother is overweight or obese. Screening and intervention for this high-risk group is warranted to slow the intergenerational transmission of obesity and its sequelae.     

N-(1-乙氧羰基-3-苯氨甲酰基丙基)甘氨酰甘氨酸衍生物的合成

报道4个N-(1-[1-乙氧羰基-3-(对甲)苯氨甲酰基]丙基甘氨酰｝-N-取代甘氨酸(XI_1～4)和5个1-[1-乙(或甲)氧羰基-3-(对甲)苯氨甲酰基]丙基-4-取代-1,4-哌嗪-2,5-二酮(XII_1～5)共9个估计有血管紧张素转化酶抑制活性化合物的合成和鉴定。所有这些化合物及9个相应的酯(X_1～9)均未见文献报道。药理初试结果,化合物XII₂,XII₅,XI₄和XII₁均有较强降压活性。     

Hematopoietic growth factors: overview and clinical applications, Part I

The growth and differentiation of blood cells is regulated by a group of at least 12 glycoproteins, collectively known as hematopoietic growth factors. Advances in protein biochemistry and molecular genetics have provided the tools for the bulk production of these hormones for clinical application. Clinical trials of macrophage colony-stimulating factor, granulocyte macrophage colony-stimulating factor, granulocyte colony-stimulating factor, and interleukin-3 have all demonstrated significant effects on the peripheral blood counts of the recipients. The clinical usefulness of these agents in ameliorating post-chemotherapy myelosuppression, in the treatment of other cytopenias, and in enhancing engraftment after bone marrow transplantation has already been demonstrated. Potential applications to the therapy and diagnosis of other clinical disorders is under study. The history of the elucidation of these growth factors, our current understanding of their properties, interactions, and clinical effects, and the potential prospects for their future use in the manipulation of human blood cell production are the subject of this review.