Regulation of the Bone Vascular Network is Sexually Dimorphic

Osteoblast (OB) lineage cells are an important source of vascular endothelial growth factor (VEGF), which is critical for bone growth and repair. During bone development, pubertal differences in males and females exist, but little is known about whether VEGF signaling contributes to skeletal sexual dimorphism. We have found that in mice, conditional disruption of VEGF in osteocalcin-expressing cells (OcnVEGFKO) exerts a divergent influence on morphological, cellular, and whole bone properties between sexes. Furthermore, we describe an underlying sexual divergence in VEGF signaling in OB cultures in vitro independent of circulating sex hormones. High-resolution synchrotron computed tomography and backscattered scanning electron microscopy revealed, in males, extensive unmineralized osteoid encasing enlarged blood vessel canals and osteocyte lacunae in cortical bone after VEGF deletion, which contributed to increased porosity. VEGF was deleted in male and female long bone–derived OBs (OBVEGKO) in vitro and Raman spectroscopic analyses of mineral and matrix repertoires highlighted differences between male and female OBVEGFKO cells, with increased immature phosphate species prevalent in male OBVEGFKO cultures versus wild type (WT). Further sexual dimorphism was observed in bone marrow endothelial cell gene expression in vitro after VEGF deletion and in sclerostin protein expression, which was increased in male OcnVEGFKO bones versus WT. The impact of altered OB matrix composition after VEGF deletion on whole bone geometry was assessed between sexes, although significant differences between OcnVEGFKO and WT were identified only in females. Our results suggest that bone-derived VEGF regulates matrix mineralization and vascularization distinctly in males and females, which results in divergent physical bone traits.     

Cultured human endothelial cells synthesize a plasma membrane protein complex immunologically related to the platelet glycoprotein IIb/IIIa complex

We have previously demonstrated that endothelial cells synthesize a plasma membrane protein indistinguishable from platelet glycoprotein (GP) IIa. The present study provides evidence for a further analogy between the platelet and the endothelial cell membrane by showing that cultured endothelial cells also synthesize a membrane protein complex immunologically related to the platelet GP IIb/GP IIIa complex. This evidence is based on the following observations: (1) C17, a murine monoclonal antiplatelet GP IIIa antibody, consistently precipitates two proteins, apparent molecular weights, respectively, 115,000 and 125,000 reduced and 95,000 and 135,000 nonreduced, from metabolically (35S- methionine) as well as surface 125I-labeled cultured human endothelial cells; (2) upon crossed immunoelectrophoresis of solubilized endothelial cells against a polyclonal rabbit antiplatelet antiserum and 125I-labeled C17 IgG, a single precipitate of the protein(s) recognized by C17 is observed. As judged by their mobility in 9% polyacrylamide gels, both endothelial proteins appear to have a somewhat larger molecular weight than their platelet counterparts. Patterns obtained by crossed immunoelectrophoresis are also indicative of a difference in electrophoretic behavior of the platelet GP IIb/IIIa complex and the endothelial cell protein complex.     

Eight-year follow-up of pulmonary function and oxygen uptake during exercise in 16-year-old males with cystic fibrosis

Eight of nine Norwegian 16-year-old males with cystic fibrosis, and six age-matched, physically active controls were included in an eight-year follow-up study, involving pulmonary and bicycle exercise testing. The individual's level of regular physical exercise was registered, and we investigated whether or not this could be correlated to changes in clinical status, lung function and maximal oxygen uptake. Four males with cystic fibrosis trained regularly for 4-7 h weekly, while the other four patients did no regular exercise. Three of the latter died during the study, and the fourth male in the non-training group deteriorated significantly during the study period of eight years. The four males in the training group showed improvement in lung function parameters and maximal oxygen uptake, but two of them had more marked obstructive lung disease after the age of 24 years. Even though the sample was small, and several other factors may influence the results, the study indicates that regular physical exercise has beneficial long-term effects on clinical status, lung function and physical fitness in adolescent cystic fibrosis males.     

Disseminated Histoplasmosis in a 13-year-old girl: a case report

Background

Disseminated histoplasmosis is a rare fungal infection and most documented cases are in immune-compromised individuals such as those with acquired immuno-deficiency syndrome.

Objective

To describe a case of disseminated histoplasmosis in an adolescent girl.

Method

We report a case of disseminated histoplasmosis in a 13-year-old adolescent girl. She was admitted for 16 days because of neck masses of 3 years duration, generalized body swelling of 3 months and reduction in urinary output of 2 months. She tested negative for human immunodeficiency virus antibodies.

Result

An autopsy was performed because a definitive diagnosis could not be made while the patient was still alive. The autopsy revealed central caseating areas in the lymph nodes and membranoproliferative glomerulonephritis. The periodic acid-Schiff staining technique for tissues showed viable yeast cells suggestive of histoplasmosis. Zeihl-Neelsen''s staining for mycobacteria tuberculosis was negative.

Conclusion

Undiagnosed case of disseminated histoplasmosis while the patient was alive is being reported in a 13-year-old girl. Disseminated histoplasmosis should be considered as a differential diagnosis of childhood chronic infections and malignancies as in Nigeria.