Extracellular vesicle‐mediated MFG‐E8 localization in the extracellular matrix is required for its integrin‐dependent function in mouse mammary epithelial cells

Milk fat globule‐EGF factor 8 (MFG‐E8) is a divalent‐binding secretory protein possessing an Arg‐Gly‐Asp (RGD) motif and a phosphatidylserine (PS)‐binding motif. This protein has been shown to be involved in mammary gland development and morphogenesis. Integrin‐binding activity is necessary for these MFG‐E8‐dependent cell processes. Although the target cells and molecules of MFG‐E8 in the cellular microenvironment are important to understand its physiological function, its localization is largely unclear. Here, we found that mouse MFG‐E8 localized to the basal lamina of the mammary gland during involution. In a model system of mammary COMMA‐1D cells, exogenously and endogenously expressed MFG‐E8 was deposited in the extracellular matrix (ECM) with membranous particles dependently on the PS‐binding motifs in the discoidin domains that were essential for association ability to extracellular vesicles (EVs). These data showed the basal MFG‐E8 localization mechanism in which EVs served as a scaffold. Such an immobilized MFG‐E8 associating with cell substrata but not soluble one in the culture media promoted integrin‐dependent suppression of β‐casein expression. These results suggest that MFG‐E8 requires EVs to transduce cellular signals from the basolateral side of the adhesion cells by accumulating in ECM.     

Demonstration and distribution of tau‐positive glial coiled body‐like structures in white matter and white matter threads in early onset Alzheimer’s disease

The present report concerns the demonstration and distribution of tau‐positive structures in the frontal and temporal white matter of five autopsy cases of early onset Alzheimer’s disease (AD). The relationship between white matter lesions and tau positive structures was also investigated. Five early onset AD brains, which had not only unambiguous white matter lesions, but also no or rare atherosclerosis and minimal amyloid angiopathy, were examined. There were several tau‐positive coiled body‐like structures and many thread‐like structures in the white matter, although previous reports showed only a few coiled bodies in the white matter in the AD brain. No relationship was found between the degree of each white matter lesion and number or distribution of tau‐positive structures in the white matter. The results suggest that the AD brain has tau‐positive structures in the white matter similar to some neurodegenarative brain diseases such as progressive supranuclear palsy, corticobasal degeneration, and dementia with grains. However, tau abnormalities may have fewer effects when they are located in white matter lesions in AD.     

Osteogenesis imperfecta-like syndrome with severe mental retardation and extrapyramidal tract signs

We report a girl with a unique combination of malformations, including recurrent fractures, mental retardation with extrapyramidal tract signs and minor facial abnormalities. Generalised osteoporosis with overtubulation of long bones was similar to that of osteogenesis imperfecta (OI). However, the short tubular bones were distinctively undertubulated and wormian bones were not found. Based on clinical, laboratory and neuroradiological examinations, it was less likely that bone fragility was attributable to disuse bone atrophy related to her physical handicap and the neurological abnormalities secondary to brain insult. She is presumed to have a previously undescribed OI-like syndrome. Received: 19 September 1997 Accepted: 15 May 1998     

Surgical repair of a distal arch aneurysm with a stent-graft

This study evaluates the effectiveness and potential complications of stent-grafting for the treatment of distal arch aneurysms using profound hypothermia and circulatory arrest with retrograde cerebral perfusion. Between December 1998 and December 2001, 9 consecutive patients with a distal arch aneurysm (6 men and 3 women, mean age 71 years) underwent surgical repair using a stent-graft. Profound hypothermic circulatory arrest and retrograde cerebral perfusion were performed in all patients. Endovascular leakage was screened postoperatively using three-dimensional computerized tomography. The mean follow-up period was 27.4 months. Thirty day mortality was 0%. One patient died 3 months after stent-grafting due to proximal leakage into her aneurysm. The mean postoperative extubation period was 2.1 days. No patients suffered cerebral infarction or paraplegia. Although preliminary outcomes using this technique were good, endovascular leakage is a concern. We suggest that, if major proximal leakage is recognized postoperatively, re-intervention should be performed as soon as possible. Endovascular stent-grafting appears to be a good alternative treatment for distal arch aneurysms, although longer follow-up is necessary to more comprehensively evaluate this procedure.