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FIGURE 16.2
X-rays. Radiographs of the skull at age 1 year (A) demonstrate diminished calvarial mineralization and enlargement of the
calvarial vault. At birth, the chest (B) was small, the ribs were thin and some had healing fractures, one clavicle was bent, both humeral bones
had fractures, platyspondyly was present, and overall mineralization appeared diminished. By 1 year of age (C and D), the ribs had become
broad, platyspondyly was still apparent with diminished central mineralization of the vertebral bodies, and the humeral bones had a tubular
shape, thin cortices and diminished mineralization. The deformity and decreased mineralization of the bones in the arms are apparent at 1
year (E), and the minimal effect of pamidronate can be seen. At 1 month (F), 1 year (G) and 28 months (H), there is rhizomelic shortening and
limited modeling of the long bones with very thin cortices. The lines of increased mineralization reflect the successive pamidronate infusions.
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Reprinted with permission of the publisher.
retained in the ER of both fibroblast types cultured in the
absence of ascorbate, and were co-localized with HSP47.
In normal fibroblasts, 2 hours after the addition of ascor-
bate, most of the procollagen had disappeared from
the cells, while in the OI fibroblasts abnormal procolla-
gen molecules and HSP47 were still retained in the ER.
However, unlike studies reported below, these authors
found increased HSP47 in OI fibroblasts demonstrated
by immunoprecipitation.
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To determine the effect of decreased HSP47 on the
type I procollagen triple helix, Christiansen et al. also
examined the protease sensitivity of the secreted pro-
collagen. The triple-helical domain of type I procol-
lagen secreted by control cells was protease resistant at
37°C but the chains were degraded very rapidly when
denatured at 50°C prior to protease treatment. In con-
trast, type I procollagen secreted from patient cells was
cleaved asymmetrically within the triple-helical domain
when digested for 1 min at 37°C with a combination of
trypsin and chymotrypsin. These results illustrate the
function that HSP47 normally assumes in determining
the final integrity of the triple helix.
