Background TrkA mRNA expression has been reported to be related to favorable outcome of neuroblastoma (NB). Previously, we found that interferon‐γ (IFN‐γ) can enhance TrkA mRNA expression in NB cell lines. In the present study, we examined the effect of nerve growth factor (NGF) on IFN‐γ‐induced TrkA protein to clarify the relationship between TrkA and cell differentiation of NB. Procedure The effect of IFN‐γ on the TrkA mRNA expression was screened in six human NB cell lines and a freshly prepared sample, SK‐rib, from a stage IV patient. Using two of them, we examined their morphological change during simultaneous loading of NGF and IFN‐γ. Tyrosine phosphorylation pattern after 5 min of NGF stimulation was also examined in immunoblot analysis with anti‐gp140trkA antibody and antiphospho tyrosine antibody. Results After a 4‐day treatment with 500 IU/ml IFN‐γ, TrkA mRNA increased in five cell lines and SK‐rib cells in association with growth inhibition. Although the degree of morphological differentiation did not increase in proportion to the TrkA expression induced by IFN‐γ, continuous loading of both IFN‐γ and NGF caused marked morphological differentiation in a cultured KP‐N‐RT cell line and SK‐rib cells during 10 days. Moreover, 5 min of NGF stimulation after IFN‐γ treatment caused the phosphorylation of TrkA protein and downstream proteins. Conclusions IFN‐γ could induce the functional NGF receptor even in the aggressive phenotype of NB. Med. Pediatr. Oncol. 34:394–401, 2000. © 2000 Wiley‐Liss, Inc.

Three human neuroblastoma cell lines were examined to determine the effect of recombinant γ‐interferon (IFN‐γ) treatment on the expression of trk proto‐oncogene. Increased levels of trk proto‐oncogene mRNA were observed in two neuroblastoma cell lines (KP‐N‐RT and KP‐N‐SI(FA)) after IFN‐γ treatment. The levels of trk mRNA increased with growth inhibition and morphological change in a time‐ and dose‐dependent manner. The decreased level of N‐myc mRNA after IFN‐γ‐treatment in KP‐N‐RT was inversely correlated with trk mRNA. Our results suggest that IFN‐γ can modulate the signal transduction of nerve growth factor in human neuroblastoma cells.

Most patients with homozygous or compound heterozygous pathogenic ACO2 variants present with muscular hypotonia features, namely, infantile cerebellar-retinal degeneration. Recently, two studies reported rare familial cases of ACO2 variants presenting as complex hereditary spastic paraplegia (HSP) with broad clinical spectra. Here, we report the case of a 20-year-old Japanese woman with complex HSP caused by compound heterozygous ACO2 variants, revealing a new phenotype of episodic visual loss during febrile illness.

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Three cases are reported of the association of childhood onset of thoracic aortic calcification with mucocutaneous candidiasis, endocrine dysfunction and recurrent non-fungal pulmonary disease. The aortic calcification affects the thoracic aorta and the low lumbar aorta and common iliac arteries, sparing the mid-lumbar aorta and its major branches. Ischemic signs and symptoms of the head and neck and lower limbs are absent. This peculiar, slowly progressive vascular calcification, although unexplained to date, appears to be a non-random part of the more common candidiasis-endocrinopathy syndrome.