Transient abnormal myelopoiesis in a cytogenetically normal neonate.

We present a cytogenetically normal neonate who developed transient abnormal myelopoiesis. The blasts showed trisomy 21. In contrast, fibroblasts, and PHA-stimulated peripheral blood demonstrated normal diploid line on extensive karyotyping. Direct sequencing of the DNA derived from the peripheral blood at overt disease revealed splice site mutation in the boundary of GATA1 exon 2. The patient received three courses of chemotherapy leading to complete remission. During the complete remission, there was neither mutation of GATA1 exon 2 nor trisomy 21, confirming somatic nature of both abnormalities. The patient is now free from the disease 12 months after remission. This case emphasizes the significance of trisomy 21 as the cause of transient abnormal myelopoiesis in Down syndrome.

Vascular endothelial cells and smooth muscle cells mediate carbachol-induced hepatocyte proliferation via muscarinic receptors and IP3/PKC signaling cascades.

An acetylcholine (ACh) agonist, carbachol (Cch), causes hepatocytes to proliferate in the presence of hepatic nonparenchymal cells (HNPCs). To identify the HNPCs and ACh receptor subtypes involved in carbachol-induced hepatocyte proliferation (CIHP), we examined two types of vascular cells as candidates for HNPCs mediating CIHP in cocultures of hepatocytes using the Transwell filter insert. In the coculture with vascular smooth muscle cells (VSMCs) or endothelial cells (VECs), but not in the monoculture, 72 h treatment with Cch significantly increased the numbers of hepatocytes. The results suggest that both VSMCs and VECs are involved in CIHP through soluble factors secreted from these cells. Interestingly, coculture with VECs, but not with VSMCs, markedly increased the number of hepatocytes, even in the absence of Cch. Cell proliferation assays using an analogue of thymidine, bromodeoxyuridine (BrdU), demonstrated that the hepatocytes in both cocultures transiently replicated their chromosomes 12 h after Cch administration. Blocking the muscarinic type 1 ACh receptor (M1), M3/5, intracellular inositol triphosphate (IP3) receptor, or protein kinase C (PKC) pathways inhibited VSMC-mediated CIHP, whereas blocking the M3/5, IP3 receptor, or PKC pathways inhibited VEC-mediated CIHP. Co-culturing hepatocytes with both types of vascular cells markedly increased their albumin content, but addition of Cch had no effect. In conclusion, VSMCs among vascular cells mediate CIHP through M1, M3/5, and IP3/PKC signal transduction pathways, whereas VECs do so through M3/5, and IP3/PKC pathways.

Tigroid pattern of the white matter: a previously unrecognized MR finding in lissencephaly with cerebellar hypoplasia.

Brain MR images of a 14-month-old boy with lissencephaly and cerebellar hypoplasia showed numerous radiating linear structures in the white matter. This finding was identical to the tigroid or leopard-skin pattern that is seen in Pelizaeus-Merzbacher disease or metachromatic leukodystrophy and represents the perivascular white matter spared from demyelination. We speculate that mutations of the reelin gene, expressed both in the cortex and in the white matter, may play an important role in its development.