A cloverleaf skull syndrome probably of Beare-Stevenson type associated with Chiari malformation.

A case of cloverleaf skull (CLS) syndrome with Chiari malformation was reported. The patient developed congenital hydrocephalus, upper airway obstruction and breath holding spells. Ventriculo-peritoneal shunt improved the hydrocephalus, but the patient progressively developed apneic episodes in spite of intubation. Brain magnetic resonance imaging (MRI) disclosed severe Chiari malformation. Laminectomy of the cervical vertebrae and craniectomy at the occipital bone were performed to relieve the brain stem compression. Postoperatively, the respiratory symptoms improved slightly, but 8 weeks later the patient suddenly died. Literature survey revealed that this is the second case report of CLS associated with Chiari malformation. It was assumed that the respiratory problems in our patient are ascribable to the Chiari malformation as well as the upper airway obstruction. The patient here reported seems to be a case of Beare-Stevenson cutis gyrata syndrome, in view of an association of multiple characteristic dysmorphic features, in addition to CLS.

Regulation of pituitary growth hormone-releasing factor (GRF) receptor gene expression by GRF.

We examined how growth hormone-releasing factor (GRF) regulated pituitary GRF receptor gene expression in the conscious rat. GRF receptor mRNA levels were significantly increased by immunoneutralization of endogenous GRF with its specific antiserum. This effect was dose dependent and the maximum level was 3.8-fold higher than that in control rats. A similar rise in GRF receptor gene expression was obtained by the depletion of noradrenaline, a neurotransmitter thought to stimulate GRF release, and was reversed by 87% by the repeated administration of synthetic GRF. These results indicate that pituitary GRF receptor gene expression was up- or down-regulated in vivo in the absence or presence of GRF, respectively.

Growth of macroscopic human megakaryocyte colonies from cord blood in culture with recombinant human thrombopoietin (c-mpl ligand) and the effects of gestational age on frequency of colonies.

We investigated the effects of recombinant human thrombopoietin (rhTPO) on the growth of megakaryocytic (MK) colony derived MK progenitors from human cord blood (CB) in vitro and the effects of gestational age on the number of MK colonies. The results demonstrated that rhTPO alone supports the growth of MK colonies and induces not only proliferation but also differentiation of MK progenitors. CB shows a high frequency of MK colonies; most of which are very large and equivalent to high proliferative potential colony-forming unit-megakaryocyte. The colonies could be macroscopically observed as white spots in the culture dish. Preterm neonates showed greater numbers of MK progenitors than term neonates and there was an inverse correlation between gestational age and concentration of MK progenitors of CB. The effects of gestational age was an important factor on the proliferative capacity of MK progenitors and on the response to rhTPO.

Thyroid hormone regulation of gene expression of the pituitary growth hormone-releasing factor receptor.

To examine thyroid hormone regulation of the pituitary receptor for hypothalamic growth hormone (GH)-releasing factor (GRF), we studied effects of hypothyroidism on the pituitary GRF receptor (GRF-R) mRNA and its related parameters in rats. Thyroidectomy (Tx) induced a 61-65% reduction in GRF-R mRNA levels, which was significantly reversed with thyroxine (T4) replacement for 5 days at a dose of 1 microgram/100 g/day. Pituitary GH contents changed parallel to GRF-R mRNA levels following the Tx and T4 replacement. In contrast, Tx enhanced GRF release > 2 fold, which was not reversed with the regime of T4 replacement. These results indicate that thyroid hormone promotes pituitary GRF-R gene expression, not by modulating GRF secretion, but by acting on the pituitary directly. The decline in GRF receptor expression would contribute to somatotroph failure by rendering the pituitary refractory to the increased GRF signal in hypothyroidism.

Perinatal intracranial hemorrhage due to severe neonatal alloimmune thrombocytopenic purpura (NAITP) associated with anti-Yukb (HPA-4a) antibodies.

Neonatal alloimmune thrombocytopenic purpura (NAITP) is one of the causes of thrombocytopenia in the newborn period. The thrombocytopenia is caused by maternal transplacental antiplatelet alloantibodies. We report a case of NAITP in a newborn infant having subarachnoid hemorrhage. Examination of platelet antibodies revealed anti-Yukb, that is, human platelet antigen (HPA)-4a incompatibility. Cranial ultrasound and brain magnetic resonance imaging revealed subarachnoid hemorrhage in the temporal region inferior to the cephalohematoma. The lesion seemed to have been sustained during delivery. The patient was treated with high-dose gamma-globulin and several transfusions of random donor platelets and showed a good clinical course. This is the second reported case of NAITP associated with the Yuk antigen system having intracranial hemorrhage.

Structure and expression of the gene responsible for the triplet repeat disorder, dentatorubral and pallidoluysian atrophy (DRPLA).

Dentatorubral and pallidoluysian atrophy is associated with expansion of an unstable CAG repeat on chromosome 12p. We have determined the nucleotide sequences of overlapping cDNA clones and deduced the gene structure. The gene is ubiquitously expressed to form a single 4.5 kb transcript and encoded by an open reading frame of 1184 amino acids (aa), in which a polyglutamine track with variable length starts at aa 484. Although the predicted amino acid sequence does not reveal any function, it does contain several interesting motifs consisting of a simple repeated amino acid sequence, a homo-proline track, two stretches of arginine-glutamic acid dipeptides and a stretch of alternative histidine residues. These results provide clues toward understanding neurodegenerative diseases associated with triplet repeat expansion.

Dentatorubral and pallidoluysian atrophy expansion of an unstable CAG trinucleotide on chromosome 12p.

Dentatorubral and pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder characterized by combined systemic degeneration of the dentatofugal and pallidofugal pathways. We investigated a candidate gene and found that DRPLA patients had an expanded CAG trinucleotide repeat in a gene on the short arm of chromosome 12. The repeat size varied from 7-23 in normal individuals. In patients one allele was expanded to between 49-75 repeats or occasionally even more. Expansion was usually associated with paternal transmission and only occasionally with maternal transmission. Repeat size showed a close correlation with age of onset of symptoms and disease severity. We conclude that DRPLA is the seventh genetic disorder known to be associated with expansion of an unstable trinucleotide repeat.