Kiyotake Hirayama

Replication asynchrony between homologs 15q11.2 cytogenetic evidence for genomic imprinting

SummaryReplication kinetics of the Prader-Willi syndrome critical region (15q11.2) was investigated in seven normal healthy adult females using RBG replication bands. Replication asynchrony between homologs 15q11.2 was identified consistently in about 40% of cells in all individuals. It was limited to the stages in which Xp22, Xp11, Xq13 and Xq24/26 were visible in the late-replicating X chromosome. This asynchrony suggested that replication timing overlapped between 15q11.2 and the early replicating R-bands of the late X chromosome in some cells, and that the difference in replication timing between homologs was probably related to genomic imprinting; the latter has been suggested as a pathogenetic basis of Prader-Willi syndrome. As a result of an analysis of the proportions of asynchronous and synchronous cells in each replication stage, two types of cells were deduced providing 1∶1 methylation mosaicism of genomic imprinting was assumed. The first type was composed of cells with normal replication in one homolog and delayed replication in the other. The second type was composed of cells with normal replication in both homologs. Our results provide cytogenetic evidence of methylation mosaicism for mammalian genomic imprinting.

Iron status of newborns born to iron deficient anaemic mothers.

Haemoglobin, serum iron, total iron binding capacity, and serum ferritin were determined in newborns of 16 mothers with iron deficiency anaemia, 28 mothers with non-anaemic iron deficiency, and nine mothers with normal haemoglobin and serum ferritin levels. The results showed that there were no significant differences in the mean values of haemoglobin, serum iron, and total iron binding capacity among the newborns in the three groups. However, the mean value of serum ferritin differed significantly among the three groups, with the lowest values found in newborns of mothers with iron deficiency anaemia.

The costello syndrome: A boy with thick mitral valves and arrhythmias

SummaryA 3-year-old boy with Costello syndrome is reported. He had typical clinical features of the syndrome including severe postnatal growth retardation, poor sucking, mild developmental delay, a coarse characteristic facies, thick and loose skin of the hands and feet, sparse and curly hair, dark skin, and relative macrocephaly but lacked nasal papillomas. In addition, he had cardiac anomalies with extrasystoles and thick mitral valve tips. Mitral valve defects may be a clinical feature of the syndrome.

Trisomy 9q3 syndrome: a case report and review of the literature

A girl with partial trisomy 9q is reported. She was characterized by dolichomorphism, abnormalities of the digits, a cardiac defect and craniofacial dysmorphism. A high‐resolution analysis revealed the karyotype to be: 46,XX,‐3,+der(3)t(3;9)(q29;q13) de novo. A phenotype‐karyo‐type correlation study in 22 cases of partial trisomies 9q supported the delineation of a trisomy 9q3 syndrome. The smallest region of overlap was confined to 9q32.

16q21 Is critical for 16q deletion syndrome

A 1‐year‐old girl with an interstitial deletion of the long arm of chromosome 16 is reported. She was characterized by a distinct craniofacial dysmorphism, meningoencephalocele, mild hydrocephalus, short neck, broad great toes and abnormally positioned toes. High resolution GTG and RBG banding analyses revealed a karyotype: 46,XX,del(16) (q13q22) de novo. An analysis of the smallest region of overlap revealed that the critical band region for 16q deletion syndrome is 16q21.

Cardiovascular effects of Acanthaster planci venom in the rat: Possible involvement of PAF in its hypotensive effect

Cardiovascular effects of the crowns-of-thorns starfish (Acanthaster planci) venom were examined in rats. The crude venom extracted from the spines of A. planci caused systemic hypotension associated with an increase in heart rate and a decrease in renal cortical blood flow when given i.v. The hypotensive effect of the venom was not inhibited by pretreatment with atropine, indomethacin or aprotinin, but was significantly inhibited by SRI 63-441, a platelet activating factor (PAF) antagonist. The venom caused dose-dependent vasorelaxation of the isolated rat aortic ring preparation precontracted by noradrenaline, an effect which was significantly attenuated by pretreatment with SRI 63-441, methylene blue or parabromophenacyl bromide. Denudation of the endothelium also diminished the vasorelaxing effect of the venom. Both the vasorelaxing and the hypotensive effects showed tachyphylaxis. These results suggest the release of PAF or a PAF-like substance from the endothelium by the venom.

Zellweger syndrome and a microdeletion of the proximal long arm of chromosome 7

SummaryA 16-day-old girl with Zellweger syndrome and a chromosomal rearrangement, 46,XX,del(7)(q11.22q11.23), is reported. The diagnosis was confirmed by marked deficiencies of peroxisomal β-oxidation enzymes and dihydroxyacetone phosphate acyltransferase activities in rectal cells and fibroblasts obtained by biopsy and in hepatic cells obtained at autopsy. This is the first report of Zellweger syndrome associated with a chromosomal arrangement, a microdeletion of chromosome 7. A tentative gene assignment to 7q11 is suggested.

Haemodynamic and haematologic effects of Acanthaster planci venom in dogs

This study was designed to examine haemodynamic and haematologic effects of the crown-of-thorns starfish venom (Acanthaster planci venom: APV) in dogs. Severe systemic hypotension, thrombocytopenia and leukopenia were induced by APV (1.0 mg protein/kg i.v.), followed by gradual return to the baseline level within 60 min. Hypotension was presumably caused by two factors: an early decrease in systemic vascular resistance and the large reduction in cardiac output due to reduced ventricular filling. Indomethacin, a cyclooxygenase inhibitor, remarkably suppressed systemic hypotension induced by APV. The peak reduction in systemic pressure was associated with concomitant rise of plasma 6-keto-PGF1 alpha, a major stable metabolite of prostacyclin. Thus, the hypotensive effect of APV may be caused primarily by prostacyclin and/or some vasodilating prostaglandins. In contrast, thrombocytopenia and leukopenia were not affected by cyclooxygenase inhibitor, 5-lipoxygenase inhibitor or platelet activating factor (PAF) receptor antagonist. When APV was administered repeatedly, tachyphylaxis was developed in haemodynamic effects, but not in haematologic effects. These findings suggest that APV-induced hypotensive effects may occur mainly through endogenous production of vasodilating prostaglandins including prostacyclin, although APV-induced thrombocytopenia and leukopenia may be caused by other mechanism(s) unrelated to arachidonate metabolites and/or PAF.

Partial trisomy of distal 8q derived from mother with mosaic 8q23.3→24.13 deletion, and relatively mild expression of trichorhinophalangeal syndrome I

SummaryA 17-month-old girl with a partial trisomy of distal 8q derived from her mother, who has a mosaic 8q23.3→q24.13 deletion, was studied. Both showed a relatively mild phenotype of trichorhinophalangeal syndrome I. The karyotype of the proposita was designated as: 46,XX,-8,+der(8),inv ins(8;8)(p23.1;q24.13q23.3)mat. Her phenotype was considered similar to that of her mother despite the trisomies of distal 8q. She seems to be the first example of a partial trisomy of distal 8q derived from a parent with an interstitial deletion of a distal 8q segment and trichorhinophalangeal syndrome I.

Effects of norepinephrine on hypoperfusion-reperfusion injuries in hearts isolated from normal and diabetic rats

Contractile and energy-metabolic functions were investigated in paced hearts isolated from normal (Normal) and streptozotocin-diabetic rats (DM) during hypoperfusion at 1 ml/min with or without 10(-6) M norepinephrine (NE) and during reperfusion at the pre-hypoperfusion flow. Left ventricular pressure (LVP) and contractile force (CF) were monitored, respectively, through a water-filled balloon in LV and through a hook attached to the apex. A 1-h hypoperfusion without NE caused significant elevations in resting LVP and resting CF only in DM hearts, smaller transmural lactate accumulations in DM hearts, and similar ATP decreases in both groups. Significant decreases in developed LVP and developed CF were observed in both groups. NE during hypoperfusion caused deterioration of these cardiac dysfunctions in both groups, particularly in DM hearts. A 1-h reperfusion caused elevations in resting LVP and resting CF with no recovery in developed CF in Normal hearts, while it caused partial recovery in resting and developed CF in DM hearts. Both groups showed similar partial recovery of ATP. NE during hypoperfusion improved the mechanical dysfunction during reperfusion in DM hearts, but there was a smaller recovery in ATP than in hearts without NE. In vivo insulin treatment in DM restored the cardiac functions to Normal levels. Thus, DM hearts were more vulnerable to hypoperfusion, while Normal hearts were more vulnerable to reperfusion injury.