Kouhei Hashizume

A Female Infant Who Had both Complete VACTERL Association and MURCS Association : Report of a Case

A 41-day-old female infant with VACTERL association was transferred to the pediatric intensive care unit of our hospital. She had been delivered at 36 weeks gestation by spontaneous vaginal delivery and weighed 2340 g. Esophageal atresia type A with long gap, anal atresia, cardiac anomaly (atrial septal defect and patent ductus arteriosus), thoracic vertebral dysplasia, left renal agenesis, and minor anomalies (left-side facial nerve palsy, left-side difficulty in hearing, and the absence of the right thenar) had been diagnosed by various examinations. She was transferred to our hospital to receive treatment for heart failure due to a cardiac anomaly. We recognized vaginal atresia during a radical operation for anal atresia (rectovestibular fistula) at 8 months of age. Furthermore, magnetic resonance imaging (MRI) revealed agenesis of the uterus. MURCS association includes Mullerian duct aplasia or hypoplasia, renal aplasia, and cervicothoracic somite dysplasia. This is the first case of complete VACTERL association combined with MURCS association.

Pattern of FHIT gene expression in normal and leukaemic cells

Chromosomal aberrations and inactivation of tumour suppressor genes are frequent in acute leukaemia. To determine whether the FHIT gene is involved in the development of leukaemia, we examined the FHIT transcript in 65 leukaemia cell lines, 5 fresh acute leukaemia patients at diagnosis and in complete remission, normal peripheral blood lymphocytes obtained from 14 healthy volunteers and Epstein‐Barr (EB) virus transformed 5 B‐cell lines (EB‐lines), using nested reverse transcription‐polymerase chain reaction and direct sequencing. The transcripts were classified into 4 patterns: pattern I revealed the normal transcripts only, pattern II the altered transcripts in addition to the normal transcripts, pattern III the altered transcripts without the normal transcripts and pattern IV an absence of normal and altered FHIT transcripts. Nineteen cell lines were classified as pattern I, 32 as pattern II, 2 as pattern III and 12 as pattern IV. The frequency of loss of FHIT expression (pattern III or IV) varied in each type of leukaemia cell line; the order ranked from the highest incidence was acute myeloid leukaemia (AML), T‐cell acute lymphoblastic leukaemia (T‐ALL), B‐precursor ALL, B‐ALL, and chronic myeloid leukaemia (CML). No genomic rearrangement was found in any samples examined. All of 5 patients showed same pattern II FHIT transcripts at 2 different stages of the disease. All normal peripheral blood lymphocytes and EB‐lines were classified as pattern I or II. Our results suggested that patterns III and IV of FHIT transcripts might be associated with the development of a subset of leukaemia, while pattern II which has so far been reported as an aberrant transcript in varieties of malignant tumours might not be associated with leukaemogenesis. Int. J. Cancer 81:897–901, 1999.

XRASGRP2 is essential for blood vessel formation during Xenopus development.

Ras guanyl nucleotide-releasing protein 2 (RASGRP2), one of the Ras guanine exchange factors, is implicated as a critical regulator of inside-out integrin activation in human lymphocytes, neutrophils and platelets. However, the activities of this protein in endothelial cells remain unclear. In the current study, we identify a physiological function in blood vessel formation for XRASGRP2, which is the Xenopus ortholog of mammalian RASGRP2. XRASGRP2 over-expression induced ectopic vascular formation, and XRASGRP2-knockdown embryos showed delayed vascular development. We also investigated the upstream signaling of XRASGRP2 in endothelium formation. XRASGRP2 expression was up-regulated in the presence of VEGF-A and down-regulated following VEGF-A depletion. XRASGRP2 knockdown abolished the ectopic induction of endothelial cells by VEGF-A in the posterior ventral blood island. These results suggest that XRASGRP2 is essential for vascular formation during Xenopus development.

An experimental animal model of split cord malformation.

In this study, we examined an experimental animal model of split cord malformation (SCM) produced by the surgical induction of a fistula. In Cynopus pyrrhogaster neurulae (stage 18.5 ± 0.5), the neural plate was incised and divided to construct a fistula that mimicked a neurenteric canal. After the procedure, the development of these embryos was examined morphologically and histologically. Following incubation, hemicords, hemicords with their own heminotochords, and dermal sinus were observed in histological sections of embryos with an induced fistula. These abnormalities varied with the length and duration of the fistula, and the induction of this fistula apparently caused the development of this anomaly. The histological findings resembled the findings in human cases. The results of this study support the hypothesis that SCM may originate from an accessory neurenteric canal.