Members of the Eph receptor tyrosine kinase have previously been implicated in cranial neural tube development. Failure of neural tube closure leads to the devastating conditions known as anencephaly and spina bifida. EphA2 and EphA4 are expressed at the tips of the closing spinal neural folds prior and during neural tube closure. We investigated the possible role of murine EphA2 and EphA4 during the last step of primary neural tube closure, which is adhesion and fusion. The individual mouse knockouts of EphA2 and EphA4 per se do not exhibit neural tube defects (NTDs). The embryos generated by the crossing of double heterozygotes Epha2tm1Jrui/+Epha4rb-2J/+ displayed NTDs with a wide degree of severity including close exencephaly and close spina bifida (spina bifida occulta). Interestingly, mutants displaying NTDs had skin covering the underlying lesion. The tissue sections revealed the elevated neural folds had not adhered and fused. The phenotypes seen in Epha2tm1Jrui/+Epha4rb-2J/+ double heterozygous embryos suggest both genes play a compensatory role with each other in the adhesion and fusion of the neural tube. In this study, there exists a >50% penetrance of NTDs in the mouse mutants, which genetically have a single allele each of EphA2 and EphA4 absent.
2a 2b dihomo 15(S) 15 methyl PGF2 alpha methyl ester (dihomo 15 me PGF2 alpha) in intramuscular doses of 0.5 mg 8 hourly was used in 631 patients with abnormal intrauterine pregnancy comprising 282 cases of intrauterine fetal death, 233 cases of missed abortion, 34 and 82 cases respectively anencephalic and molar pregnancies. The study was carried out as a collaborative project between the University Departments of Obstetrics and Gynaecology in Singapore (Singapore), Medan (Indonesia) and Kuala Lumpur (Malaysia) during the period June 1974 and November 1979. Six hundred patients (95.1%) aborted or delivered in a mean time of 11.3 hours (S.D. +/- 7.0) with an average of 1.8 injections of the prostaglandin analogue per patient. Side effects included vomiting (23.6%; mean 0.45 episodes per patient), diarrhoea (44.4%; mean 1.00 episode per patient), cold and shivering (11.9%) and pyrexia (12.4%). One patient sustained a cervical laceration which did not require repair. There were no complications.