Matteo Adinolfi

IMMUNOGENICITY OF HUMAN AMNIOTIC EPITHELIAL CELLS AFTER TRANSPLANTATION INTO VOLUNTEERS

Human amniotic epithelial cells do not express on their surfaces HLA-A, B, C, and DR antigens, or beta 2-microglobulin. In vitro these cells synthesise the enzymes lacking in patients with selected enzymatic deficiencies: the survival of a transplanted monolayer of human amniotic epithelial cells was therefore investigated in seven volunteers. None of the volunteers showed clinical signs of acute rejection, and amniotic epithelial cells were demonstrated by biopsy up to 7 weeks after implantation. HLA antibodies were not detected in samples of serum from four volunteers thoroughly investigated, and there was no in-vitro lymphocyte reaction to the amniotic cells in two of them. The results suggest that acute immune rejection does not occur after the transplantation of human amniotic epithelial cells.

The development of the human blood-CSF-brain barrier.

At present there is much concern about the exposure of the fetus to environmental pollutants, food additives and drugs which, after reaching the fetal circulation from the mother, may affect the brain at stages in development when the central nervous system is particularly sensitive to toxic agents (Bradbury 1979, Adinolfi 1979). The problem is emphasised and made topical by the rediscovery that indeed the blood-cerebrospinal fluid (CSF) barrier is ‘immature’ during fetal and perinatal life and that, as a result, plasma proteins present in fetal CSF will reach the brain cells and any molecule which is capable of crossing the placenta from the maternal circulation has the intrinsic potential to gain access to the fetal brain.

Rapid molecular method for prenatal detection of Down's syndrome

We have evaluated a rapid method that allows prenatal detection of Downs syndrome in less than 24 hours. DNA from uncultured amniotic fluid, fetal blood, and tissue samples was amplified with the small tandem repeat (STR) marker D21S11. Quantitative analysis of fluorescent STR products with evaluation of their sizes provided clear evidence for trisomy 21. Whilst most normal samples showed two amplification peaks of equal size, Downs syndrome samples were characterised by either three STR peaks or two peaks with a ratio of 2:1. Co-amplification with a non-polymorphic sequence allowed analysis of samples that were homozygous for the 21-derived STRs.

Neural Tube Defects in Curly-Tail Mice. II. Effect of Maternal Administration of Vitamin A

Vitamin A, a known teratogen of the central nervous system, was administered in various doses, at the time of active neural tube closure, to pregnant curly-tail mice which have a genetic predisposition to neural tube defects (n. t. d. ), and to A Strong mice, which are not so predisposed. The curly-tail mice showed an enhanced susceptibility to the teratogenic effect of vitamin A given on day 8 of gestation, demonstrating a clear gene─environment interaction. There was a differential response by the two sexes. Females seemed to be more affected by the vitamin A than males. When vitamin A was administered on day 9, instead of day 8, of gestation, the incidence of n. t. d. decreased rather than increased. Furthermore, the number of mice affected by n. t. d. was markedly lower even than that found spontaneously in untreated curly-tail mice.

Neural tube defects in curly-tail mice. I. Incidence, expression and similarity to the human condition

The incidence of neurovertebral defects in mutant mice of the curly-tail strain was investigated and found to be similar to that observed in the same mice twenty-five years ago. The results of breeding experiments support the hypothesis of Grüneberg that the defects in these mice are probably caused by a recessive gene, the expression of which is markedly affected by the genetic background. Selection against the curly-tail phenotype for six generations did not affect the incidence of abnormalities. A marked excess of females was found among exencephalic mice, as among humans with neural tube defects. Similarly, polyhydramnios, hydrocephaly, high levels of amniotic fluid alphafoetoprotein and distinctive, rapidly adhering cells in the amniotic fluid also occurred in these mice, as in humans. The curly-tail mice thus provide a useful model for the investigation of neural tube defects in man.

Detection of trisomy 18 and Y-derived sequences in fetal nucleated cells obtained by transcervical flushing

A procedure which combines the collection of fetal cells by transcervical flushing and in situ hybridisation techniques on nuclei in interphase was used to detect trisomy 18 in a fetus at 12 weeks of gestation. Using a primed in situ labelling method, we could also detect Y-specific sequences in a small percentage of transcervically flushed cells obtained at 8-12 weeks from pregnant women with male fetuses. This approach seems to be suitable for prenatal diagnosis of major chromosomal abnormalities and other selected inherited disorders very early in gestation.

SERUM α1-FETOPROTEIN IN PATIENTS WITH LIVER DISEASE

Abstract A survey using immunodiffusion techniques for the detection of α 1 -feto-protein in 262 adult patients with various types of liver disease revealed the presence of the protein in 14 out of 35 patients with hepatocellular carcinoma; α 1 -fetoprotein was absent in all the other patients. Analysis on the basis of geographic localities of origin of the positive patients showed that 5 out of 17 were of British origin, 5 out of 8 of West African origin, and 4 out of 10 from other regions. These results, taken in conjunction with other surveys, suggest that regional differences may exist in the frequency of positive tests in patients with hepatocellular carcinoma.

NEUROLOGICAL HANDICAP AND PERMEABILITY OF THE BLOOD-CEREBROSPINAL FLUID BARRIER DURING FETAL LIFE TO MATERNAL ANTIBODIES AND HORMONES

doubt of the superiority of specialised care, but such a group is far smaller than the 12 per cent that was admitted. Because of mother-baby separation and other problems, unnecessary admission is unlikely to be in the babys interest and, as this survey shows, babies between 2001g and 2500g birthweight can and are looked after successfully at home and in GP units. Here we are up against one of the basic problems of modern medicine: how can we ensure that effective interventionist techniques are employed only when required and are not used so widely that they become a source of iatrogenic morbidity? One of the great values of the perinatal surveys is that they give us a clear picture of current practice, and some strong hints about its effectiveness. Let us hope that the evidence of this latest survey will lead to changes in practice.

The curly-tail mouse: An experimental model for human neural tube defects

Abstract Many aspects of the open lesions of the neural tube observed in the curly-tail mice are similar to those seen in man. In the mouse, the cause of the defects is a recessive gene, the expression of which is modified by the rest of the genome. A marked interaction between genetic and environmental factors was also observed in this strain of mice, thus suggesting that it represents a useful model to investigate the origin of the neural tube defects (NTD) in man. In the mutant strain, the interaction between the curly-tail gene and the environmental factors has been investigatigated using known teratogenic compounds, as well as hormones and vitamins, which it was hoped would prevent the malformations. An intriguing result was to observe that, while, as expected, excess of vitamin A increases the incidence of NTD, low doses, given at a particular stage of gestation, prevent the manifestation of the abnormalities. To investigate further the interaction between genetic and environmental factors and to provide some insight into the mechanisms underlying NTD in man, the effects of Trypan blue, hydroxyurea, progesterone, cortisone and vitamin E were also investigated in curly-tail mice and the results reported in this review.

Genetic control of H-Y synthesis. A hypothesis

SummaryIn view of the claimed serological H-Y positivity observed in patients with ovarian dysgenesis (for example, 45,X) and in XO mice (neither of whom have a Y chromosome), it is suggested that genetic control is exercised over the H-Y system by structural genes on the pairing segments of the X and Y chromosomes, acting on an autosomally coded H-Y precursor.