Biomedical subjects
Publications and source records attributed to T Webb.
During the course of a population study of non-specific mental retardation in school-age males, a 13-year-old boy was ascertained. Cytogenetic studies revealed the presence of a fragile site at chromosome 22. The site was found to be both folate-dependent and heritable. The possibility that the presence of this fragile site is linked to mental retardation is discussed.
A fourth human blood group chimaera studies in Birmingham is an example of haemopoietic (twin) chimaerism in which the subject was unaware of being a twin. Chimaerism was discovered during routine antenatal serological investigation in which it was shown that the proposita has two red cell populations, one of the rhesus genotype rr, and the other R1r. Further studies showed that she has two populations of lymphocytes, one with the female karyotype, 46XX, and the other with the male karyotype, 46XY. Skin fibroblasts were all 46XX.
Blood samples were collected from 22 patients with Huntington's chorea and from 22 matched controls. Lymphocytes were separated from aliquots of each sample and cultures set up both from these and from further aliquots of whole blood. After 24 hours, half of each culture was subjected to X irradiation. Seventy-two hours later the percentages of live lymphocytes were estimated for each half of every culture and the viability ratio calculated for each sample. The lymphocytes derived from the patients with Huntington's chorea were found to be more susceptible to X irradiation than were the lymphocytes derived from controls. This was true both for whole blood and separated lymphocyte cultures. This susceptibility was found not to be the result of the main types of medication received by the patients. The small differences between viability ratios from patients and controls and the degree of overlap makes this test unsuitable for the prediction of asymptomatic carriers of the Huntington's chorea gene.
A clinical and cytogenetic study has been made of subjects from families who have possible X linked mental retardation. The families were distinguished as those with a clinical diagnosis of Renpenning syndrome and those with other behavioural or physical abnormalities obviating such a diagnosis. All subjects with REnpenning syndrome carried a fragile Xq27-28 chromosome in more than 4% of their blood lymphocytes. In addition, two other families who did not have Renpenning syndrome but had similar clinical features also carried the fragile site Xq27-28. A female age effect was observed and one possible carrier of Renpenning syndrome exhibited the fragile X in 10% of her lymphocytes but was also mentally retarded. Subjects within the same family did not always exhibit the fragile site on a comparable proportion of their cells.
Samples of human amniotic fluid from 48 pregnancies were examined by high resolution two-dimensional gel electrophoresis and the positions of the major peptides were mapped. Many of the proteins in amniotic fluid also occur in adult and fetal serum. Three regions in the amniotic fluid maps could be defined containing peptides which were not found in adult or fetal serum. The concentration of these peptides is variable and their origin is as yet unknown. Many differences were seen between adult and fetal serum proteins.
In the course of a study of the close linkage between the gene locus for the autosomal recessive disease, Congenital Adrenal Hyperplasia (CAH), and the major histocompatibility complex (MHC), a cytogenetic survey was undertaken. In one family, where a crossover might have occurred between some loci in the MHC complex and the locus for the 21-hydroxylase gene, there was also a crossover between the MHC locus and the centromere of chromosome 6.
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The long-term effectiveness of rubella vaccination in childhood is particularly important because the ultimate goal of immunization is the prevention of infection during pregnancy. Of 25 healthy children tested 4 to 5 years after rubella vaccination, 19 showed no evidence of cell-mediated immunity (CM) to rubella virus despite the presence of hemagglutination-inhibition or complement-fixation antibodies or both. Twenty-two of 25 seropositive, naturally infected young adults showed evidence of CMI. These results indicate that fetuses of women who have been vaccinated against rubella may not be protected against damage by wild rubella infection during the pregnancy, when CMI is physiologically depressed.
Lines of hybrid cells were established by fusion of mouse LMTK- cells with SV40 transformed human fibroblasts. The lines were examined for the presence of SV40 'T' antigen and the human chromosomes they carried identified by Giemsa banding. No significant correlation could be found between any particular human chromosome and the presence of SV40 virus.
Lines of fibroblasts have been established from normal individuals and from patients diagnosed as suffering from one of the mucopolysaccharidoses or mucopolysaccharide-storage diseases. Transformation of these lines with SV40 virus has been found to reduce their capacity to secrete sulphated mucopolysaccharides into the growth medium. No differences were detected between the individual cell types in their secretory capacity, either before or after viral transformation. A direct relationship was found to exist between the rate of acid mucopolysaccharide production and cell-doubling time. The level of sulphated mucopolysaccharide detected within the cell was also reduced for all cell types after transformation by SV40. Transformed fibroblasts from mucopolysaccharidosis patients, however, showed a relatively greater reduction in storage capacity than those derived from normal individuals.
A comparative study has been made of fibroblasts obtained from patients with differing susceptibilities to malignant disease, both with respect to their chromosome complements and their transformation with SV40 virus. Fibroblasts from 2 Bloom's syndrome patients were found not to have raised SV40 transformation rates and no correlation was found between chromosome abnormality per se and transformation. Of 2 cell types with greatly increased rates, one was derived from a neurofibromatosis patient and the other from an A-T heterozygote. When SV40 DNA was employed as the transforming agent for the latter, the transformation rate was no longer raised.
The ability of crude, semi-purified, and purified rubella antigens to elicit a specific and significant blast cell transformation of lymphocytes from immune individuals was investigated in 25 seronegative and 25 seropositive young adults. The type of preparation and the purity of the antigens were critical. Titration of the antigens by complement fixation or hemagglutination was of little value for selecting the best antigen which was a whole virion-purified antigen.
Chromosome analyses are reported for 14 lines of fibro-blasts derived from 8 ataxia-telangiectasia (ATT) patients and for 14 lines of control cells. An elevated incidence of chromosome damage including gaps and breaks, rings, dicentrics and fragments, and chromosome figures has been found to occur in ATT cells. Similar abnormalities present in different cell lines suggest that common break points occur in ATT fibroblast chromosomes. The SV40 virus transformation rates found for ATT cells lie within the range found for normal cells, and there is no direct correlation between the degree of chromosome damage exhibited by any ATT cell line and its transformation rate with SV40.
The extent of binding of 125I-Con A to the surface of SV40-transformed human fibroblasts and the degree of agglutination of the cells by the native lectin have been measured. In addition, trypsinized and succinylated Con A have been used to study the effects of the lectin upon certain cell growth parameters. Trypsinized Con A was found to alter the growth rate, the saturation density and the contact inhibition of the transformed cells, an effect not neutralized by alph-methyl-D-mannoside.
Fibroblasts derived from individuals with mucopolysaccharidosis, an inborn error of metabolism, have been found to be more easily transformed by simian virus 40 than are cells derived from normal individuals. The increased susceptibility does not seem to depend upon changes in glycoprotein at the cell surface. Repeated observations were necessary to demonstrate these differences, and we do not believe that this test is suitable for routine screening for cancer susceptibility.