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Biomedical subjects

L J Sant-Cassia

Publications and source records attributed to L J Sant-Cassia.

7 recordsLinked to original sources
PubMed1999

The integration of HPV-18 DNA in cervical carcinoma.

AIMS: Little information is available on the patterns of integration into the host chromosomal DNA of cervical carcinomas of human papillomavirus type 18 (HPV-18) DNA, which is associated with up to 20% of these carcinomas. Because integration of the viral genome may be extremely important in the pathogenesis of cervical carcinoma, the aim of this study was to investigate which regions of HPV-18 DNA are integrated into the cellular DNA of cervical carcinomas. METHODS: Southern analysis using four subgenomic probes covering the entire HPV-18 genome was used to map viral DNA integrated within cellular DNA. The polymerase chain reaction (PCR) was used to confirm the presence of specific regions of the viral genome. RESULTS: In all 11 carcinomas there was a single major HPV-18 DNA integrant, retaining approximately 4000 bp of HPV-18 DNA, indicating that approximately half of the virus genome had been lost upon integration. Southern analysis suggested strongly that the viral breakpoint was within the E1/E2 gene boundary, with concomitant loss of part or all of the E2 ORF (open reading frame), all of the E4, E5, and L2 ORFs and part of the L1 ORF. These data were supported by the PCR results, which confirmed that the region of integrated HPV-18 DNA from nucleotides 6558 to 162 was present in all the carcinoma samples studied. Assuming that no genomic rearrangements, deletions, or insertions had occurred, 4131 bp of integrated HPV-18 DNA could be accounted for in eight cervical carcinoma samples. The results of Southern analysis also suggested that integration of HPV-18 DNA may have occurred at a specific host chromosomal site. CONCLUSIONS: Broadly, the viral sequences retained upon HPV-18 integration resemble those found when HPV-16 is integrated. However, it appears that the HPV-18 E2 region is more consistently deleted.

Adult↗
PubMed1984

Midtrimester amniocentesis: is it safe? A single centre controlled prospective study of 517 consecutive amniocenteses.

The outcome of pregnancy following amniocentesis was studied prospectively in 517 consecutive patients undergoing amniocentesis in a single centre. The outcome in 289 of these pregnancies was compared with that in 289 control patients strictly matched for social class, age and parity. There were no significant differences in fetal loss, perinatal mortality or vaginal bleeding between the amniocentesis and control groups. There were significantly more congenital abnormalities in the amniocentesis group (P less than 0.01). These appear to be associated with the amniocentesis procedure and not with the occurrence of raised maternal serum alpha-fetoprotein levels. Although there was an increased risk of preterm delivery (P less than 0.02) there was no significant difference in the distribution of birthweights by centiles for gestational age between amniocentesis and control groups. There was a significant association between intrauterine growth retardation and raised serum alpha-fetoprotein (P less than 0.005). It is concluded that where the indications are strong, amniocentesis continues to be justified.

Abortion, Spontaneous↗
PubMed1983

Nuclear progesterone uptake by endometrial tissue in cases of subfertility.

To investigate the ability of steroid hormones to interact with endometrium, particularly in cases of unexplained subfertility, intact cells were incubated with tritiated progesterone and oestradiol and their uptake into the nuclei was measured. Samples were taken at dilatation and curettage from 23 fertile women, 14 women with unexplained primary subfertility, and 9 patients whose primary subfertility could be explained. Serum oestradiol and progesterone levels were not significantly different between the three groups, nor were values of 3H-oestradiol uptake. However, low (below 5 pmol/mg DNA) values for nuclear 3H-progesterone uptake were present in most samples from women with unexplained subfertility but in only about half of the women in the other two groups. This biochemical defect may be the cause of some cases of unexplained subfertility.

Cell Nucleus↗
PubMed1983

Effects on the renin-angiotensin system of the administration of prostaglandin E1 and E2 in second trimester human pregnancy.

We have measured evoked changes in plasma renin concentration (PRC), plasma renin substrate (PRS) amd plasma aldosterone concentration (ALD) during the infusion of angiotensin II (AII) with and without the simultaneous administration of prostaglandin E2, 5 micrograms min-1 i.v. (PGE2) or prostaglandin E1, 15 ng kg-1 min-1 (PGE1). Experiments have been carried out using PGE2 in 20 patients, and in 5 patients to date with PGE1. AII alone (16 ng kg-1 min-1 i.v.) significantly reduced PRC in both groups of patients without altering PRS, while ALD concentrations more than doubled. The infusion of PGE2 stimulated basal PRC; PGE1 at the dose used did not alter PRC. Neither prostaglandin altered basal RS or ALD concentrations. When AII was infused simultaneously, PRC was again suppressed, in the presence of PGE2. However, only minimal feedback suppression occurred when PGE1 was being used. Furthermore, AII was still associated with a more than two-fold rise in ALD concentration when given together with PGE2, but the rise was considerably smaller and not significant in the presence of PGE1. PGE2 is a known stimulus to renin secretion, apparently acting directly at the juxtaglomerular apparatus. These preliminary results suggest that while a similar mechanism exists in second trimester human pregnancy, PGE1 may have a different effect. The apparent blockade of the normal feedback suppression of PRC in the presence of increased PGE1 concentrations by raised concentrations of AII is especially interesting.

Adult↗
PubMed1981

Chromosomal analysis of couples with repeated spontaneous abortions.

Chromosome banding studies were carried out on both partners of 182 consecutive couples with a history of two or more spontaneous abortions. Seventeen abnormal karyotypes were detected. This represents a frequency of 4.67 per cent, which is higher than hitherto reported. The pregnancy outcome in 105 couples with normal and abnormal karyotype was compared and no significant difference was found.

Abortion, Habitual↗