AIDS, Africa, and academics.
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Biomedical subjects
Publications and source records attributed to A Klopper.
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Biochemical tests of fetal well-being are falling into disfavour. Difficulties arise because we are unable to ascribe specific functions to most test substances, and because they have a large normal range. Nevertheless, a critical survey of the evidence suggests biochemical tests have a part to play in antenatal monitoring, albeit a much reduced one. The main test substances are steroids and proteins produced by the trophoblast. These two classes of substances have a quite different metabolism and compartmental distribution, and the appropriate application of assays is different. A variety of progestogens and oestrogens are used as test substances, the most notable being oestriol. In view of their rapid metabolism, steroid assays serve best in pathological conditions of rapid onset. A dynamic test of the conversion of dehydroepiandrosterone to oestradiol has not fulfilled its initial promise. Among the placental proteins, human placental lactogen is most favoured, although some of the newly discovered proteins may have special applications in certain diseases. The use of biochemical tests in early pregnancy has not been sufficiently explored. The test substances may, in early pregnancy, play a more important role in fetal development and biochemical tests, particularly as a screening test to detect patients at risk of later overt disease, may be valuable.
In a prospective study of 52 patients with ovarian malignancy followed up for 3-18 months the clinical significance of pre-operative serum CA 125 as a tumour marker was assessed. In 41 patients with epithelial ovarian cancer, the level of CA 125 correlated well with tumour load as indicated by FIGO stage. All epithelial histological types, including mucinous, released CA 125 although serous and undifferentiated tumours produced quantitatively more antigen. There was, however, no correlation between CA 125 concentration and histopathological grade, nor did CA 125 level appear to be of any prognostic value in epithelial ovarian cancer. Elevated CA 125 levels were also found in patients with sex cord/stromal tumours. Krukenberg tumours, an ovarian sarcoma and a serous carcinoma of low malignant potential.
PAPP-A, SP1, hCG and alpha 2-PAG were determined in the serum of 17 patients at weekly intervals between 3 and 12 weeks from the last menstrual period; progesterone and 17 beta-oestradiol concentrations were also measured in the same samples. SP1 and hCG concentrations were consistently found to rise steeply from the first time the proteins were detected. PAPP-A, though detectable in early samples from 9 of the patients, started to rise sharply in all cases between 6 and 10 weeks after LMP. Alpha 2-PAG, which was detected in all serum samples, showed no consistent behaviour with advancing pregnancy. In 3 patients, alpha 2-PAG was elevated as early as 3 weeks after LMP, while in others it remained at low levels during the entire interval observed. The correlation between these proteins (except between SP1 and hCG) is therefore poor; and their synthesis or secretion seems to be independently controlled.
The date of delivery in 62 normal pregnant women was predicted by last menstrual period, by ultrasound scan and by the serum concentration of Schwangerschaftsprotein 1 (SP1). It was found that SP1 concentration in the first trimester gave as reliable an indication of when labour would occur as did the last menstrual period or ultrasound scan.
Schwangerschaftsprotein 1 (SP1) values in serum and urine were compared. The first appearance of the protein in urine happens 9-17 days after the first SP1-positive serum, i.e., about 9 days after the first missed period. Urinary SP1 values up to 6 weeks after LMP do not correlate with gestational age as do serum values, but towards the end of the first trimester this correlation becomes almost as good as the one obtained with serum. The urinary SP1 concentration of SP1 fluctuates around 2.3% of the serum concentration throughout pregnancy.
The alpha and the beta forms of Schwangerschaftsprotein 1 (SP1) and chorionic gonadotrophin (hCG) were measured after delivery in an abdominal pregnancy with the placenta left in situ. All three proteins declined more slowly than after normal delivery; the half-lives ranging from 6.2-6.5 days. Traces of the proteins could still be detected in the maternal circulation 9 weeks after delivery. These findings are construed as further support for the belief that the placenta plays a major role in the synthesis of these proteins.
Chorionic gonadotrophin (hCG) and Schwangerschaftsprotein 1 (SP1) were measured in 35 menstrual cycles in 20 women. During the follicular phase, 3 samples were positive for hCG and two of these were also positive for SP1. All these positives occurred on the day of ovulation or immediately before. In the luteal phase 25 specimens showed both hCG and SP1 and two showed only SP1, the positive results occurring 3-15 days after ovulation. The placental proteins were also measured in a further eight women who became pregnant. The pattern in these was quite different. The first positives were detected 8 days after ovulation and by 12 days all the subjects were positive for both proteins. Thereafter both proteins increased sharply in concentration. A group of 139 subjects who, on biological grounds, could not have conceived, showed no positive results.
Daily measurements of serum oestradiol, progesterone, Schwangerschaftsprotein 1 (SP1) and hCG were made in 13 menstrual cycles during which conception occurred. The assays were continued until 21 d after ovulation. SP1 was detected in maternal blood 8-14 d after ovulation and hCG 9-13 d after ovulation. We conclude that these two proteins are secreted simultaneously but independently by the syncytiotrophoblast.
Placental proteins such as human chorionic gonadotrophin (hCG), Schwangerschaftsprotein 1 (SP1) and pregnancy-associated plasma protein A (PAPP-A) are found in the blood of pregnant women and in subjects suffering from cancer. They can also be found in the blood of healthy non-pregnant women and in the seminal fluid of males. Surprisingly, hCG and SP1 could not be found in male serum, although PAPP-A occasionally occurs there.
Serial assays of pregnancy-associated plasma protein A were done in 12 subjects before the first missed menstrual period through 10 to 16 weeks' gestation. It was found that the concentration of pregnancy-associated plasma protein A remained at prepregnancy levels until 6 to 10 weeks after the last menstrual period. Thereafter the concentration increased rapidly. It is surmised that pregnancy-associated plasma protein A is a maternal protein, the synthesis of which is stimulated by pregnancy.
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Assays of SP1 and of hCG were done in three successive menstrual cycles in a woman undergoing artificial insemination from a donor. The day of ovulation was determined by basal body temperature, and by assays of oestradiol and progesterone. In the first cycle no placental proteins were detected, in the second cycle there was a transient peak of SP1 and hCG 4 days after ovulation. In the third cycle both proteins were first detected 12 days after ovulation, then increased rapidly in concentration and the patient went on to a normal pregnancy.
Serial assays of Schwangerschaftsprotein 1 (SP1), SP1 alpha, SP1 beta and human chorionic gonadotrophin were performed in 12 subjects from ovulation until the pregnancies had reached 16 weeks. From these data formulae were devised for deducing the stage of gestation from the concentration of the placental protein. These formulae were then tested by assays on 34 women not included in the original study. Assays of hCG do not give reliable indications of the stage of gestation when this has progressed beyond 9-10 weeks but SP1 assays give predictions of gestation corresponding closely to that derived from the last menstrual period up to 16 weeks gestation.
Pregnancy-associated plasma protein A (PAPP-A) was measured throughout the menstrual cycle in eight women at daily intervals. The protein could be detected in all serum samples, and one patient showed consistently high PAPP-A values during the entire observation period. Twenty-six more women were tested by measuring a single serum specimen. No further high PAPP-A levels were discovered in these. There is no significant difference in PAPP-A concentration between the follicular and the luteal phase of the cycle.
A newly developed enzyme immunoassay technique was applied to the measurement of pregnancy-associated plasma protein A (PAPP-A) in the serum of women in the proliferative and luteal phases of the cycle, in hysterectomized and postmenopausal women and in the serum and seminal plasma of males. PAPP-A was detected in some individuals in all the categories of women and in seminal plasma but not in male serum. It is surmised that there must be a source of PAPP-A other than the placenta and that PAPP-A may be a maternal protein whose biosynthesis is stimulated by pregnancy rather than a product peculiar to the trophoblast.
Pregnancy-associated plasma protein A (PAPP-A) was measured in 26 women before and after hysterectomy. The PAPP-A concentration declined significantly in 24 of them. It is concluded that the uterus is a source of the protein.