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Biomedical subjects

S K Smith

Publications and source records attributed to S K Smith.

At least 217 records · Page 12Linked to original sources

The short luteal phase and infertility.

The distribution of the length of the luteal phase was investigated in 187 women with regular, apparently ovulatory menstrual cycles of whom 95 had unexplained infertility and the other 92 comprised a group of healthy volunteer subjects. If the short luteal phase is associated with infertility it might be expected to occur more frequently in women with unexplained infertility. A short luteal phase (defined as a luteal phase lasting less than or equal to 11 days) was found in 9% of the infertile group and in 8% of the normal group showing that these cycles do not occur more frequently in women with infertility.

Female↗

Evaluation of the Pneumoslide latex agglutination test for identification of Streptococcus pneumoniae.

The Pneumoslide latex agglutination tests was evaluated with 106 strains of Streptococcus pneumoniae and 56 strains representing seven species of viridans streptococci. The Pneumoslide test gave one false-positive and one false-negative reaction. Testing of isolated colonies for solubility in 10% sodium deoxycholate was as accurate but was simpler and less expensive to perform.

Deoxycholic Acid↗

Effect of enucleation of the corpus luteum at different stages of the luteal phase of the human menstrual cycle on subsequent follicular development.

To investigate the mechanism of suppression of follicular development during the luteal phase of the human menstrual cycle, the corpus luteum was enucleated surgically from 10 women at various times after ovulation. In the 24 h after CL enucleation there was an immediate and rapid fall in the concentration of oestradiol and progesterone and a temporary decline in the concentration of FSH and LH. Within 3 days, however, all 10 women showed evidence of renewed follicular activity as indicated by a progressive rise in the concentration of oestradiol. This rise was preceded by a rise in the concentration of FSH and LH, and ovulation, as indicated by a mid-cycle surge in LH and rise in the concentration of plasma progesterone, occurred 16-19 days after enucleation. There was no significant difference in the time to ovulation following enucleation at different times of the luteal phase. The post-operative follicular phase, measured from the time of enucleation, was 3 days longer than that observed pre-operatively from the first day of menstrual bleeding. In the follicular phase of post-operative cycles the concentration of FSH was higher and that of oestradiol lower than the corresponding values before surgery. These results indicate that the absence of healthy antral follicles in the luteal phase of the cycle is due to the inhibitory effects of the corpus luteum. The fact that, after CL enucleation, emergence of the dominant follicle was always preceded by a rise in the concentration of FSH and LH suggests that suppression of gonadotrophins by ovarian steroids secreted by the corpus luteum is responsible for the inhibition of follicular development during the luteal phase of the cycle.

Adult↗

Some new techniques for applying the housing unit method of local population estimation: further evidence.

The housing unit method of population estimation is often characterized as being imprecise and having an upward bias. In an earlier paper we argued that the method itself cannot be properly characterized by a particular level of precision or direction of bias. Only specific techniques of applying the method can have such characteristics. In that paper we presented several new techniques for estimating the number of households and average number of persons per household (PPH). However, the testing of these new techniques was limited by the lack of census results against which the estimates could be compared. Complete census data on population, households, and PPH are now available and can be used to test alternate estimation techniques. In this paper we replicate the tests reported in our earlier paper using 1980 census data for Florida's 67 counties. These tests provide further evidence that the new techniques produce more precise, less biased estimates than previously used techniques.

Demography↗

Premenstrual levels of 17 beta oestradiol and progesterone in plasma in cycles of short and normal luteal phase length.

Premenstrual levels of 17 beta oestradiol and progesterone in plasma were compared between cycles of short or normal luteal phase length. Levels of progesterone and 17 beta oestradiol were higher premenstrually in cycles with short luteal phase lengths (11 or less days) that in cycles of normal luteal phase length (12 or more days). These findings suggest that reduction in the length of the luteal phase may arise because of a changed response of endometrium to withdrawal of 17 beta oestradiol and progesterone.

Adult↗

Evidence that human platelet alpha-adrenergic receptors coupled to inhibition of adenylate cyclase are not associated with the subunit of adenylate cyclase ADP-ribosylated by cholera toxin.

Exposure of the alpha-adrenergic receptor of the human platelet to agonist prior to solubilization stabilizes a receptor complex of the alpha-adrenergic receptor with the GTP-binding protein(s) which modulates receptor affinity for agonists (Smith, S. K., and Limbird, L. E. (1981) Proc. Natl. Acad. Sci. U. S. A. 78, 4026-4030). The soluble alpha-adrenergic receptor is characterized by retention of sensitivity to GTP and a faster rate of sedimentation in sucrose gradients than antagonist-occupied or unoccupied receptors. The present studies were undertaken to determine whether the alpha-adrenergic receptor, which is coupled to inhibition of adenylate cyclase, contains the same GTP-binding protein that is involved in activation of adenylate cyclase. The GTP-binding protein that is coupled to activation of adenylate cyclase was labeled with [32P]ADP-ribose using cholera toxin. Incorporation of [32]ADP-ribose into a Mr = 42,000 peptide in human platelet membranes was paralleled by an enhancement of GTP-sensitive catalytic activity in the membranes. However, cholera toxin treatment did not modify alpha-receptor-mediated inhibition of adenylate cyclase or interaction of the alpha-receptor with agonist agents. Moreover, sucrose gradient centrifugation revealed that the [32P]ADP-ribosylated Mr = 42,000 subunit of the stimulatory GTP-binding protein did not appear to associate with the agonist-alpha-receptor complex. These data suggest that the GTP-binding protein that mediates GTP activation of adenylate cyclase in the human platelet membrane is distinct from the GTP-binding protein that modulates alpha-adrenergic receptor affinity for agonist agents and which associates with the receptor in the presence of agonists.

Adenosine Diphosphate Ribose↗

Hormonal regulation of beta-adrenergic receptors in fetal rabbit lung in organ culture.

Explants of fetal rabbit lung were established on the 25th day of gestation. These were maintained in serum-free medium for periods up to 10 days. During this time, the cultures exhibited morphological changes typical of terminal lung differentiation. Morphological evidence was also obtained for synthesis and secretion of pulmonary surfactant in these explants. beta-Adrenergic receptors were identified in these lung explants. Exposure of the explants to 10(-7)M dexamethasone on the third day of culture resulted in a significant increase in the number of beta-adrenergic receptors in the tissue without a change in receptor affinity. The effect of dexamethasone in organ culture was dose-dependent, a maximum increase in receptor number being observed within 48 hours of incubation with a hormone concentration of 1 x 10(-7)M. Exposure of the explant tissue to 1 x 10(-7)M triiodothyronine resulted in no significant increase in the concentration of beta-adrenergic receptors and no change in receptor affinity. These results suggest that glucocorticoids may potentiate the effects of beta-adrenergic agents in the fetal lung by increasing the numbers of their receptors. The effects of triiodothyronine upon the fetal lung do not appear to be mediated by this mechanism.

Animals↗

Androgen receptors in fetal rabbit lung and the effect of fetal sex on the levels of circulating hormones and pulmonary hormone receptors.

High affinity (KD = 0.2 nM), low capacity (3.6-5.0 fmol/mg protein), androgen-specific binding proteins with characteristics typical of androgen receptors were identified in the lungs of rabbit fetuses between the 26 and 29th day of gestation and in the lungs of adult rabbits. While androgen receptor concentrations increased significantly from late gestation to adulthood (P less than 0.01), no sex-related differences were observed in either the binding affinities or concentrations of the receptors at any age tested. Similarly, no sex-related differences were found in the levels of progesterone, cortisol and cortisone in the fetal circulation, or in the levels of progesterone receptors, glucocorticoid receptors and beta-adrenergic receptors in the fetal lung at 26 days of gestation. It is concluded that the fetal lung interacts directly with circulating androgens via specific androgen receptors and that the suggested male disadvantage with respect to lung maturation in the perinatal period does not appear to be associated with sex-related differences in the levels of pulmonary androgen, glucocorticoid, progesterone or beta-adrenergic receptors.

Animals↗

The synthesis of prostaglandins from persistent proliferative endometrium.

The pattern of prostaglandins (PGs) synthesized by persistent proliferative endometrium of women with excessive menstrual bleeding (greater than 50 ml) associated with anovulatory cycles was compared to endometrium collected from women with normal menstrual blood loss (less than 50 ml). Levels of PGF2 alpha in normal and persistent proliferative endometrium were lower than the levels of PGF2 alpha found in normal secretory endometrium (P less than 0.005 for both normal and persistent proliferative endometria). When incubated with exogenous [1-14C]arachidonic acid (9.1 nmol), normal secretory endometrium synthesized more PGF2 alpha and PGE2 than did normal proliferative endometrium, but the amounts of PGF2 alpha and PGE2 released by persistent proliferative endometrium were similar to those obtained by normal secretory endometrium. These findings suggest that persistent proliferative and normal secretory endometria have the same PG synthetase activity, and that the low endogenous concentrations of PGF2 alpha in the former arise from a lack of endogenous precursor. PGF2 alpha has predominantly vasoconstricting properties, and a reduced capacity to synthesize this PG by persistent proliferative endometrium may result in excessive menstrual bleeding, as was suggested by the inverse correlation between the ratio of the endogenous concentrations of PGF2 alpha and PGE and the menstrual blood loss (r = -0.7; P less than 0.005; n = 26).

Adult↗

A role for prostacyclin (PGi2) in excessive menstrual bleeding.

The synthesis of prostanoids from arachidonic acid incubated with endometrium alone or together with myometrium was studied in women with excessive menstrual blood-loss (range 57--186 ml, median 86 ml). Production of prostaglandins F2 alpha, E2, and D2 was similar to that observed for the endometrium of women with normal periods (range 5--50 ml; median 11 ml). However, the endometrium from women with excessive menstrual blood-loss was more effective than endometrium from women with normal menstrual blood-loss at enhancing the production by a control preparation of myometrium of 6-oxo-prostaglandin F1 alpha, the stable metabolite of prostacyclin. The ability of the uterus to generate prostacyclin, a prostaglandin known to inhibit platelet aggregation and stimulate vasodilatation, may influence the degree and duration of menstrual bleeding.

6-Ketoprostaglandin F1 alpha↗

Solubilization of human platelet alpha-adrenergic receptors: evidence that agonist occupancy of the receptor stabilizes receptor--effector interactions.

The alpha-adrenergic receptors of human platelet membranes can be directly identified by both a radiolabeled agonist, [3H]epinephrine, and a radiolabeled antagonist, [3H]yohimbine. Digitonin solubilizes a binding component from the membrane that is indistinguishable from the alpha-receptor identified in the native platelet membrane as assessed by (i) order of potency of agonists and antagonists and (ii) affinity of the receptor for [3H]-yohimbine and competing antagonists. However, the solubilized receptor demonstrates a reduced affinity for agonists and a loss of the ability of guanine nucleotides to modulate receptor affinity for agonists. Prelabeling of human platelet membranes with [3H]-epinephrine results in a guanine nucleotide-sensitive agonist-receptor complex that sediments more rapidly in sucrose gradients than do unoccupied or antagonist-occupied receptors. Thus, agonist occupancy of the alpha-receptor prior to membrane solubilization may promote or stabilize receptor interaction with effector components in the membrane, one of which may be the GTP regulatory protein responsible for modulation of receptor affinity.

Blood Platelets↗

Prostaglandin synthesis in the endometrium of women with ovular dysfunctional uterine bleeding.

The endogenous concentrations of prostaglandins F2 alpha (PGF 2 alpha) and E (PGE) were measured during the luteal phase of the menstrual cycle in the endometrium from 14 women with unexplained menorrhagia (measured menstrual blood loss in excess of 50 ml) and 15 women with normal menses (blood loss 50 ml or less). Although there was no significant difference in the PGF 2 alpha/PGE ratio between the two groups, this ratio was significantly lower in the endometrium from eight of the women whose blood loss exceeded 90 ml (p less than 0.05). There was a significant inverse correlation between the PGF 2 alpha/PGE ratio and blood loss (r = 0.36, p less than 0.025). The synthetic capacity of the endometrium was assessed by incubation of the tissue with 14C arachidonic acid. Endometria from nine women with unexplained menorrhagia synthesized more PGE2 than PGF 2 alpha, whereas the converse was true with 11 control endometria. Consequently the PGF2 alpha/PGE2 ratio was significantly reduced in the former group (p less than 0.025). Oestradiol-17 beta (200 microM) and to a greater extent 2 hydroxy oestradiol (200 microM) increased the total prostaglandin synthesis by the endometria, but did not significantly alter the PGF2 alpha/PGE2 ratio. These results suggest that excessive blood loss may be associated with a shift in the endometrial conversion of prostaglandin endoperoxide from PGF2 alpha to PGE2.

Adolescent↗

The use of 16-16 dimethyl trans delta 2 PGE1 methyl ester (ONO 802) vaginal suppositories for the termination of early pregnancy. A comparative study.

Vaginal suppositories containing the 16-16 dimethyl trans delta 2 PGE1 methyl ester (ONO 802) were used for the induction of abortion in early pregnancy, and this non-surgical technique was compared with suction termination performed under local anaesthesia or general anaesthesia. Ninety patients were recruited to the study and divided equally between the three groups. Complete abortion was induced in 87 per cent of the patients treated with ONO 802 suppositories, which compared favourably with 87 and 100 per cent for the patients who had suction terminations under local anaesthesia and general anaesthesia respectively. The vaginal suppositories induced uterine bleeding in all patients and the mean time of onset of lower abdominal pain was 2 hours 55 minutes. The average numbers of episodes of vomiting and diarrhoea for patients given ONO 802 suppositories were 0.9 and 0.7 respectively. Menstrual blood loss was measured objectively in all groups and no significant differences between the three methods could be found. In selected cases, ONO 802 vaginal suppositories would seem to be safe and reasonably effective for the termination of early pregnancy.

16,16-Dimethylprostaglandin E2↗

Suppression of concentration of endometrial prostaglandin in early intra-uterine and ectopic pregnancy in women.

Concentrations of prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E (PGE) were measured in endometrium from 18 women with ectopic pregnancies. In the nine pregnancies not associated with vaginal bleeding or an intra-uterine contraceptive device (IUCD; intact ectopics), concentrations of PGF2 alpha (12.8 +/- 7.4 (S.E.M.) ng/g) and PGE (4.7 +/- 3.0 ng/g) were similar to those in decidua from nine intra-uterine pregnancies of comparable gestational age (14.4 +/- 4.4 and 8.2 +/- 2.2 ng/g respectively). In both ectopic and intra-uterine pregnancies concentrations of prostaglandins were significantly lower than those found in endometrium throughout the normal menstrual cycle (P < 0.01). In nine ectopic pregnancies with associated vaginal bleeding and/or an IUCD, concentrations of PGF2 alpha and PGE were significantly higher than in the intact group (P < 0.05), although the concentration of PGF2 alpha remained significantly lower than levels in normal secretory endometrium (P < 0.05). These results suggested that suppression of endometrial synsthesis of prostaglandin during early pregnancy may be mediated systemically rather than through a local action of the conceptus.

Chorionic Gonadotropin↗

Some new techniques for applying the housing unit method of local population estimation.

The housing unit method of population estimation is often characterized as being imprecise and having an upward bias. We believe that the method itself cannot properly be characterized by a particular level of precision or direction of bias. Only specific techniques of applying the method can have such characteristics. In this paper we discuss several new techniques we have developed for estimating households and the average number of persons per household. Estimates produced by these techniques are compared to estimates produced by several other techniques. Special census results from Florida provide preliminary evidence that the new techniques produce more precise, less biased estimates than the other techniques.

Florida↗