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S K Smith

Publications and source records attributed to S K Smith.

At least 145 records · Page 8Linked to original sources
PubMed1994

Estimating temporary populations.

The difficulty of tracking temporary short-term population movements (commuting, seasonal visitation, convention and business travel) is examined, with a focus on Hawaiian statistician Robert Schmitt's work. The author finds that "Schmitt's contributions toward a methodology for estimating daytime populations were important because this approach utilized data sources that were widely available for small areas on at least an annual basis. Consequently, this approach could be used for frequent updates of the estimates, for many areas and at relatively little cost.... The major drawback of the approach is the lack of solid data on temporary residents to serve as larger-area control totals and as a historical base for small-area estimates." The geographical focus is on the United States, particularly Hawaii.

Americas↗
PubMed1993

Alternatively spliced mRNAs for human endothelin-2 and their tissue distribution.

The cDNA for Endothelin-2 (ET-2) has been previously cloned and characterised; however, ET-2 remains the least studied of the endothelin isopeptides and little is known of its function and location. In the present study reverse transcriptase-polymerase chain reaction revealed the presence of seven alternatively spliced mRNA variants encoding ET-2, with a specific pattern of distribution in various human tissues. Computer alignment and analysis of the DNA sequences demonstrated alternative splicing of five exons of 52, 169, 123, 99 and 174 base pairs, in the carboxy terminal region of the mRNA encoding preproET-2. This region contains sites for the post-transcriptional processing of preproET-2 into mature ET-2, therefore we postulate that post-transcriptional processing may be disrupted or altered in these variants.

Alternative Splicing↗
PubMed1993

Properties of large-conductance K+ channels in human myometrium during pregnancy and labour.

The conversion of the electrically silent pregnant uterus to highly excitable at term represents a dramatic physiological event which is poorly understood. Here we provide the first description, from single-channel recordings, of a large conductance (212 pS) calcium-activated potassium channel (BKCa) in human pregnant myometrium which, in labour tissue, is either absent or has been considerably altered in its physiological and pharmacological properties. In the latter, the K+ channels have an identical conductance (221 pS) and K+ selectivity to BKCa channels but exhibit no Ca2+ or voltage sensitivity. We have termed these BK channels. Furthermore, the activity of the BKCa channel from pregnant tissue is inhibited by internal application of Ba2+ but not tetraethylammonium (TEA), whereas the activity of the BK channel is sensitive to internal TEA but not Ba2+. The role of the BKCa channel may be to suppress myometrial activity during gestation whereas BK channel activity may be important in providing a Ca(2+)-independent K+ conductance which would allow cytoplasmic Ca2+ levels to rise without activating a counteracting Ca(2+)-dependent outward current, normally provided by the BKCa channels which, by its very nature, would tend to oppose depolarization. The findings suggest that K+ channels may have an important role in determining the functional activity of the myometrium.

Adenosine Triphosphate↗
PubMed1993

The effects of potassium channel openers on isolated pregnant human myometrium before and after the onset of labor: potential for tocolysis.

OBJECTIVE: Our purpose was to investigate the effects and pharmacologic properties of potassium channel openers in isolated pregnant human myometrium. STUDY DESIGN: Biopsy specimens of myometrium obtained from 67 women during pregnancy and labor were used for isometric recording under physiologic conditions. RESULTS: Levcromakalim and pinacidil, two prototype potassium channel openers, are potent inhibitors of spontaneous and induced (0.5 nmol/L oxytocin and 10 mumol/L phenylephrine) contractions in isolated human pregnant myometrium, obtained before and after the onset of labor. The sulfonylurea glibenclamide is an apparent competitive antagonist of this inhibition. No antagonism was observed with the sulfonylurea tolbutamide. Both potassium channel openers significantly inhibited contractility evoked by low (10 and 20 mmol/L) but not high (40 and 80 mmol/L) concentrations of extracellular potassium chloride. CONCLUSION: These findings suggest that the relaxant ability of levcromakalim and pinacidil in human pregnant myometrium is because of potassium channel activation. This introduces a potential new approach for tocolysis.

Benzopyrans↗
PubMed1993

Evaluation of aspects of the protection afforded to sheep immunised with a gut membrane protein of Haemonchus contortus.

Experiments were undertaken to evaluate the type of protection conferred against Haemonchus contortus by immunising sheep with H11, a 'hidden' integral gut membrane protein isolated from this parasite. A serial kill experiment showed that worms began to be lost from immunised lambs between seven and 14 days after challenge with a single dose of larvae and adult female worms were more susceptible than male worms. Seven-day-old juveniles survived immunisation even though their intestinal cells became coated with sheep antibody. Immunisation was equally effective against both benzimidazole-resistant and susceptible strains of H contortus. When immunised lambs were subjected to a trickle infection, they were largely protected against the anaemia and egg output observed in the challenge controls. Moreover, they grew as fast and as efficiently as uninfected lambs fed on the same high protein diet and acquired a natural immunity during the course of the trickle infection.

Animals↗
PubMed1993

Immunohistochemical localization of acidic and basic fibroblast growth factors in normal human endometrium and endometriosis and the detection of their mRNA by polymerase chain reaction.

Growth factors play a role in the cyclical growth and vascularization of normal endometrium. Abnormal endometrial proliferation and neovascularization may result in endometriosis. This study determines the presence and localization of acidic and basic fibroblast growth factors (aFGF and bFGF respectively) in endometrium of normal women, and in normal and ectopic endometrium of women with endometriosis. Endometrium was obtained at curettage or hysterectomy for benign disease, or laparoscopy for endometriosis. aFGF- and bFGF-immunoreactivity was detected at different phases of the menstrual cycle by immunohistochemistry using primary polyclonal rabbit antibodies. Expression of mRNA for aFGF and bFGF was determined in normal endometrium by nested reverse transcriptase polymerase chain reaction (RT-PCR). aFGF- and bFGF-immunoreactivity were both detected in endometrium from normal women, and in normal and ectopic endometrium of women with endometriosis. The pattern of staining with the two different FGFs was the same: immunoreactivity was predominantly confined to glandular epithelial cells and did not change throughout the menstrual cycle. Little or only light staining was seen in stromal cells and myometrium, and the pattern of staining did not differ between endometriotic and normal tissue. The presence of mRNA for aFGF and bFGF was demonstrated in normal endometrium. The detection of aFGF and bFGF mRNA in normal endometrium and aFGF- and bFGF-immunoreactivity in normal and endometriotic tissues suggests that these peptides may play a role in the proliferation and angiogenesis of normal and ectopic human endometrium.

Base Sequence↗
PubMed1993

Identification and localization of alternately spliced mRNAs for vascular endothelial growth factor in human uterus and estrogen regulation in endometrial carcinoma cell lines.

Repair of human endometrium after menstruation and preparation of the endometrium for implantation involves profound angiogenic changes. Vascular endothelial cell growth factor (VEGF) is a recently identified growth factor with significant angiogenic properties. Four species of mRNA encoding VEGFs were identified in human endometrium and myometrium. All species were present throughout the menstrual cycle. Two species, VEGF165 and VEGF121, were present in peripheral leukocytes, indicating tissue-specific splicing of the two other VEGF transcripts. In situ hybridization of mRNA encoding VEGF was not restricted to vascular smooth muscle but was present in epithelial and stromal cells of endometrium throughout the cycle, and the distribution changed during the course of the cycle. All four species of VEGF were expressed by the endometrial carcinoma cell lines Ishikawa, HEC 1-A, and HEC 1-B. Estradiol increased steady-state levels of mRNA encoding VEGF in a dose- and time-dependent manner in HEC 1-A cells. Conditioned medium from these cells possessed angiogenic activity that was depleted by passage through a heparin affinity column. None of the cell lines demonstrated mRNA for acidic or basic fibroblast growth factor (FGF), despite previous reports of the identification of immunoreactive basic FGF in HEC 1-A and HEC 1-B cells. These findings show that VEGFs, not FGFs, are the principal angiogenic growth factors secreted by these cells and that human endometrium expresses a secreted angiogenic growth factor whose site of expression changes during the menstrual cycle.

Adenocarcinoma↗
PubMed1993

Endothelin-2 mRNA splice variants detected by RT-PCR in cultured human vascular smooth muscle and endothelial cells.

Our aim was to examine the hypothesis that vascular smooth-muscle cells (VSMCs) express only ETA mRNA and endothelial cells express only ETB mRNA and to determine which ET mRNA isoforms are expressed in these cell cultures. Using the reverse transcriptase polymerase chain reaction, we were able to detect ETB, ET-1 and splice variant ET-2 mRNA in cultured human umbilical vein endothelial cells (HUVECs) and ETA and splice variant ET-2 mRNA in cultured aortic smooth-muscle cells. The presence of ET-2 mRNA in cultured VSMCs has not been previously reported. These results agree with the hypothesis that ET-1 may be released from vascular endothelial cells to act predominantly on ETA receptors on VSMCs to stimulate contraction of the underlying smooth-muscle cells, and that endothelium-derived relaxing factor release may be mediated predominantly via the ETB receptors on HUVECs. The role of ET-2 expression from HUVECs and VSMCs is less clear.

Base Sequence↗
PubMed1993

Expression of mRNA for vascular endothelial growth factor in human placenta.

Implantation and growth of the placenta requires extensive angiogenesis to establish the vascular structures involved in exchange. Failure to establish adequate blood supply to the fetus may have serious clinical consequences such as intrauterine growth retardation. Vascular endothelial cell growth factor (VEGF) is a recently identified growth factor with significant angiogenic properties. We have demonstrated the presence of four species of mRNA encoding VEGF in both first trimester and term placenta. In situ hybridization was used to localize the sites of expression of VEGF mRNA in these tissues. VEGF expression was seen in villous trophoblast in the first trimester and in extravillous trophoblast at term, and in both fetal macrophages within the villi and maternal macrophages in the decidua. Glandular epithelium in maternal decidua also expressed VEGF mRNA. The strongest site of expression was in maternal macrophages adjacent to Nitabuch's stria, a zone of necrosis at the site of implantation. This complex pattern of expression suggests that VEGF is involved in angiogenesis on both maternal and fetal sides of the placenta and that macrophages are the primary source of VEGF. However, VEGF may also play a role in term placenta, when extensive angiogenesis has diminished, possibly regulating vascular permeability.

Base Sequence↗
PubMed1992

Platelet-activating factor stimulates phospholipase C activity in human endometrium.

Human preimplantation embryos secrete platelet-activating factor (PAF), which stimulates prostaglandin E2 synthesis from secretory endometrium. This study investigated the action of PAF on phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2)-specific phospholipase C activity in human endometrium. Slices of normal endometrium were incubated with 5 microCi/ml myo-[2-3H] inositol for 3 h at 37 degrees C in 95% O2 and 5% CO2 to label tissue phosphoinositides. Inositol phosphates were extracted using trichloroacetic acid precipitation and diethylether neutralization and production was measured using Dowex 1-X8 anion-exchange column chromatography. PAF induced rapid and concentration-dependent accumulation of inositol phosphates (IP) from secretory endometrium, but had no effect on endometrium removed in the proliferative phase of the menstrual cycle. The IP3 fraction was significantly elevated from a median value of 14.0 c.p.m. mg-1 dry wt [range: 8-41 c.p.m. mg-1 dry wt] to 28.0 c.p.m. mg-1 dry wt [range: 11-87 c.p.m. mg-1 dry wt, P less than 0.002] following 1 min exposure of secretory endometrium to PAF-acether, in the presence of 10 mM LiCl. PAF-induced hydrolysis of PtdIns(4,5)P2 was inhibited by the specific PAF receptor antagonist WEB 2086, in a dose-dependent manner (P less than 0.02), indicating that in human endometrium PtdIns(4,5)P2 hydrolysis is mediated via a PAF receptor. These results indicate that PAF receptor coupling activates endometrial PtdIns(4,5)P2-specific phospholipase C only in the secretory phase of the menstrual cycle, suggesting that the PAF response may be under ovarian steroid regulation. It is proposed that the ability of the endometrium to respond to PAF appears to be a feature of the preparation of this tissue for implantation and that the second messengers generated may play a role in cellular processes involved in the maternal recognition of very early human pregnancy.

Adult↗
PubMed1992

Eicosanoid synthesis and Helicobacter pylori associated gastritis: increase in leukotriene C4 generation associated with H. pylori colonization.

The importance of pro-inflammatory leukotriene C4 in Helicobacter pylori (H. pylori) associated gastritis in man is unknown. Fresh gastric biopsy specimens from 28 dyspeptic patients were obtained: 10 showed normal antral histology with no evidence of H. pylori, the remaining 18 patients exhibited histological gastritis and were H. pylori positive as assessed by histology, culture and urease test. Twelve of these 18 patients received 240 mg twice daily colloidal bismuth subcitrate for four weeks before re-endoscopy. Gastric biopsies from H. pylori positive patients were incubated under basal and Ca(2+)-ionophore mediated conditions: Radioimmunoassay analysis of the supernatant showed basal release of prostaglandin E2 and leukotriene C4 was slightly but not significantly elevated in H. pylori positive mucosa. However in H. pylori positive mucosa there was an 85% increase in leukotriene C4 synthesis when biopsies were incubated with ionophore, compared to only 13% increase in H. pylori negative mucosa (p less than 0.02). After eradication of H. pylori by colloidal bismuth subcitrate, there was a clearance of inflammatory cell infiltrate as assessed by histology and a significant reduction in ionophore-mediated leukotriene C4 formation compared with before treatment (p less than 0.02). These results suggest that H. pylori gastritis is associated with increased capacity to generate leukotriene C4, which may amplify the damaging effects of the bacteria on gastric mucosa.

Adult↗
PubMed1992

The effect of progesterone and human interferon alpha-2 on the release of PGF2 alpha and PGE from epithelial cells of human proliferative endometrium.

Progesterone and interferon-like trophoblastic proteins modulate prostaglandin (PG) synthesis from endometrium in early ovine and bovine pregnancy. Enriched epithelial cells were prepared from human endometrium removed in the proliferative phase of menstrual cycle (n = 8). Progesterone at a concentration of 1 microM suppressed PGE release from the cells during the first 24 hours in culture. After 48 hours in culture progesterone at a dose of 100 nM and 1 microM suppressed both the release of PGF2 alpha and PGE from the cells and this suppression was maintained for a further two days. Addition of exogenous 30 microM arachidonic acid (AA) abolished this effect of progesterone on both PGF2 alpha and PGE release. Interferon alpha-2 did not suppress the basal release of PGF2 alpha nor PGE. In the presence of progesterone, interferon alpha-2 attenuated the progesterone mediated suppression of PGF2 alpha but not PGE release from endometrial cells. These findings suggest that progesterone suppresses the basal release of PGs from human endometrium, but unlike the sheep, interferon alpha-2 does not exert this action on human endometrium.

Arachidonic Acid↗
PubMed1992

Evaluating the forecast accuracy and bias of alternative population projections for states.

"A common perception among producers (and users) of population projections is that complex and/or sophisticated techniques produce more accurate forecasts than simple and/or naive techniques. In this paper we test the validity of that perception by evaluating the forecast accuracy and bias of eight commonly used projection techniques drawn from...four categories [trend extrapolation, ratio extrapolation, cohort-component, and structural]. Using data for [U.S.] state population projections from a number of different time periods, we find no evidence that complex and/or sophisticated techniques produce more accurate or less biased forecasts than simple, naive techniques."

Americas↗
PubMed1992

How changes in components of growth affect the population aging of states.

We analyzed the demographic determinants of population aging for states of the United States between 1950 and 1980. Using the factorial projections method, we estimated the effects of population momentum and changes in mortality, fertility, and migration on changes in the proportion of persons age 65+. Declining mortality rates caused the population to age in virtually every state in every decade between 1950 and 1980, but the effects were very small. The effects of changes in fertility rates were considerably greater. Population momentum generally had a greater effect on population aging than changes in either fertility or mortality rates. Net migration was by far the most volatile component of population aging, both in terms of changes over time and state-to-state differences at a given point in time. We expect this trend to continue in coming decades.

Aged↗
PubMed1992

Platelet-activating factor mediates phosphatidylcholine hydrolysis by phospholipase D in human endometrium.

Human preimplantation embryos and endometrium secrete platelet-activating factor (PAF). The mechanism of phosphatidylcholine (PC) degradation stimulated by PAF was investigated in endometrial explants prelabeled with [methyl-3H]choline or preincubated with [3H]butan-1-ol. Analysis of the water-soluble metabolites of PAF-induced PC hydrolysis in secretory endometrium demonstrated that the stimulated generation of [3H]choline ([3H]Cho) precedes that of [3H]choline phosphate ([3H]ChoP) and [3H]glycerophosphocholine ([3H]GPC). Within 30 sec there was a rapid rise in PAF-induced [3H]Cho generation and by 2 min this had increased to 59.9% +/- 10.6% (p less than 0.02), with no effect upon [3H]ChoP and [3H]GPC during this period. Both [3H]GPC and [3H]ChoP, however, were increased at a later time point. The slower [3H]ChoP generation may suggest that PC-specific phospholipase C activation as well as delayed [3H]GPC rise may be due to PC-specific phospholipase A2 and lysophospholipase activation. Phospholipase D activity was confirmed by the incorporation of high-specific-activity [3H]butan-1-ol into [3H]phosphatidylbutanol ([3H]PBut). The rapid generation of [3H]PBut, which paralleled the rise in intracellular [3H]Cho, strongly suggests that PC breakdown is catalyzed by the phospholipase D pathway. It is proposed that PAF induces PC hydrolysis as a consequence of an early phospholipase D-catalyzed breakdown of PC in human secretory endometrium. This may be an alternative source for prostaglandin synthesis and an important pathway essential for long-term activation of local cellular events at the time of implantation.

Choline↗
PubMed1992

Long-acting gonadotrophin releasing hormone agonist implant causes variable duration of suppression of ovarian steroid and inhibin secretion.

OBJECTIVE: The duration of action of a gonadotrophin releasing hormone (GnRH) agonist implant designed to be effective for 3 months was investigated in women by monitoring drug release and ovarian hormone secretion. Serum inhibin secretion was measured to determine whether the secondary rise in serum FSH concentrations observed during long-term GnRH agonist treatment was attributable to changes in inhibin secretion. DESIGN AND PATIENTS: The implants of slowly biodegradable polylactide/glycolide (molar ratio 75:25) containing 3.3 mg buserelin, D-Ser (But)6-GnRH (1-9)-nonapeptide-ethylamide, in a rod 1 cm long and 0.13 cm diameter were injected s.c. in patients with endometriosis (3.3 mg buserelin in four patients, 6.6 mg buserelin in six patients). MEASUREMENTS: Urinary secretion of oestrone, pregnanediol, LH and buserelin were determined in daily samples collected for 2 cycles before treatment, during treatment, and for 2 recovery cycles. Oestradiol, progesterone, inhibin, LH and FSH were measured in serum collected once per week. RESULTS: In all patients ovarian hormone secretion was suppressed successfully but considerable variability occurred in the length of time taken for ovarian function to recommence, time to return to ovulation being 100-194 days (median 118 days) (3.3 mg group) and 79-290 (median 178 days) (6.6 mg group). After implant injection, there was a rapid rise in the urinary buserelin excretion followed by an early fast phase of buserelin release, half life (t1/2) = 9 days for 3.3 mg implant and 11 days for 6.6 mg implant. This was followed by a second phase representing a plateau of release, t1/2 = 50 days (3.3 mg implant) and 90 days (6.6 mg implant). During this second phase, an excretion rate of greater than 0.2 nmol buserelin/mol Cr was associated with oestrone excretion at or below early follicular phase values. Once buserelin excretion fell below 0.1 nmol/mol Cr, ovarian function returned in all patients. The period for which buserelin secretion was maintained between 0.1 and 0.2 nmol/mol Cr corresponded to the time taken to recovery of ovulatory cycles in 8/10 of the women. In 9/10 patients serum immunoreactive inhibin concentrations declined at 2 weeks, along with the suppression of oestradiol, and remained suppressed throughout the period of anovulation. Recovery of FSH secretion began after 4-5 weeks. CONCLUSIONS: While this implant should have important clinical application where chronic treatment is indicated, further work is needed on design of long-term implants so that such preparations can be used when precise return to ovarian activity is required. A fall in inhibin secretion may contribute to the secondary rise in FSH by withdrawal of negative feedback but these events are not closely correlated.

Adult↗