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Biomedical subjects

J A Winter

Publications and source records attributed to J A Winter.

At least 19 recordsLinked to original sources
PubMed1997

Relationship between androstenedione-induced myometrial contractions and platelet-activating factor acetylhydrolase in late gestation in pregnant rhesus monkeys.

An association between platelet-activating factor (PAF) and myometrial contractions has been established. Estrogens regulate PAF activity via reduction in the activity of plasma PAF acetylhydrolase (PAF-AH), the enzyme that catalyzes PAF inactivation. Administration of androstenedione to pregnant monkeys leads to sustained increases in maternal plasma estradiol (E2), with persistent nocturnal myometrial contractions. The present study tested the hypothesis that androstenedione-induced contractions are associated with a fall in maternal plasma PAF-AH activity in monkeys. Eight monkeys (132-136 days gestation, dGA) were instrumented under halothane anesthesia with maternal vascular catheters and uterine electromyogram electrodes. At 138-142 dGA, two baseline maternal arterial samples were taken for E2 and PAF-AH measurements. The following day a continuous i.v. androstenedione infusion was started in 4 monkeys while 4 control monkeys received i.v. infusions of vehicle alone. Arterial blood sampling was repeated 1 and 3 days after the start of either infusion. Despite an increase in maternal E2 to term levels and established myometrial contractions, no change in maternal plasma PAF-AH activity occurred after androstenedione treatment. Maternal plasma E2, PAF-AH activity, and contractions remained unchanged from baseline in control monkeys. In conclusion, androstenedione-induced increases in maternal plasma E2 and myometrial contractions are not associated with a fall in maternal plasma PAF-AH specific activity.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1997

Timing of the switch from myometrial contractures to contractions in late-gestation pregnant rhesus monkeys as recorded by myometrial electromyogram during spontaneous term and androstenedione-induced labor.

Pregnant rhesus monkeys were studied to determine the precise time in relation to photoperiod of the onset, and the nature, of the switch in myometrial activity patterns from contractures to contractions. We investigated both spontaneous term labor and androstenedione-induced preterm labor. Under general anesthesia at 127 +/- 2 days gestation (dGA) (mean +/- SEM), 16 pregnant rhesus monkeys were instrumented with maternal femoral arterial and venous catheters and myometrial electromyogram electrodes. Eight animals (group I) received continuous i.v. infusion of intralipid (n = 7) or saline (n = 1) that was started at 143.3 +/- 2 dGA and maintained until the spontaneous onset of term labor. Nine animals (group II) received continuous i.v. infusion of androstenedione that was started at 139 +/- 0.4 dGA and maintained until the onset of prematurely induced labor. Myometrial activity was recorded continuously. All monkeys in both groups demonstrated nocturnal switches in myometrial activity from contractures to contractions. The mean time of onset of the switch in group I and group II monkeys was similar, occurring at 0.7 +/- 0.4 h or 0.8 +/- 0.5 h, respectively, after the onset of darkness. Group II monkeys demonstrated greater regularity in both the time of onset and the repetitive occurrence each night once the switch occurred, as well as greater consistency in duration in their switch patterns, than did group I monkeys.

Androstenedione↗
PubMed1997

Proteinuric hypertension in a pregnant baboon: was this pre-eclampsia?

We report the results of investigating a pregnant baboon that developed hypertension, proteinuria, and oedema in late gestation. Although the clinical presentation suggested a diagnosis of pre-eclampsia, the evolution of her clinical signs and results of a renal biopsy performed 3 weeks after delivery suggested that glomerulonephritis was the underlying disease.

Aged↗
PubMed1996

Daily and hourly temporal association between delta4-androstenedione-induced preterm myometrial contractions and maternal plasma estradiol and oxytocin concentrations in the 0.8 gestation rhesus monkey.

OBJECTIVE: Our purpose was to investigate the temporal relationship between delta4-androstenedione-induced preterm switching of myometrial activity patterns from contractures to contractions and maternal plasma estradiol and oxytocin concentrations in the 0.8 gestation rhesus monkey. STUDY DESIGN: Eight rhesus monkeys (132 to 136 days' gestation) were instrumented under halothane with femoral artery and vein catheters and uterine electromyogram electrodes. At 138 to 142 days' gestation baseline maternal femoral artery blood samples for estradiol and oxytocin measurement were taken at 30-minute intervals for 7 hours, starting 2 hours before the onset of darkness. The day after baseline sampling a continuous intravenous delta4-androstenedione infusion (0.3 mg . kg-1 .hr-1 in 10% intralipid at 0.25 ml . hr-1) was started in four monkeys, while four monkeys were infused intravenously with intralipid alone. The sampling regimen was then repeated at 1 and 3 days after the start of the delta4-androstenedione or intralipid infusion. Contractions were counted and estradiol and oxytocin were measured by radioimmunoassay. RESULTS: Androstenedione promoted a premature nocturnal increase in myometrial contractions in conjunction with an increase in maternal plasma concentrations of estradiol and oxytocin, which were of similar magnitude to those measured in spontaneous term labor. The increase in maternal estradiol preceded the increase in maternal oxytocin levels and myometrial contractions. The onset of the increase in maternal plasma oxytocin was closely associated with the appearance of myometrial contractions after delta4-androstenedione treatment. In contrast, no sustained premature contractions or changes in estradiol and oxytocin occurred in intralipid-treated monkeys. CONCLUSIONS: We conclude that in the 0.8 gestation rhesus monkey (1) the increase in maternal plasma estradiol precedes the increase in maternal plasma oxytocin after delta4-androstenedione treatment and (2) delta4-androstenedione-induced preterm myometrial contractions are closely associated in time with physiologic increases in maternal plasma oxytocin concentrations.

Analysis of Variance↗
PubMed1996

Effect of androstenedione administration on the maternal hypothalamo-pituitary-adreno-placental axis in the pregnant rhesus monkey.

To assess the interaction among androgens, placenta, and the hypothalamo-pituitary-adrenal axis we studied effects of androstenedione administered intravascularly to the pregnant monkey on maternal plasma CRH, ACTH, dehydroepiandrosterone sulfate (DHEAS), cortisol, and estradiol concentrations. Ten monkeys (128 +/- 3 days gestation; mean +/- SEM) were instrumented under general halothane anesthesia with maternal femoral artery and venous catheters and uterine electromyogram electrodes. At 137-144 days gestation, baseline maternal femoral artery samples for CRH, ACTH, DHEAS, cortisol, and estradiol measurements were taken at 1.5-h intervals for 7 h starting 2 h before darkness. On the following day, a continuous iv androstenedione infusion (0.3 mg/kg.min at 0.25 ml/h) in 10% intralipid was started at 0930 h in four monkeys; the other six animals received vehicle alone at the same rate starting at the same time. Maternal blood sampling was repeated 1 and 3 days after androstenedione or vehicle administration. Maternal plasma CRH, ACTH, DHEAS, cortisol, and estradiol levels were unaffected by intralipid. In contrast, androstenedione infusion produced a sustained increase in maternal plasma estradiol and a sustained fall in maternal plasma ACTH, but did not affect maternal plasma CRH, DHEAS, or cortisol concentrations. These results provide evidence for negative feedback regulation by androgens at the hypothalamo-pituitary-adrenal axis in the pregnant monkey. Lack of inhibition of maternal plasma CRH after androstenedione administration supports differential regulation of hypothalamic and placental CRH by androgens.

Adrenocorticotropic Hormone↗
PubMed1996

The oxytocin antagonist atosiban prevents androstenedione-induced myometrial contractions in the chronically instrumented, pregnant rhesus monkey.

We tested the hypothesis that increased oxytocin is a necessary mechanism for the mediation of androstenedione (delta 4A)-induced myometrial contractions by investigating the effects of maternal treatment with the oxytocin antagonist atosiban on in vivo delta 4A-induced contractions. In four monkeys (group I), maternal estradiol, oxytocin, and myometrial contractions were assessed at baseline and after continuous iv delta 4A administration. Similar measurements were made in three monkeys (group II) that received the same delta 4A infusion regimen, but in addition were treated daily with atosiban. Maternal estradiol and oxytocin levels and contractions were also assessed in four additional monkeys (controls; group III), in which the delta 4A vehicle, intralipid, was infused iv continuously. In group I, delta 4A induced myometrial contractions and increased maternal estradiol and oxytocin to term concentrations. No myometrial contractions occurred in group II monkeys after combined delta 4A and atosiban treatment despite estradiol being elevated to concentrations similar to those measured in group I monkeys. Atosiban had no effect on maternal heart rate or blood pressure. Maternal estradiol, oxytocin, and number of myometrial contractions remained unchanged from baseline values in control monkeys. In conclusion, oxytocin is a necessary part of the mechanisms mediating delta 4A-induced myometrial contractions. delta 4A promotes myometrial contractions via similar mechanisms that mediate spontaneous term contractions in pregnant monkeys.

Androstenedione↗
PubMed1995

Regulation of the switch from myometrial contractures to contractions in late pregnancy: studies in the pregnant sheep and monkey.

Myometrial contractility occurs throughout pregnancy and characteristic patterns of myometrial activity exist according to the endocrine status and the relationship to parturition. These characteristic patterns differ between species, yet certain common features can be observed. Throughout pregnancy, myometrial activity is of the contractures type, long-lasting, low-amplitude epochs of activity switching to contraction-type activity at term. This switch from contractures to contractions tends to occur at night and is related to alteration in maternal plasma oestrogen concentrations, and maternal oxytocin function. Studies in several animal species support the hypothesis that maternal oestrogen prepares the myometrium for a periodic signal that causes the switch from contractures to contractions. Several lines of evidence implicate oxytocin in the switch. These studies show that the detailed preparation for parturition takes longer than previously considered and is brought about by a carefully regulated sequence of events in which oestrogen production by the placenta plays a central role.

Animals↗
PubMed1995

Radiologic manifestations of pulmonary tuberculosis.

In summary, the following points are reemphasized: 1. The chest film is the mainstay in the radiologic evaluation of suspected or proven pulmonary TB. CT is occasionally useful for clarifying confusing findings but has not been conclusively shown to have a significant impact on patient management. 2. Primary TB is increasingly a disease of adults. 3. Primary TB usually manifests as a parenchymal consolidation in any pulmonary lobe or segment. Distinguishing features from typical bacterial pneumonia include associated adenopathy, lack of systemic toxicity, failure to respond to conventional antibacterial therapy, and recent PPD conversion. 4. Associated ipsilateral hilar and/or mediastinal adenopathy is almost universal in children with primary TB but is less common in adults. Adenopathy without parenchymal disease is an unusual but well-reported manifestation. 5. Many of the so-called unusual manifestations of adult TB are the usual manifestations of primary disease. The terms adult and childhood TB should be discarded. 6. Postprimary TB typically manifests as a heterogeneous, often cavitary opacity in the apical and posterior segments of the upper lobes and the superior segments of the lower lobes. Lymphadenopathy is rare. 7. Activity of postprimary disease cannot be accurately assessed by chest radiography. Radiographic stability for 6 months and negative sputum cultures is the best indicator of inactive disease. The descriptive terms inactive or old TB should be discarded in favor of radiographically stable TB, as viable bacilli may persist despite adequate therapy. 8. Cavitation is the most important radiologic finding in postprimary disease. Cavitation implies a high bacillary burden, high infectivity, and is associated with numerous complications including endobronchial spread, tuberculous empyema, hematogenous dissemination, pulmonary artery pseudoaneurysm, and so forth. 9. Tuberculous pleurisy is more common in primary than postprimary disease. It is a common presenting manifestation in young adults. The effusions are unilateral, large, and self-limited. The pleural fluid usually is a serous exudate with a marked lymphocytosis. Fluid cultures are frequently negative. Correct diagnosis and therapy is important, as untreated patients are at high risk for subsequent pulmonary reactivation. 10. Miliary disease is also more common in primary than postprimary disease; however, its frequency in elderly patients with postprimary TB is increasing. This form, known as late generalized TB, is apt to be misdiagnosed or not diagnosed in life and has a high mortality.

Adolescent↗
PubMed1988

Structure, expression, and evolution of the 5-enolpyruvylshikimate-3-phosphate synthase genes of petunia and tomato.

5-Enolpyruvylshikimate-3-phosphate (EPSP) synthase is an enzyme of the shikimate pathway which is located in the chloroplasts in higher plants. This enzyme is the target of the nonselective herbicide glyphosate. We have isolated and sequenced cDNA clones encoding EPSP synthase from petunia and tomato. The deduced amino acid sequences of the two enzyme precursors show 93% identity in the mature protein regions and 58% identity in the transit peptides. The sequences of the plant enzymes show significantly greater similarity to bacterial EPSP synthases than to fungal EPSP synthases. A genomic clone containing an EPSP synthase gene was isolated from a library of petunia DNA and was shown to contain seven intervening sequences. This gene is expressed approximately 25-fold higher in flower petals than in other organs of petunia. Transcription of this gene is initiated at multiple sites in petunia leaves and in a glyphosate-tolerant petunia cell line overproducing EPSP synthase mRNA. In petals, however, transcription of this gene is initiated almost entirely from only one of these sites. In contrast to petunia, the levels of EPSP synthase mRNA in different organs of tomato do not differ significantly.

3-Phosphoshikimate 1-Carboxyvinyltransferase↗
PubMed1987

Comparison of cauliflower mosaic virus 35S and nopaline synthase promoters in transgenic plants.

We have compared the level of expression of the Cauliflower Mosaic Virus 35S promoter and the nopaline synthase promoter when fused to a common reporter gene. A cassette containing the neomycin phosphotransferase (type II) coding sequence followed by the nopaline synthase 3' nontranslated region was used for transcriptional and translational evaluation of the two different promoters. These chimeric genes were introduced into petunia plants and the copy number of the gene, the steady state level of NPTII transcript and the levels of NPTII enzyme activity were determined. In this paper, we report that the NPT II transcript levels are on the average 30 fold higher in plants containing CaMV 35S promoter and leader sequences than in plants containing the same reporter gene but nopaline synthase promoter and leader sequences. Similarly, plants containing the CaMV 35S promoter had an average of 110 fold higher levels of NPTII enzyme activity than those containing the nopaline synthase promoter. The significance of these results for expression of foreign genes in plants is discussed. In addition, we describe the construction of a convenient plant expression cassette vector (pMON316) which utilizes the CaMV 35S promoter.

Amino Acid Oxidoreductases↗
PubMed1984

Map locations of five transcripts homologous to TR-DNA in tobacco and sunflower crown gall tumors.

Polyadenylated RNA from two octopine type tumor lines (E1, PSCG-15955) was analyzed by RNA blot hybridization and shown to contain five major transcripts homologous to TR DNA. In tobacco E1 tissue, the molecular weights of the TR homologous RNAs are 1.65 kb, 1.55 kb, 1.45 kb, 1.05 kb, and 0.78 kb. The 5' - and 3'-termini of each of the five E1 tumor transcripts were determined by S1 nuclease hybrid protection mapping. The polarity of transcription for the 0.78, 1.05 and 1.65 kb RNAs is from left to right, while the 1.55 and 1.45 kb RNAs are transcribed from right to left. Although we see the same size transcripts in sunflower PSCG-15955 tissue (with the exception of a 0.89 kb RNA in place of the 1.55 kb transcript of E1) there is an apparent difference in the relative abundance of the various RNAs between the two tumor lines.

Base Sequence↗
PubMed1983

Concentration of 18:1 and 16:1 transunsaturated fatty acids in the adipose body tissue of decedents dying of ischaemic heart disease compared with controls: analysis by gas liquid chromatography.

Proportions of "lower" 16:1 and 18:1 trans acids (TL) and "higher" C20 and C22 trans acids (TH) in samples of depot fat taken at postmortem examination from 136 people who had died of ischaemic heart disease (cases) and from those who had died of unrelated causes (controls) have been determined. Whereas mean percentages of TH are virtually identical for cases and controls, the mean value of TL was significantly higher for the case specimens. Although these lower trans acids are present in small amounts in ruminant-animal fat, they are more characteristic of commercially hydrogenated fats. We conclude, therefore, that the cases consumed on average a higher proportion of those hydrogenated fats rich in 16:1 trans and 18:1 trans acids and a lower proportion of ruminant fat than did the controls.

Adipose Tissue↗
PubMed1983

Concentration of transunsaturated fatty acids in the adipose body tissue of decedents dying of ischaemic heart disease compared with controls.

The constituents of the fat of 136 decedents who had died of ischaemic heart disease are compared with the constituents of the fat from 95 controls who had died from other causes. The cases had a lower concentration of fatty acids (L) characteristic of ruminant animal fat and a higher concentration of total transunsaturated acids (T), but the concentrations of certain higher (C20 and C22 mostly monoenoic) acids (H) were similar. The ratio T/L was higher in the cases, which suggests that the cases may have consumed more hydrogenated fats in life than had the controls. The ratio T/L increased linearly with H within both the case and control specimens, which suggests in view of the similarity in the mean levels of H that the difference in trans contents may be concentrated in the lower (18:1 and 16:1) trans acids.

Adipose Tissue↗
PubMed1981

Hydrogenated oils and fats: the presence of chemically-modified fatty acids in human adipose tissue.

A total of 231 samples of adipose tissue has been analyzed for trans unsaturated acids which arise in large measure via consumption of hydrogenated fat; 136 specimens derived from patients who had died of ischemic heart disease (cases), the remainder being controls. They have also been analyzed by gas-liquid chromatography which gave information regarding the amounts of 1) "higher acids"--C20 plus C22 acids, mainly monoenoic--which derive from hydrogenated marine oils present in high amounts in certain margarines in the United Kingdom, and 2) "lower acids"--14:1 plus odd-numbered and branched chain acids in the C15 to C17 range--which are present in hydrogenated fat in lower amounts than in, say, butter-fat. Values of trans unsaturated acids tend to be higher, and values of lower acids lower for cases than controls, but we cannot at present conclude that these differences are statistically significant. Case versus control levels in respect of higher acids and linoleic acid do not appear to be significantly different.

Adipose Tissue↗