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Studies of the microaerophilic nature of Campylobacter fetus subsp. jejuni. II. Role of exogenous superoxide anions and hydrogen peroxide.

The addition of bovine superoxide dismutase to Brucella broth or Brucellar agar greatly echanced the oxygen tolerance of Campylobacter fetus subsp. jejuni strain H840 (ATCC 29428). Catalase also enhanced oxygen tolerance, but to a lesser extent. These enzymes must act externally to the bacteria. All of the diverse compounds which enhance oxygen tolerance of C. fetus, including nor-epinephrine and a combination of ferrous sulfate, sodium metabisulfite, and sodium pyruvate, share the ability to quench either superoxide anions or hydrogen peroxide. On the basis of these and other data, we propose that C. fetus is more sensitive to exogenous superoxide anions and hydrogen peroxide than are aerotolerant bacteria, despite the occurrence of superoxide dismutase and catalse activities in C. fetus. Compounds that enhance oxygen tolerance in C. fetus appear to act by quenching superoxide anions and hydrogen peroxide which occur spontaneously in the culture medium.

Campylobacter

Reduced hepatic bilirubin uridine diphosphate glucuronyl transferase and uridine diphosphate glucose dehydrogenase activity in the human fetus.

Hepatic bilirubin uridine diphosphate glucuronyl transferase (UDPG-T) activity was 0.14 and 0.22 units in two fetuses aged 17 and 22 weeks, respectively, and less than 0.1 unit in 15 fetuses, aged 8--19 weeks compared to 0.68--1.99 units in 21 normal adults. Hepatic uridine diphosphate glucose dehydrogenase (UDPG-D) activity in 14 fetuses, aged 8--18 weeks, ranged from 6.2--15.0 units (mean = 11.3 +/- 0.7) compared to 28.8--49.2 units (mean = 39.6 +/- 2.5) in eight normal adults (P less than 0.001). There was no correlation between UDPG-D activity and gestational age. The hepatic UDPG-D activity was 16.5 units in a 33-day-old full term, female infant, 42.4 and 24.3 units in two 2-year-old infants, respectively, and 24.3 units in a 5.5-year-old child. In three human fetuses, the apparent Km UDPG was 0.54 x 10(-4) M. Thus, both hepatic bilirubin UDPG-T and UDPG-D activity are markedly reduced in the human fetus during the second trimester of gestation. Retarded development of hepatic UDPG-D may extend beyond the first month of life.

Adult

Temporal changes in activities of enzymes reducing ring-A of progesterone in the fetus and placenta of the rat.

The development of delta4-5alpha-reductase and 3alpha- and 3beta-hydroxysteroid dehydrogenases in rat fetuses and placentas was detected by the production of specific metabolites during in vitro incubation with progesterone. The metabolites, 5alpha-pregnane-3,20-dione, 3alpha-hydroxy-5alpha-pregnan-20-one, and 3beta-hydroxy-5alpha-pregnan-20-one, were identified by isolation and purification by thin-layer chromatography and reverse isotope dilution, followed by recrystallization of the free compound and a derivative. The delta4-5alpha-reductase and the 3beta-hydroxysteroid dehydrogenase are associated with the particulate fraction. However, 3alpha-hydroxysteroid dehydrogenase is a soluble enzyme present in the supernatant fraction of homogenized placentas and fetuses. The activities of these enzymes were greater in the placenta than in the fetus. As pregnancy progresses, the activities increase in the fetus, but diminish in the placenta. Although the placenta secretes only marginal amounts of progesterone, it has a notable capacity to metabolize progesterone to 5alpha-reduced metabolites. The fetus has the ability to utilize progesterone as early as day 13, and its potential to convert progesterone into ring-A reduced products increases during gestation.

Animals

Pituitary hormone levels in plasma of the human fetus after administration of LRH.

The concentrations of hFSH, hLH/hCG, hGH, and hTSH1 were measured in maternal and fetal blood during the second trimester of pregnancy before and after the administration of 10 mug LRH to 9 fetuses. A comparison was performed with 9 control fetuses not receiving LRH. The initial value of hFSH was significantly higher in female than in male fetuses (P less than 0.01) and in both sexes exceeded the low maternal hFSH level. A similar fetomaternal difference existed also for plasma hGH, in contrast to plasma hLH/hCG, which concentration was higher in maternal than in fetal blood LRH did not cause any change of circulating hFSH, hLH/hCG, and hTSH levels in the fetus 10 min after its administration. A rise of fetal hGH levels occurred during the observation time irrespective of LRH administration. In amniotic fluid, the hFSH concentration accorded with that in fetal blood, and the hLH/hCG concentration with that in maternal blood. The fetal plasma levels of these pituitary hormones suggest selective release mechanisms for the various peptides. The causes of the absent response of blood gonadotropin levels to LRH in the fetus are discussed.

Chorionic Gonadotropin

[The effect of androgens upon the differentiation of Cowper and Bartholin glands in rat fetuses (author's transl)].

In the present paper, a study is made of the normal structure shown in Bartholin and Cowper glands of 100 female fetuses and 100 male fetuses of Wistar rats at the end of gestation, with the structure of bulbouretral glands that formed in 70 female fetuses of the same species and period of gestation masculinized by androgens. In relation to the Bartholin glands, whose bilateral sketch is constant in the fetuses, we can affirm that it shows significant differences of structure with regards to the sketch of the Cowper gland. On the opposite, the histologycal details of the latter, are entirely identical to those shown by the bulbouretral glands of the masculinized female fetuses, a fact which permits us to affirm that these are authentic Cowper glands, not only because of their position, but also because of their structure. This morphological data corresponds to a masculinization phenomenon and demonstrates that the Bartholin and Cowper glands are very sensitive to the effect of androgens during gestation.

Animals

[Penetration, distribution and retention of chlortetracycline in the body of pregnant rabbits and their fetuses].

Chlortetracycline was administered to the rabbits per os in a single dose of 150000 Units/kg. After 29-30 days of pregnancy the rabbits were sacrificied 1--3--6--9--12--24-hours and 2--3--4 days after the drug administration. Three-four rabbits were examined in every experiment. The antibiotic levels were determined by the agar-diffusion method. It was found that chlortetracycline was present in bactericidal concentrations in all 60 tissues of the rabbits and fetus examined except the rabbits eye lens. In some tissues of the rabbit and fetus chlortetracycline persisted up to 3 and 2 days respectively. The antibiotic levels in the organs, tissues and fluids of the fetus were many times lower than those in the rabbits. The concentration peak in the fetus was attained somewhat later and the rate of the concentration decrease was lower as compared to the same indices in the rabbit. The highest concentrations of chlortetracycline in the fetus were registered in the amniotic membranes, joints, bones, urine and amniotic fluid.

Animals

Immunocytological localization of LH, FSH, TSH and their subunits in the pituitary of normal and anencephalic human fetuses.

Immunostaining with antisera to oLH, hCG, hLH, pLHbeta, hFSH, hFSHbeta, hTSHalpha and bTSH was used to delineate the gonadotropic and thyrotropic cells of the human fetal anterior pituitary. Hypophyses from 29 normal fetuses, 3 newborn infants, and 5 totally ancencephalic fetuses were used. Several controls to check for the specificty of the immunocytological reaction were made. In normal fetuses, observations showed that: 1) the alpha subunit was detected from the eighth week and throughout gestation without sex differences; 2) intact LH was detected during the third month, however, age and sex differences were observed during the fourth and fifth months; 3) intact FSH was detected in female fetuses from the beginning of the fourth month, a sex difference was observed; 4) LH and FSH were detected in the same cells; 5) the thyrotropic cells were detectable from 15 weeks of gestation and their number increased during gestation without sex difference; 6) at birth the gonadotropic cells were scarce and were located in the ventromedian zone of the anterior pituitary, while the thyrotopic cells remained numerous and were located in the dorsomedian zone. In amencephalic fetuses: 1) the alpha subunit existed at each stage studies; 2) the reaction induced by anti-pLHbeta and anti-hFSHbeta sera was alwys very weak regardless of sex or age; 3) the thyrotropic cells were more numerous in comparison to the gonadotropic cells. These data are discussed in terms of the relationship of the hypophysiotropic hypothalamic factors to the appearance and evolution of the glycoprotein hormones and their subunits.

Anencephaly

Passive transmission of Campylobacter fetus by immunised bulls.

Two groups of 24 heifers were mated with 3 immunised and 3 susceptible bulls respectively. Six heifers in each group were infected artificially with Campylobacter fetus sub-sp. fetus biotype venerealis. Among susceptible heifers mated with immunised bulls, 13/18 became pregnant and 5/18 yielded evidence of infection with C. fetus. Among susceptible heifers mated with susceptible bulls, 7/18 became pregnant and 10/18 yielded evidence of infection. C. fetus was isolated on one occasion from an immunised bull, but the immunised bulls failed to develop carrier status and one was shown to be refractory to artificial challenge. Susceptible bulls developed carrier status during the breeding period. It is suggested that passive transmission of C. fetus by immunised bulls can occur under conditions of intensive sexual activity.

Animals

Daily changes in the curved crown-rump length of individual sheep fetuses during the last 60 days of pregnancy and effects of different levels of maternal nutrition.

A method is described by which daily changes in the curved crown-rump length (CRL) of individual sheep fetuses were observed during the last 50 to 60 days of pregnancy. The mean discrepancy between the derived value for CRL and the CRL measured directly in eight fetuses aged between 100 and 135 days and in 12 lambs born at 143 to 150 days was 1.5 +/- 0.2 per cent (mean +/- s.e.). In adequately nourished ewes between 100 and 115 days of gestation growth rate showed a between-fetus range of 4.2 to 7.5 mm.day-1 (n=16), remained constant within each fetus until about 132 days and then decreased by about 27 per cent (n=4). Decreases in growth rate of about 30 to 44 per cent occurred within three days of the introduction of maternal undernutrition at 115 or 120 days of gestation (n=6) and in two other fetuses maternal undernutrition effected an almost complete cessation of growth. The relationship between fetal CRL and weight is described and some physiological implications of the results are discussed.

Animals

Stimulation of testosterone production in vivo and in vitro in the male rhesus monkey fetus in late gestation.

To assess intrauterine fetal testicular function, the carotid or femoral vessels of rhesus monkey fetuses, 129-145 days gestational age, were catheterized following hysterotomy of the mother. The fetus was returned to the uterus, the catheters were exteriorized through the mother's vagina and the pregnancy was allowed to continue. In this chronic preparation, basal levels of testosterone (measured with an RIA with 65% cross-reactivity with 5 alpha-dihydrotestosterone) in male fetal serum were 0.85 +/- 0.29 (SD) ng/ml. Administration of a 10 or 100 IU intra-arterial bolus of hCG into the fetal circulation stimulated in increase in fetal serum testosterone levels of 70 and 630%, respectively. Other fetuses were challenged with bolus infusions of 10 and 50 micrograms of synthetic gonadotropin releasing hormone (GnRH). The lower dose caused an increase in serum testosterone concentrations in only one of four fetuses, while the higher dose resulted in a positive response in all three experiments performed. With this dose, the mean increase in circulating testosterone concentration after 1 h was 105%. In vitro, specific binding of iodinated hCG was demonstrated in testicular homogenates from rhesus fetuses near term and hCG stimulated testosterone biosynthesis in testicular minces. Maximal stimulation was achieved at hCG concentrations between 5 and 50 ng/ml. The data indicate that the testes of fetal rhesus monkeys during late gestation are capable of androgen biosynthesis and can bind and respond to gonadotropin stimulation. Furthermore, the pituitary-gonadal axis in the fetal male monkey is capable of responding to GnRH stimulation at this stage of gestation.

Animals

Plasma cortisol and cortisone in pregnancies with normal and anencephalic fetuses.

Plasma cortisol (F), cortisone (E), and progesterone (P), were measured in the umbilical vein (UV), umiblical artery (UA), and maternal peripheral vein (MPV) of 17 normal patients, and of 8 patients carying anencephalic fetuses. The plasma F in MPV of patients undergoing vaginal delivery after labor of spontaneous onset was significantly higher than that of patients delivered by elective cesarean section, whereas the plasma F concentrations in the UA or UV of the 2 groups were not statistically different from each other. The anencephalic fetuses had UA plasma F and E concentrations which were significantly lower than those of normal fetuses, suggesting that a main portion of UA cortisol and cortisone originates in the fetal adrenal. The UV and MPV plasma F and E concentrations of patients carrying anencephalic fetuses did not differ, however, from those of normal patients, suggesting that these UV corticoids are derived mainly from maternal sources. The amniotic fluid cortisol levels of the patients carying anencephalic fetuses were lower than those observed in the normal pregnancies, suggesting that amniotic fluid cortisol is derived mainly from fetal sources.

Anencephaly

[The effect of ACTH and chorionic gonadotropin on cyclic 3',5'-adenosine monophosphate concentration and of a homogenate of fetal hypophysis on adrenal steroidogenesis in human embryos and fetuses from the 7th to the 12th week of embryonic development].

It was shown that homogenates of the hypophysis of human fetuses from the 8th to the 12th week of gestation stimulated in vitro formation of F and DEA-sulfate in the adrenal glands of fetuses of the same gestation period. ACTH increased the cAMP concentration in the adrenal glands of all the embryos and fetuses under study; this pointed to the presence in them of ACTH-dependent adenylcyclase, and, consequently, of the ACTH receptors. On the contrary, chorionic hormone produced no effect on the cAMP concentration in the adrenal glands. The data obtained, together with those published earlier suggested that adrenal glands of human fetuses from the 8th week of gestation were already under the controlling influence of ACTH of their hypophyses and that the action mechanism of ACTH on the adrenal glands of fetuses was analogous to its action on the adrenal glands of adult.

Adrenal Glands

Dexamethasone treatment of the guinea pig fetus: its effects on the incorporation of 3H-thymidine into deoxyribonucleic acid.

Pregnant guinea pigs of 50 to 53 days' gestation (term 63 days) were anesthetized with ether, and their fetuses were injected intramuscularly with 30 mg of dexamethasone or sterile saline. One week later, the fetuses were injected with 3H-thymidine intramuscularly under direct vision at laparotomy; after one hour, the incorporation of thymidine into deoxyribonucleic acid (DNA was analyzed in various fetal tissues. The relative labeling of DNA was significantly depressed in the cerebral hemispheres, cerebellum, medulla oblongata, and midbrain of the treated fetuses compared to their littermate controls. The relative labeling of the DNA of lungs, kidneys, heart, and adrenals was also significantly reduced. Increasing the dose of dexamethasone produced a progressive inhibition of the incorporation of 3H-thymidine into DNA. A variable recovery from the inhibition became apparent by 14 days following exposure to dexamethasone. The evidence suggests that exposure of the fetus to dexamethasone may exert a potentially deleterious effect on fetal tissues.

Adrenal Glands

Chemical and biochemical studies in human fetuses affected with Niemann-Pick disease type A.

Chemical and biochemical studies were performed on two unrelated fetuses affected with Niemann-Pick disease type A, following abortion at about the 19th week of gestation. Abortion was performed as a consequence of previous findings, in amniotic fluid cell cultures, that sphingomyelinase activity was completely absent. Phospholipid analyses of various organs of the fetuses revealed an excess of sphingomyelin in all viscera as compared to control nonaffected fetuses. Spleen and liver were the organs mostly affected. Interestingly enough considerable accumulation of sphingomyelin was found in the placenta. The brain was the only organ in which sphingomyelin storage could not be proved. In addition to sphingomyelin a slight accumulation of cholesterol was noticed. Deficiency of sphingomyelinase activity measured at pH 5.0 was the general characteristics of the affected tissues. It could be concluded that the accumulation of sphingomyelin in various organs throughout the body of fetuses affected with Niemann-Pick disease, was suggestive of the essential role of the enzyme sphingomyelinase and its biochemical maturation, even during the early stages of gestation.

Brain

Genital mycoplasma infection. Intrauterine infection: pathologic study of the fetus and placenta.

Mycoplasma infection was present in the fetuses from three spontaneous abortions and in one second-trimester newborn. Gross examination revealed in most cases a severely infected placenta and membranes, with a fetus of normal appearance. The fetal infection presumably followed placental involvement and appeared to have been acquired shortly prior to delivery. Genital mycoplasmas, Ureaplasma urealyticum or Mycoplasma hominis, were isolated from the placentas and the fetal tissues, and from the genital tracts of the mothers. Isolation of mycoplasmas from the liver indicated that bloodstream dissemination of these organisms occurred in the fetus. In the fetus, the pathologic changes were variable. Lesions were identified in the lung by scanning electron microscopy of the bronchial tree in two cases and were accompanied by interstitial pneumonia. An abnormally dilated left ventricle suggestive of cardiomyopathy was observed in one case.

Adult

alpha-Fetoprotein levels in pregnancies complicated by gastrointestinal abnormalities of the fetus.

alpha-Fetoprotein (AFP) levels have been measured in maternal serum and amniotic fluid in a variety of gastrointestinal abnormalities of the fetus. Maternal serum AFP levels were consistently elevated in abdominal wall defects of the fetus after 15 weeks gestation and the amniotic fluid levels were raised in 3 of the 4 patients measured. In atresia of the gastrointestinal tract and diaphragmatic hernia, serum AFP levels were usually normal unless there was an associated neural tube defect or multiple pregnancy, although the majority were not measured between 15 and 26 weeks gestation. If elevated amniotic fluid levels of AFP are used in the decision to terminate pregnancy on the assumption of a probable neural tube defect of the fetus, a proportion of terminations will be performed because of abdominal wall defects of the fetus.

Abdominal Muscles

Development of cardiovascular responses to sympathomimetic amines and autonomic blockage in the unanesthetized fetus.

The cardiovascular effects of phenylephrine or ephedrine alone and after autonomic blockade was studied in the chronically cannulated fetal lamb (100-145 days), the newborn lamb, and adult sheep. As gestation advanced, phenylephrine and ephedrine produced an increasing pressor response before and after pretreatment with atropine (1 mg/kg). Compared with the fetus, the magnitudes of the pressor responses were somewhat greater in the newborn and much larger in the adult. Both drugs produced a reflex bradycardia in the unatropinized fetus which in the case of ephedrine was followed by a tachycardia. Pretreatment with atropine resulted in an immediate tachycardia after ephedrine but not after phenylephrine administration. Pretreatment with phentolamine (0.15 mg/kg) produced about a 55% inhibition of the phenylephrine pressor response in both the fetus and adult, suggesting a linear relationship between body weight and number of alpha-adrenergic receptors. Pretreatment with metoprolol blocked the tachycardia associated with ephedrine administration to unatropinized fetuses. In summary, the increase in the magnitude of the pressor response to phenylephrine suggested development of the receptor-effector system. The greater development of the response to ephedrine suggested that there was an increasing amount of noradrenaline being released with advancing gestation.

Animals

Dynamics of glucose-induced plasma insulin increase in the rat fetus at different stages of gestation. Effects of maternal hypothermia and fetal decapitation.

The effect of glucose on the release of insulin from the pancreas of 19.5- to 21.5-day-old rat fetuses has been studied in utero. Fetal hyperglycemia was induced by a square-wave glucose infusion into pregnant rats over a period of 150 min. The infusion of glucose raised the fetal blood glucose concentration to that of the mother and induced a rapid increase of plasma insulin levels on day 19.5 of gestation. There was a progressive rise of the insulin response as the gestation proceeded, with an increase of the two phases of the hormonal secretion. Maternal hypothermia induced by pentobarbital anesthesia decreased markedly the insulin response to hyperglycemia in the mothers and their fetuses. In fetuses decapitated on day 18.5 and studied on day 21.5, the increase of plasma insulin concentration after a 1-hour hyperglycemia was similar to that in the littermate control fetuses.

Animals