摘要:

ABSTRACTThe effects of fetal acidosis (mean pH 6.93) on fetal and maternal blood coagulation were measured. Test results from 10 fetal lambs and mother ewes (127 ± 2 days mean gestation) before and after fetal lactic acid infusions were compared to test results from eight control fetal lambs and mother ewes (127 ± 3 days mean gestation) before and after control glucose infusion. Significant changes found in acidotic fetal lambs not seen in control fetuses included an increase in the white blood cell count (mean 2800/mm3 before to 3600/mm3after acidosis;p= 0.0009), a shortening of the thrombin time (mean 17.8 s before to 11.2 s after acidosis;p= 0.0001), and decreases in the activities of factor V (mean 57% before to 37% after acidosis;p= 0.0014) and factor IX (mean 35% before to 29% after acidosis;/) = 0.0128). There was also a reduction in the concentration of fibrinogen (mean 147 mg/100 ml before to 125 mg/100 ml after acidosis;p= 0.0492) but no significant changes in the levels of fibrin monomer, fibrinogen/fibrin degradation products, or antithrombin III. In vitro exposure of five different fetal whole blood samples to a pH of 6.9 for 2 h at 37°C did not result in significant changes in any of the coagulation factor activities. A significant decrease in the level of factor V was also found in the mother ewes of the acidotic fetuses (mean 141% before to 113% after acidosis; p = 0.006) and a decrease in the level of maternal factor IX approached significance (mean 119% before to 102% after acidosis;p= 0.0564). Two hours of severe fetal lactic acidosis induces changes in blood coagulation, but not the usual findings of disseminated intravascular coagulation. Corresponding decreases in factor Y and IX activities in the mothers of acidotic fetal lambs suggest the liberation of a mediator capable of crossing the placenta and influencing maternal coagulation.

ISSN:0031-3998    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

ABSTRACTSerum concentrations of follicle-stimulating hormone, luteinizing hormone, testosterone, and estradiol were determined at intervals before and during puberty in 40 individuals with Klinefelter syndrome (47,XXY karyotype), of whom 27 had been detected in neonatal cytogenetic screening programs. Prior to the appearance of secondary sexual changes, basal serum hormone concentrations and acute responses to stimulation with gonadotropinreleasing hormone and human chorionic gonadotropin were normal. The timing of the onset of clinical puberty was normal. Early pubertal boys showed initial testicular growth and normal serum testosterone levels, while serum follicle-stimulating hormone and estradiol concentrations were significantly elevated. By midpuberty, the Klinefelter subjects were uniformly hypergonadotropic and their testicular growth had ceased. Serum testosterone concentrations after age 15 remained in the low-normal adult range. Serum estradiol levels remained high, irrespective of the presence or absence of gynecomastia. Exaggerated responses to gonadotropin-releasing hormone are seen in pubertal subjects with elevated basal gonadotropin values.

ISSN:0031-3998    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

ABSTRACTTwo infants with disorders of propionate metabolism were studied at 7 months of age to determine optimum levels of intake of protein and calories to meet the requirements for essential amino acid for growth in infancy, and at the same time minimize the accumulation of toxic intermediates. An effect of alanine was found that permitted growth at otherwise limiting levels of protein intake. This was not simply an effect of nonessential nitrogen as neither glycine nor glutamic acid could substitute for alanine in this protein-sparing effect. This appears to represent further evidence of the relationship between alanine and the branched-chain amino acids and of the importance of the alanine-glucose cycle in human physiology.

ISSN:0031-3998    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

ABSTRACTPlasma levels of 17 amino acids were measured in 10 conscious mothers and their minimally stressed fetuses (mean body weight 302 g) at 18-21 wk gestation. Simultaneous blood samples were taken from the maternal antecubital vein, and from the fetal umbilical vein and artery by fetoscopy prior to termination of pregnancy. The mean concentrations of all amino acids were significantly higher in the fetal (2.26 mmol/liter) than in the maternal (0.96 mmol/liter) circulation, the total molar concentration of amino acids was 2.4 times greater in fetal than in maternal plasma. There was a significant positive relationship between maternal and fetal levels for most amino acids; the mean umbilical concentration difference was significantly positive for glycine, alanine, isoleucine, leucine, phenylalanine, and histidine.

ISSN:0031-3998    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

ABSTRACTWe studied the effect of tin protoporphyrin, a potent inhibitor of heme oxygenase (EC 1.14.99.3), on carbon monoxide (CO) production in mature mice. Measurements of CO production provide a sensitive, noninvasive means of quantitating heme catabolism. CO accumulation in the gas space of closed chambers was decreased by about 25% for mice treated with two 50 nmol/g doses of tin protoporphyrin as compared to saline-treated controls. Calculated rates of CO production were 0.28 ± 0.07 and 0.40 ± 0.05 nmol-g-1h-1for mice injected with tin protoporphyrin and saline, respectively (p< 0.01). When hemin (125 nmol/g) was administered to simulate hemolysis, CO production increased markedly in both saline- and tin protoporphyrin-treated mice. However, the rate of CO production in tin protoporphyrin-treated mice was only 44% that of saline-treated animals (p< 0.0001). These studies demonstrate that tin protoporphyrin inhibits heme catabolism in both the basal- and heme-loaded states and confirm that this inhibition is at the heme oxygenase step in the heme to bilirubin pathway.

ISSN:0031-3998    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

We studied the postnatal development of hepatic bile acid conjugation in the rat. Overall conjugating activity (homogenate assay) and the activity of the individual enzymes involved in the two step conjugation reaction (coenzyme A-bile acid thioester formation by microsomal cholyl-CoA ligase and amino acid transfer to this intermediate mediated by cytosolic cholyl-CoA:taurine N-acyltransferase were measured on days 1, 7, 14, 21, and 56 of life. Cholic acid conjugation was significantly lower in the suckling rat on days 1, 7, and 14 compared to the adult rat on day 56. At weaning (21 days) there was a marked increase in homogenate activity to a level higher than at 56 days. This peak in conjugating activity could be precociously induced on day 14 by cortisone acetate injection on days 10 through 13. Both cholyl-CoA ligase and cholyl- CoA:taurine N-acyltransferase activities were significantly lower during the first 14 days of life in comparison with 56 days. At 21 days of age there was a sharp increase in cholyl-CoA ligase activity to 1.5 times the activity in the adult; however, cholyl-CoA:taurine N-acyltransferase activity remained less than half of that found in the adult. We conclude that 1) cholic acid conjugation, as assessed by determination of either total conjugating activity or by the individual enzymatic steps, is decreased in the suckling rat; 2) the peak in conjugating activity noted at weaning may be mediated by the hormonal milieu, and 3) cholyl- CoA ligase activity closely parallels the increase in total activity and appears to be rate-limiting during development.

ISSN:0031-3998    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

The mechanisms underlying the teratogenic effects of alcohol are unknown, and may reflect metabolic differences between adult and fetal tissues. The liver is the major site of alcohol metabolism and the sole site of 25 hydroxyvitamin D synthesis. We have compared 25-hydroxyvitamin D production in adult nonpregnant, maternal, and pup livers obtained from vitamin D-deficient animals and examined the effects of alcohol ingestion on hepatic vitamin D metabolism. 25 Hydroxyvitamin D production was comparable in adult nonpregnant and maternal livers, but was decreased in pup livers compared to their maternal controls (1.4 ± 0.2 versus 0.6 ± 0.1 pmol/g protein/h,p< 0.001). Alcohol ingestion for 18 days had no effect on hepatic synthesis of 25 hydroxyvitamin D in the adult livers, but inhibited production by the pup livers (0.6 ± 0.1versus0.3 ± 0.1 pmol/g protein/h,p< 0.02). To assess the physiologic significance of these observations, the effect of alcohol on 25-hydroxyvitamin D levels in vitamin D-replete mothers and fetuses was determined. Alcohol had no effect on circulating 25 hydroxyvitamin D levels in the mothers but lowered fetal 25 hydroxyvitamin D content (2.3 ± 0.3versus1.2 ± 0.3 ng/g fetus,p< 0.02) without altering fetal weight. The data indicate that differences exist in pup and adult hepatic metabolism of vitamin D and that alcohol has inhibitory effects on pup liver function not expressed in adult tissues.

ISSN:0031-3998    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

9 was rarely present. Thus, the physiological significance of this common abnormality in CF patients with malabsorption remains to be determined.

ISSN:0031-3998    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Hepatic glutamate dehydrogenase (GDH) activity was measured in postmortem specimens obtained from two stage V Reye syndrome patients and in three postmortem specimens of normal human liver. The Reye syndrome specimens showed the hepatic mitochondrial enzyme deficits in GDH and monoamine oxidase activities that are characteristic of Reye syndrome. GDH activity was linear with the amount of supernatant fraction added, both for Reye and normal liver preparations: moreover, the activities of mixtures of Reye and control supernatant fractions were the sums of the activities of the individual components. This means that the activity difference between Reye and normal GDH activity is not due to a diffusible inhibitor in the Reye hepatocytes or to an activator of GDH in the normal control hepatocytes. Serum obtained from six Reye cases during neurologic deterioration was added to normal hepatic GDH preparations to test for a serum inhibitor of FDH. Highly variable effects were found, with two serum samples producing marked inhibition and others showing weak inhibition, no effect, or stimulation of GDH activity. The inhibitor was not removed by charcoal treatment and most of the activity was retained by a 10,000 dalton Diaflo membrane, signifying either that the compound had a high molecular weight or that it was bound to serum protein. We conclude that the decreased activity of GDH in Reye hepatocytes is not due to an intracellular diffusible inhibitor, and that serum effects are quite variable and are not directly related to intracellular changes in GDH activity.

ISSN:0031-3998    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Information about the site(s) of action as well as the age-dependent effects of sex steroids on gonadotropin- releasing hormone and gonadotropin secretion during human puberty is limited. To begin to address these questions, we evaluated the effects of a depot preparation of testosterone (testosterone enanthate) on gonadotropin secretion and pituitary responses to synthetic GnRH in 10,early to mid-pubertal boys who had either isolated GH deficiency (n-2) or delayed adolescent maturation (n-8). Chronological and bone age ranges were 13 1/12—16 1/12 and 11-14 yr, respectively. Frequent blood withdrawal studies (every 20 min for 20 consecutive h) were performed in the Clinical Research Center over two consecutive weekends. Following each study, gonadotropin responses to GnRH (0.25 µg/kg iv bolus) were determined. During the initial study, all boys showed a sleep-entrained increase in luteinizing hormone (LH) and testosterone (T) secretion; mean nocturnal concentrations of LH and T were 2.3-fold greater than daytime values. At the end of the first study, testosterone enanthate was given im (0, 25, 50, or 75 mg/m2). Six days later, mean plasma T concentrations were in the pubertal to mid adult male range and were constant throughout the day: 25 mg/mm2, 3.7 ± 0.4 (SE) ng/ml; 50 mg/m2, 4.6 ± 0.2 ng/ml; and 75 mg/mm2, 6.7 ± 0.4 ng/ml. T treatment had no effect on pituitary responses to GnRH: mean LH increment was 8.5 mlU/ml before and 10.0 mlU/ ml after T treatment. Plasma LH and follicle-stimulating hormone were dramatically suppressed by T; paired analyses, however, revealed the persistence of slightly greater LH values during sleep in four of the nine treated boys. During the control study, LH pulse frequency averaged 2.8 ± 0.3 pulses/6 h during the day and 3.8 ± 0.3 pulses/6 h during sleep. In boys who received 50 or 75 mg/mm2of testosterone enanthate, gonadotropin secretion was profoundly suppressed and LH pulse frequency could not be accurately assessed. However, LH pulse frequency in three boys treated with 25 mg/mm2was not different than their control values: control day, 2.6 ± 0.6; control night, 4.1 ± 0.6; treatment day, 2.1 ± 0.5; and treatment night, 3.9 ± 0.3 pulses/6 h. These results imply that reduction of GnRH secretion is the principal feedback mechanism of testicular steroids in pubertal boys.

ISSN:0031-3998    

出版商:OVID    

年代:1985

数据来源: OVID