摘要:

The mechanism of low serotonin content in Down's syndrome (DS) platelets was studied by comparing the activity of (Na+/K+)-ATPase, ouabain binding, and rate of outward movement of sodium in platelets from DS and control subjects.Ouabain inhibited (Na+/K+)-ATPase activity in sodium iodide-extracted platelet membranes from 10 normal subjects had an average value of 2.87 ± 0.20 μmol Pi./hr/109platelets whereas the activity from DS platelet membranes was 2.13 ± 0.19 μmol Pi/hr/109platelets (P< 0.02). Total ATPase activity in normal platelet membranes was 3.58 ± 0.33 μmol Pi/hr/109platelets whereas that from DS membranes was 2.49 ± 0.35 μmol Pi/hr/109platelets (P< 0.02). (Na+/K+)-ATPase activity is decreased in DS platelets.Ouabain binds specifically to (Na+/K+)-ATPase sites on membranes. The amount of ouabain bound by DS platelets is less than that by control platelets. The average amount of ouabain bound was 1.08 ± 0.04 × 10-15mol/109platelets for controls and 0.86 ± 0.02 × 10-15mol/109platelets for DS (P< 0.001). There appear to be fewer (Na+/K+)-ATPase sites on DS platelets compared to normal.The outward movement of Na+in platelets is catalyzed by the enzyme (Na+K+)-ATPase. The average ouabain-sensitive outward movement of sodium in normal platelets was 9.03 ± 0.46 μmol/hr/109platelets. For DS subjects the average outward movement was 50% of normal, 4.41 ± 0.14 /μmol/hr/109platelets. The rate of outward Na+transport is significantly less (P< 0.001) in DS compared to normal platelets.Decreased serotonin content of DS platelets may be secondary to decreased (Na+/K+)-ATPase activity, which results in decreased rate of outward Na+transport and increased Na+content. As serotonin is cotransported with Na+, the decreased rate of serotonin uptake may be secondary to increased Na+content of DS platelets.Speculation If decreased (Na+/K+)-ATPase activity, decreased rate of Na+outward transport, increased Na+content, and decreased rate of serotonin uptake were also present in synaptosomes of DS patients, decrease in amine content might occur and result in altered ncurotransmission.

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

The serum nonesterified fatty acids (NEFA), triglycerides, total cholesterol, lipid P, lysolecithin, sphingomyelin, lecithin, and phos-phatidylethanolamine were determined on 15 full term and 13 premature jaundiced infants, before and after 48 hr of phototherapy and compared to nonjaundiced matched control subjects.The cholesterol levels of the jaundiced full term newborns were significantly higher than those of the healthy control full term infants. Differences were also observed before and after phototherapy between the jaundiced full term and the jaundiced premature infants in the serum lipid P and sphingomyelin values, which were lower in the premature subjects. The serum triglycerides values of the jaundiced full term control infants were lower than those of the nonjaundiced newborns. A significant decrease of serum NEFA was observed after phototherapy in both the full term and premature groups of jaundiced infants.The differences noted in cholesterol and lipid P levels may be due to liver dysfunction because of the jaundice. The differences in NEFA levels before and after phototherapy can be caused by the photooxidative breaking up of the NEFA by the phototherapy, by the decreased absorption of NEFA, or the increased catabolism of lipids. The decreased synthesis of NEFA from ketone bodies and glucose, or the probability of binding of NEFA by the bilirubin during the phototherapy must also be considered.Speculation The higher serum cholesterol levels observed in the jaundiced infants could be due to hepatic damage (dysfunction or excretory impediment).The differences in NEFA levels before and after phototherapy can be caused by the photooxidative breaking up of the NEFA by the phototherapy, by the decreased absorption of NEFA, or by the increased catabolism of lipids. The decreased synthesis of NEFA from ketone bodies and glucose, or the probability of binding of NEFA by the bilirubin during phototherapy must also be considered.

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

Pulmonary function was studied before and after bilateral lung lavage with oxygenated FC-80 fluorocarbon liquid in seven preterm Iambs, 134 days of gestation. Measurements of transpulmonary pressure, air flow, tidal volume, and functional residual capacity (FRC) enabled calculations of lung resistance and compliance, specific compliance, and work of breathing. Immediately postlav-age, arterial oxygen tension (PaO2) decreased significantly (P< 0.05) by 41% from control values. In addition, at 1 hr postlavage, lung compliance significantly decreased (P< 0.01) by 43% from control levels. Lung resistance, FRC, work of breathing, arterial carbon dioxide tension, and pH postlavage were not significantly different from postlavage values. The mean volume of FC-80 remaining in the lungs at 1 hr postlavage was 32% of the instilled volume. These data indicate that lung lavage with a low surface tension liquid has a relatively small effect on lung mechanics of the premature lung.Speculation Adequate blood gas tensions and pH levels can be maintained both during and after bilateral fluorocarbon lavage with relatively small changes in lung mechanics. Based upon these findings, it is appealing to speculate that bilateral fluorocarbon lavage may be useful as a means of alveolar debridement, particularly in aspiration syndromes of the newborn.

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

The amount of radioactivity accumulated in normal skin fibro-blasts cultured in the presence of64Cu increased during the first few hours of incubation, and reached a plateau after 18 hr. Fibroblasts from patients with Menkes syndrome continued to accumulate64Cu and after 48 hr, the mutant cells contained over 3 times more radioactivity than the normal cells. Normal skin fibroblasts grown in the presence of64Cu for 24 hr and chased for 6 and 24 hr with64Cu-free medium released 78% and 91% of the radioactivity, respectively, whereas Menkes fibroblasts grown under similar conditions released only 22% and 51%, respectively. The amount of radioactivity incorporated by fibroblasts increased with increasing concentrations of64Cu in the culture medium, but the Menkes fibroblasts incorporated more64Cu than normal fibroblasts. A slight reduction in the incorporation and efflux of64Cu was seen with several metabolic inhibitors, but there was no difference between normal and mutant cells. Treatment of labeled cells with trypsin did not affect the amount of64Cu picked up by the cells. Most of the radioactive copper incorporated by the cells was not precipitated by trichloroacetic acid or phosphotungstic acid, although the percentage of precipitated64Cu was consistently higher in normal than in Menkes fibroblasts. Most of the64Cu was bound to a molecule with a molecular weight of about 10,000, whereas a small fraction, proportionally higher in normal cells, was bound to a large molecular weight component(s). The amount of64Cu bound to the small molecular weight species was significantly greater in Menkes fibroblasts than in normal cells. Menkes fibroblasts were more sensitive to high nonphysiologic levels of nonradioactive copper than were normal cells. These findings demonstrate pronounced metabolic differences between normal and Menkes fibroblasts and indicate the need for further studies before proper treatment of this disease can be instituted.Speculation Copper picked up by cultured skin fibroblasts is preferentially bound to a molecule with a molecular weight of about 10,000. The increased copper accumulation in Menkes fibroblasts may be caused by the deficiency of an enzyme that catalyzes the cleavage of this bond, by the presence of an increased amount of this small molecular weight molecule in the mutant cells, or by an increased binding capacity of this molecule for copper.

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

Leukocyte preparations from cystic fibrosis (CF) patients produced markedly less adenosinc 3‘:5’-monophosphate (cAMP) in response to isoprotercnol than normal cells. Both stimulation ratio and net isoproterenol-stimulated accumulation of cAMP were significantly (P< 0.001) lower in mixed leukocyte preparations from 20 CF patients (29 trials) compared to 21 normal subjects (49 trials). There was no significant correlation of results with clinical score, and no differences in the CF group attributable to medications or presence of pancreatic insufficiency. CF heterozygotes had mean stimulation ratio and mean net isoproterenol-stimulated cAMP intermediate between normal and CF. There were no statistically significant differences among normal subjects, CF patients, and CF heterozygotes in basal cAMP or prostaglan-din E1-stimulated cAMP. Purified mononuclcar cells from five normal persons and seven CF homozygotes had the same basal and prostaglandin E1-stimulated cAMP, but isoproterenol-stimulated cAMP was markedly depressed (P< 0.01) in the CF cells. Granulocytes from six normal persons and nine CF patients also had the same basal and prostaglandin Ei-stimulated cAMP, but isoproterenol-stimulated cAMP was decreased (P< 0.05) in the CF samples. These results clearly demonstrate a difference between normal and CF leukocytes in cAMP response to β-adrener-gic stimulation.Speculation The diminished cAMP response to β-adrenergic stimulation in CF is probably related to the presence of a CF gene, and may interact with other genetic abnormalities to produce the clinical syndrome of CF.

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

Testosterone concentrations were measured by radioimmunoassay in 57 amniotic fluid samples obtained from 43 women whose gestational ages varied from 14–40 weeks. These women were grouped according to the sex of the fetus and the gestational age at the time of amniocentesis: group I, less than 20 weeks; group II, 21–30 weeks; group III, 31–40 weeks. In each gestational age group, mean testosterone concentrations were significantly higher in women bearing male fetuses. Of the 14 patients comprising group I, 8 bore male fetuses. The mean testosterone concentration for male fetuses in this group was 198.7 pg/ml (range 93–319.8 pg/ml) and 74.1 pg/ml for female fetuses (range 39–122.8 pg/ml). Group II was comprised of 23 patients, 13 of whom bore male fetuses. The mean testosterone concentration for male fetuses was 221.5 pg/ml (range 133.6–395.0 pg/ml), and for female fetuses it was 67.7 pg/ml (range 35.6–103.0 pg/ml). Group III consisted of 20 patients of whom 10 bore male fetuses. The mean testosterone concentration for the male fetuses was 149.1 pg/ml (range 99.2–262.0 pg/ml), and for female fetuses it was 60.2 pg/ml (range 39.5–96.7 pg/ml). Some overlapping of individual testosterone values was observed in fluid from male and female fetuses; however, the percentage of women bearing males and having amniotic fluid testosterone concentrations greater than 100 pg/ml was 93.5% (29/31). The percentage of women bearing females with testosterone concentrations less than 100 pg/ml was 88.5% (23/ 26).Speculation Amniotic fluid testosterone concentrations have proven useful for the antenatal diagnosis of fetal sex. Correlation between the fetal sex based upon testosterone analysis and the amniotic fluid karyotype increases the probability that the cultured cells are of fetal origin. Certainty of diagnosis could be increased even further by combining antenatal sex diagnosis with fluorescent Y-chromatin screening of uncultured amniotic fluid. A combination of these techniques should aid in the elimination of diagnostic errors arising from contamination by maternal cells.

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

Sick low birth weight infants (LBWI) are prone to develop rapid onset of essential fatty acid (EFA) deficiency. EFAs serve as precursors for prostaglandins (PGs). We measured the excretion of the major urinary metabolite of prostaglandins E1and E2, 7α-hydroxy-5, 11-diketotetranorprostane-1, 16-dionic acid (PGE-M), in three EFA-deficient and in nine thriving neonates. There was no significant difference in PGE-M excretion between the sexes among thriving infants nor did PGE-M excretion appear to be affected by postconceptual age. However, a significant difference between the PGE-M excretion in the group of infants with EFA deficiency before and after treatment is apparent (P< 0.05). Significant differences in PGE-M excretion were also found between the control group and the EFA-deficient infants. The severity of the EFA deficiency correlates directly with the degree of PGs excretion. The biochemical evidences of EFA deficiency and the decreased levels of PGE-M excretion are rapidly corrected when patients resume a diet containing EFA.Speculation The decrease in PGE-M excretion in patients with EFA deficiency is most likely related to a decrease in the precursor EFA, although PG synthetase deficiency or altered PG metabolism has not been ruled out. Further investigation is needed into the patho-physiologic consequences of EFA deficiency as well as decreased PG biosynthesis and turnover in the sick low birth weight infant.

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

In order to evaluate the role of surfactant lecithin composition in the development of the infantile respiratory distress syndrome (IRDS) we have examined lecithin fatty acid composition from gastric aspirates obtained at the time of delivery from 14 full term healthy infants, 9 control premature infants without respiratory distress, and 16 premature infants who developed IRDS. The latter had significantly reduced concentrations of palmitic acid (48.4 ± 1.8% vs. 65.3 ± 1.5% in fullterm and 59.5 ± 0.8% in control premature infants,P< 0.001). None of the infants in whom palmitic acid was more than 60% of total lecithin fatty acids developed IRDS, whereas 10 of 11 infants with values below 50% did develop this complication. Lecithin from gastric aspirate was shown to be similar in fatty acid composition to lecithins from tracheal washings and amniotic fluid. Palmitic acid concentrations in lecithins of serial tracheal washings paralleled the clinical course of eight infants with IRDS.Speculation The enzyme systems involved in the biosynthesis of pulmonary surfactant are complex. Failure of maturation of these systems can result in inadequate synthesis of total lecithins or in a selective deficiency of dipalmitoyl lecithin, an essential component of surfactant. Therefore, studies directed to determining the composition of surfactant lecithins may result in better diagnosis, understanding, and management of IRDS.

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

After a single force-feeding of hypertonic (1300 mOsm) mannitol to rats there is rapid osmotic equilibration of the jejunal fluid, a sharp drop in luminal mannitol concentration and large influxes of water and sodium. During osmotic equilibration there was a significant loss of cells from the jejunal mucosa. In hypertoaically fed rats there was an accumulation of protein, DNA, [3H] thymidine-labeled DNA, and disaccharidases in intestinal washings. Brush border disaccharidase specific activities on the jejunal mucosa were unaltered. Under the light microscope jejunal villi from hypertonic mannitol rats were comparable to controls. Some epithelial cells from rats force-fed hypertonic mannitol showed transient ultrastructural damage. Microvilli of some cells were shortened and fused at their bases 20 and 40 min after the force-feeding. By 120 min epithelial cell microvilli were all normal in appearance. In hypertonically fed rats the lateral interdigitating plasma membranes became disorganized. Large fragments budded off into one cell and fused to form larger structures. By 120 min many lysosomal autophagic vacuoles and residual bodies were seen. A single hypertonic force feeding produced jejunal cell loss associated with loss of brush border disaccharidases and focal ultrastructural damage.Speculation The damage induced in the jejunal mucosa of rats by a hypertonic feeding may provide clues concerning the pathophysiology of certain clinical conditions. Damage to the lateral interdigitating plasma membranes of adjacent epithelial cells could reflect alterations in permeability allowing the passage of bacterial toxins or allergens into the circulation, or permitting massive bacterial gas leakage leading to pneumatosis intestinalis. The loss of jejunal cells and parallel loss of disaccharidases into the intestinal lumen could, in part, account for the disaccharidase deficiences seen in diarrheal disease where osmotic pressure can become significant because of unabsorbed carbohydrate. This malabsorption may be further enhanced by microvillar alterations such as shortening and fusion, which significantly decrease the effective absorptive area.

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

The present findings show that while chronic administration of the catecholamine isoproterenol to immature rats causes accelerated structural development, it causes an inhibition of certain aspects of secretory function. The effects on both structure and function are however closely dependent on the stage of development during which the agent is administered. When the isoproterenol is given for 8 days between 12 and 20 days of age, amylase, Na, and K concentrations of pilocarpine-evoked parotid saliva of the treated and control littermates are similar. If, however, the agent is given between 22 and 30 days of age, amylase of the isoproterenol-treated glands is only one-fourth that of controls, and K concentration is higher than that of controls whereas Na is lower. The glands of controls in both pre- and postweanling groups produce greater volumes of water than do isoproterenol-treated glands. Developmentally, these data represent less advanced secretory abilities, and therefore isoproterenol induces inhibition of secretory capacity, rather than enhancement.Speculation Drugs administered during early postnatal growth may possibly irrevocably modify critical components of function.

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID