Why should infants with sleep apneas and apparent life-threatening events be recorded polygraphically?
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Humans↗
Biomedical subjects
P Franco
Publications and source records attributed to P Franco.
Anterior fontanelle pressure variations during sleep in healthy infants.
Our aim was to study the intracranial pressure (ICP) variations during sleep normal infants. Using a noninvasive method, ICP was measured continuously during polysomnography in 12 healthy infants aged from 1 to 11 months (median 3.5 months). We analyzed the variations of mean basal ICP, mean basal pulse pressure amplitude and maximal amplitude of both plateau and B-like waves between transient sleep, quiet sleep and rapid eye movement (REM) sleep. Mean ICP, mean pulse pressure amplitude and B-like wave amplitude increased significantly during transient sleep and REM sleep. Plateau waves occurred during transient sleep and especially REM sleep. By contrast, noninvasive ICP recordings were relatively flat during quiet sleep stages 2 and 3. ICP variations and pressure waves seem to be related to cerebrovascular changes associated with sleep. The physiological ICP variations during sleep must be known in order to allow correct interpretation of continuous ICP measurements in infants.
Humans↗
Tissue distribution of soluble and receptor-bound urokinase in human breast cancer using a panel of monoclonal antibodies.
Current evidence regarding the regulation of urokinase-dependent extracellular proteolysis indicates that plasminogen activation is a surface-associated process. We have compared the histological localization of urokinase plasminogen activator (uPA) and urokinase plasminogen activator receptor (uPAR) in breast cancer sections using a panel of monoclonal antibodies. First, the ability of six different anti-uPA monoclonal antibodies to recognize pro-uPA, uPA, and in vitro-formed complexes of uPA with either soluble uPAR or with plasminogen activator inhibitor type 1 was compared. Then the reactivity of the anti-uPAR antibodies was tested, and the occurrence of an uPA receptor of about M(r) 55,000 in samples from breast carcinoma was assessed by immunoprecipitating the uPA receptor from an in vitro 125I-labeled tumor extract. Immunocytochemical data from adjacent sections of 10 tumor specimens showed that antibodies recognizing free and bound uPA mostly stain the cytoplasm and the membrane of epithelial tumor cells in confined areas of the tumor and some fibroblast-like stromal cells. Acid pretreatment of tumor sections, which removes receptor-bound uPA, causes a strong reduction of the immunocytochemical reactivity of epithelial tumor cells, whereas staining of fibroblast-like cells is not considerably affected. Consistent with these results, epithelial tumor cells were mostly unreactive to anti-uPAR antibodies unless pretreated with acidic buffer, whereas fibroblast-like stromal cells showed a faint but acid-resistant staining with all anti-uPARs. In conclusion, these results show that occupied uPA receptors are definitely present on the membrane of epithelial tumor cells and suggest the occurrence of uPA-uPAR-dependent proteolytic activity on the surface of breast cancer cells.
Adult↗
Mechanisms of obstructive sleep apneas in infants.
During sleep, infants with obstructive sleep apneas are characterised by snoring, laborious breathing, and profuse sweating. During wakefulness, they may have breath-holding spells, and during feeding, difficult breathing and swallowing coordination. Abnormal weight, difficult growth, and recurring ear infections may also develop. During sleep apneas, cinefluoroscopy shows approximation of tongue and hypopharyngeal tissues, with an obliteration of the air space. The obstructed breaths occur mainly in REM, and light NREM sleep, associated with total short sleep time, and frequent arousals. Preterm infants, and term neonates are more prone to obstructive apneas than older healthy infants. Apneas are more frequently seen in boys and in case of excess in body weight. Obstructive apneas are frequently associated with upper airway anatomic abnormalities: malformations, soft tissue infiltration, and neurologic lesions impairing muscle contractions. Alterations of the autonomic nervous control may induce airways obstructions. Contributing factors include mucopolysaccharide storage disease, hypothyroidism, or Down's syndrome. Superimposed factors may occur, such as nasal obstruction, secretions in the airways, or tissue edema. Pressure- and chemo-sensitive reflexes may also favor obstruction. Environmental factors also contribute to the development of sleep apneas: body position, neck flexion, sleep deprivation, or the effects of sedative drugs.
Airway Resistance↗
Immunologic study of orthotopic liver-small bowel transplantation in the pig.
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Animals↗
Prenatal exposure to cigarettes in infants with obstructive sleep apneas.
OBJECTIVE: To investigate the effect of prenatal smoking on infant respiratory behavior during sleep. METHODS: A questionnaire concerning family habits and infants' history was completed for 550 healthy infants before a 9-hour night polysomnographic study. Because the data for 41 infants were not available for analysis, 509 subjects were studied: 115 were newborns evaluated within 1 week after birth, and 394 were healthy infants admitted at 11 weeks of life (range 5 to 29 weeks) after various research protocols. RESULTS: According to the smoking frequency of the mothers during pregnancy, the subjects were defined as "nonsmokers" (no cigarette smoked during pregnancy; n = 400), "light smokers" (1 to 9 cigarettes per day; n = 37), or "smokers" (10 or more cigarettes per day; n = 72). Compared with nonsmokers and light smokers, "smoking" mothers had a significant increase in the number of episodes of uterine bleeding during the pregnancy. Their infants had lower birth weights and more frequent episodes of profuse sweating during sleep. Infants of smokers also had more frequent and longer obstructive sleep apneas than those of the two other groups. For infants of smokers the relative risk for obstructive apneas was 2.76 (95% confidence interval: 1.63 to 4.69; P = .001). The relation between prenatal smoking and postnatal manifestation of obstructive sleep apneas demonstrated a dose-response pattern. Paternal smoking during pregnancy increased the risk of obstructive apneas only in the infants of smoking mothers, but not in those of the two other groups. Maternal smoking after birth did not add significantly to the risk of obstructive apneas. The effect of smoking was seen in older infants, as well as in the newborn not yet exposed to ambient cigarette smoke. A stepwise logistic regression, using obstructive sleep apneas as the dependent variable identified three significant independent variables: smoking during pregnancy (P = .001), profuse sweating during sleep (P = .001), and birth weight (P = .010). No explanation was found for the effect of prenatal smoking on obstructive sleep apneas. CONCLUSION: Prenatal smoking by mothers correlated with an increase in frequency and length of obstructive apneas and a decrease in birth weight of their infants. The infants were under greater risk for obstructive apnea if both parents smoked. Explanations for our results are unknown to us, but these findings may be of interest in the study of infant breathing behavior and epidemiological characteristics of sudden infant death syndrome.
Adolescent↗
Down regulation of Qa gene expression on drug-modified tumor cells.
BACKGROUND: Mouse leukemia, L1210, strongly enhances its immunogenicity following in vivo treatment with 5-(3-3'-dimethyl-1-triazeno) imidazole-4-carboxamide (DTIC). Previous experiments have shown that transformed cells elicit a cell-mediated response accountable for rejection and resistance to a subsequent injection of parental tumor into a syngeneic host. L1210 expresses classical H-2 class I molecules, and since it has been shown that DTIC treatment does not modify the expression of these molecules, this is a suitable model to study nonclassical class I antigens, such as Qa2 glycoproteins, and their potential role in tumorigenicity. METHODS: Cloned cells from L1210 were treated with DTIC and then H-2D, and Qa antigen expression was studied on four clones, before and after xenogenization with DTIC. RESULTS AND CONCLUSIONS: a strong decrease of Qa2 molecule expression was demonstrated by radioimmunoassay and immunofluorescent staining and was confirmed by FACS and 2D-gel analysis. The presence or the absence of Qa antigens on tumor cells could thus be involved in tolerance or rejection of tumor cells in syngeneic animals.
Animals↗
Clinical symptoms associated with brief obstructive sleep apnea in normal infants.
Relatively little data exist concerning the manifestations of repeated obstructive sleep apnea in normal infants. A questionnaire concerning daytime and sleep habits was completed by the parents of 4,100 healthy infants before they underwent a 9-hour night monitoring study. One hundred infants with an obstructive apnea index above 1.2 were randomly selected. They formed the "apnea" group. From the initial population, 300 infants with no apnea were also selected to form the "no-apnea" group. Both groups were matched for sex, gestational age, post conceptional age, birth weight, mother's age, parity and a family history of sudden infant death. Five variables from the questionnaires significantly differentiated the two groups of infants. When awake, the infants with apnea were characterized by a greater frequency of breathholding spells (22% of apnea infants) and episodes of fatigue during feeding (28%) than the non-apnea infants. During sleep, they exhibited a greater frequency of profuse sweating (15%), snoring (26%) or noisy breathing (44%). Multiple symptoms were present in some infants. A stepwise logistic regression resulted in two significant independent variables: profuse sweating during sleep (p = 0.008) and noisy breathing (p = 0.002). The predictive value of these two symptoms was tested on a new group of 650 healthy infants. The two independent variables led to the correct classification of 60 of the 67 infants with apnea (89.67%) and 382 of the 583 non-apnea infants (65.5%). A positive history alone had a positive predictive value of 0.21.(ABSTRACT TRUNCATED AT 250 WORDS)
Electrocardiography↗
Oligonucleotide degradation contributes to resistance to antisense compounds.
A subline of the human B cell lymphoma DHL-4, grown in the artificial serum-free medium HB101, displayed a resistant phenotype to the activity of an antisense oligodeoxynucleotide (aODN) effective on the parental DHL-4 line. It was found that the cellular uptake of the 18mer aODN in the two cell lines was almost the same. In contrast, the unresponsive subline DHL-4r degraded the aODN very efficiently, in contrast to the stability of aODN inside cells of the parental DHL-4 line. Activation of the degrading 'machinery' combined with selective properties of the artificial medium may be responsible for the loss of responsiveness to aODN.
Antineoplastic Agents↗
Clinical problems in relation to apparent life-threatening events in infants.
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Autonomic Nervous System Diseases↗
Ca2+ transport pathways in brush-border membrane vesicles of crustacean antennal glands.
Calcium uptake by brush-border membrane vesicles of Atlantic lobster (Homarus americanus) kidneys (antennal glands) in independent experiments was stimulated by outwardly directed Na or H gradients. In the absence of external amiloride, 45Ca uptake was strongly stimulated by an outwardly directed Na gradient, and this stimulation was enhanced by the addition of an inside-negative membrane potential. External amiloride (2 mM) reduced 45Ca uptake sixfold and lowered sensitivity to membrane potential. 45Ca influx kinetics (2.5-s uptake) in the presence of an outwardly directed H gradient and inside-negative membrane potential were composed of three components: 1) an amiloride-sensitive carrier system, 2) an amiloride-insensitive carrier system, and 3) a verapamil- and membrane potential-sensitive process that may represent diffusional transfer through a calcium channel. It was concluded that 45Ca entry by the amiloride-sensitive process occurred by a previously described electrogenic 2 Na-1 H antiport mechanism [Ahearn, G., and L. Clay. Am. J. Physiol. 257 (Regulatory Integrative Comp. Physiol. 26): R484-R493, 1989; Am. J. Physiol. 259 (Renal Fluid Electrolyte Physiol. 28): F758-F767, 1990; Ahearn, G., P. Franco, and L. Clay. J. Membr. Biol. 116: 215-226, 1990]. 45Ca influx by the amiloride-insensitive mechanism occurred by an apparent electroneutral 1 Ca-2 Na exchange. Transport stoichiometry of the latter mechanism was tentatively established by experiments determining intravesicular Na binding properties and by its apparent lack of response to a membrane potential. At physiological Na, Ca, and H concentrations in the antennal gland lumen and epithelial cytosol, these three calcium transport pathways individually may make significant contributions to net calcium reabsorption to the blood.
Amiloride↗
[Type I familial pseudohypoparathyroidism: clinical and hormonal study].
Pseudohypoparathyroidism is a rare disease characterized by a target tissue resistance to the action of the parathyroid hormone (PTH). Frequently, others hormonal disorders can be associated. We report a family with pseudohypoparathyroidism type I, and discuss the clinical-hormonal alterations founded; it is emphasized that while there were no phenotypical differences among the family members; from the hormonal features point of view, some differences do exist, and several degrees of peripheral resistance were noted.
Adult↗
Prone or supine body position and sleep characteristics in infants.
OBJECTIVE: To evaluate the potential relation between body position and sleep characteristics in normal infants. PATIENTS: Two groups of 3-month-old healthy infants were evaluated: 40 infants who usually slept supine, and 40 who usually slept prone. The two groups were matched for gender, gestational age, postnatal age, birth weight, and total recording time. RECORDING TECHNIQUES: The 80 infants were studied polygraphically during one night in the pediatric sleep laboratory. They were allowed to fall asleep in their usual sleep position, and every 3 hours were gently turned from prone to supine, or from supine to prone. RESULTS: In each group, 6 infants were excluded from the analysis, because they woke up after having been turned over. In both groups, no significant difference was seen between the prone and the supine body positions for the following variables: number of sleep state changes; number of gross body movements; percent of rapid eye movement sleep; saturation with oxygen, arterial blood levels; number and duration of acid esophageal reflux; rectal temperature; mean respiratory rates; water evaporation rates from the forehead skin; and number or duration of central or of obstructive apneas. In both groups of infants, prone body position was associated with a significant increase in sleep duration (+16%) and in non-rapid eye movement sleep (+25%) and a significant decrease in number of arousals (-40%) and in their duration (-43%). CONCLUSIONS: No explanation has been found for the sleep-promoting effect of prone body positioning. The finding could be of interest to the study of infants' sleep quality, as well as to the potential relation between body positions and sudden death during sleep.
Female↗
Separation and characterization of nonphosphorylated and serine-phosphorylated urokinase. Catalytic properties and sensitivity to plasminogen activator inhibitor type 1.
Urokinase synthesized by human A431 epidermoid carcinoma cells is phosphorylated on serine (Mastronicola, M. R., Stoppelli, M. P., Migliaccio, A., Auricchio, F., and Blasi, F. (1990) FEBS Lett. 266, 109-114). To test the possibility that phosphorylation may have specific effects on urokinase function, the phosphorylated and nonphosphorylated forms of urokinase were separated by Fe(3+)-Sepharose chromatography. Both forms exhibit indistinguishable Km and kcat for plasminogen activation. On the other hand, their sensitivity toward the specific plasminogen activator inhibitor type 1 is different as assessed by measuring both the stability of the covalent complex and the residual enzymatic activity. Phosphorylated urokinase was 50% inhibited at a concentration of plasminogen activator inhibitor type 1 4-fold higher than nonphosphorylated urokinase (0.7 versus 0.15 nM). Furthermore about 10% of phosphorylated urokinase was resistant to plasminogen activator inhibitor type 1 at a concentration as high as 20 nM. Thus, phosphorylation affects urokinase sensitivity to plasminogen activator inhibitor type 1, therefore resulting in a net, although indirect, increase of urokinase activity. These results suggest the existence of a novel cellular regulatory mechanism of extracellular proteolysis.
Catalysis↗
Sleep and cardiorespiratory characteristics of infant victims of sudden death: a prospective case-control study.
We studied the polygraphic sleep recordings of 30 infants who eventually died of sudden infant death syndrome (SIDS) and those of 60 matched control infants. All records were extracted from 20,750 sleep studies collected prospectively in 10 sleep laboratories. Of the 30 future SIDS victims, 5 were siblings of SIDS victims and 9 were studied after an apparent life-threatening event. For each SIDS victim, two normal control infants were matched for sex, gestational age, postnatal age and weight at birth. The future SIDS infants were reported to have more frequent episodes of regurgitations after feeding (p = 0.01) and profuse sweating during sleep (p = 0.01) than the control subjects. Only two polysomnographic variables characterized the future SIDS infants. Compared to control subjects, the SIDS infants moved less during sleep (p = 0.04) and had significantly more frequent obstructed breathing events. Obstructive and mixed apneas were seen in 23 of 30 future SIDS victims, but in only 9 of 60 control subjects (p = 0.01). The obstructed and mixed apneas lasted longer in the SIDS than in the control infants (p = 0.01) but did not exceed 15 seconds. The obstructed breaths occurred mainly in rapid eye movement sleep (78% of the events) and were accompanied by drops in heart rates to 68 beats per minute and in SaO2 levels to 75%. The present report adds further indirect evidence for a possible sleep-related impairment of respiratory control in some infants who eventually died of SIDS.
Case-Control Studies↗
Electrogenic 2 Na+/1 H+ exchange in crustaceans.
Hepatopancreatic brush border membrane vesicles of the freshwater prawn, Macrobrachium rosenbergii and the marine lobster, Homarus americanus exhibited 22Na uptake which was Cl-independent, amiloride sensitive, and stimulated by a transmembrane H gradient (Hi greater than Ho). Sodium influx by vesicles of both species were sigmoidal functions of [Na]o, yielding Hill coefficients that were not significantly different (P greater than 0.5) than 2.0. Estimations of half-saturation constants (KNa) were 82.2 mM (prawn) and 280.1 mM (lobster), suggesting a possible adaptation of this transporter to environmental salinity. Trans-stimulation and cis-inhibition experiments involving variable [H] suggested that the exchangers in both species possessed single internal cation binding sites (pK 6.5-6.7) and two external cation binding sites (prawn, pK 4.0 and 5.7; lobster pK 3.5 and 6.1). Similar cis inhibition studies using amiloride as a competitive inhibitor of Na uptake supported the occurrence of dual external sites (prawn, Ki50 and 1520 microM; lobster Ki9 and 340 microM). Electrogenic Na/H exchange by vesicles from both crustaceans was demonstrated using equilibrium shift experiments where a transmembrane potential was used as the only driving force for the transport event. Transport stoichiometries of the antiporters were determined using Static Head analysis where driving forces for cation transfer were balanced using a 10:1 Na gradient, a 100:1 H gradient, and a stoichiometry of 2.0. These electrogenic 2 Na/1 H exchangers appear thermodynamically capable of generating sufficient gastric acidification for organismic digestive activities.
Amiloride↗
Comparative study of the therapeutic effect of photoactivated hematoporphyrin derivative and aluminum disulfonated phthalocyanines on tumor bearing mice.
Although the hematoporphyrin derivative (Hpd) is one of the most studied photosensitisers for photodynamic therapy (PDT), it is far from ideal. Therefore, many laboratories have been investigating a new group of sensitisers, the phthalocyanines. Particularly, in our laboratory we decided to study the aluminum disulfonated phthalocyanines (AlS2PC). They are chemically stable, readily soluble in water and have a strong absorption in the red part of the spectrum at 675 nm. Mice bearing the MS-2 fibrosarcoma treated with 5 mg/kg of AlS2PC survived indefinitely also using a low laser power of 100 mW/cm2 X 10' of exposure time, in contrast to experiments carried out with Hpd where the optical therapeutic laser power was 400 mW/cm2 X 10' and the dose of Hpd was 25 mg/kg. Furthermore, treatment of mice bearing the highly metastatic tumor, B16 melanoma, with 5 mg/kg of AlS2PC and laser light (100 mW/cm2 X 10'), significantly prolonged the survival time in respect to mice treated with 25 mg/kg of Hpd and laser light (400 mW/cm2 X 10').
Animals↗
Sodium and calcium share the electrogenic 2 Na(+)-1 H+ antiporter in crustacean antennal glands.
Na uptake by short-circuited epithelial brush-border membrane vesicles of Atlantic lobster (Homarus americanus) antennal gland labyrinth was Cl independent, amiloride sensitive, and stimulated by a transmembrane H+ gradient [( H]i greater than [H]o; i is internal, o is external). Na influx (2.5-s uptake) was a sigmoidal function of [Na]o (25-400 mM) when pHi = 5.0 and pHo = 8.0 and followed the Hill equation for binding cooperatively [apparent maximal influx (Jmax) = 271 nmol.mg protein-1.s-1, apparent affinity constant for Na (KNa) = 310 mM Na, and Hill coefficient (n) = 2.41]. Amiloride acted as a competitive inhibitor of Na binding to two external sites with markedly dissimilar apparent amiloride affinities (Ki1 = 14 microM; Ki2 = 1,340 mM). Electrogenic Na-H antiport by these vesicles was demonstrated by equilibrium-shift experiments in which an imposed transmembrane electrical potential difference was the only driving force for exchange. A transport stoichiometry of 2 Na to 1 H was demonstrated with the static-head technique in which a balance of driving forces was attained with 10:1 Na gradient and 100:1 H gradient. External Ca, like amiloride, was a strong competitive inhibitor of Na-H exchange, acting at two sites on the outer vesicular face with markedly different apparent divalent cation affinities (Ki1 = 20 microM; Ki2 = 500 microM). Ca-H exchange by electrogenic Na-H antiporter was demonstrated in complete absence of Na by use of an outward H gradient in presence and absence of amiloride. Both external amiloride (Ki1 = 70 microM; Ki2 = 500 microM) and Na (Ki1 = 12 mM; Ki2 = 380 mM) were competitive inhibitors of Ca-H exchange. These results suggest that the electrogenic 2 Na-1 H exchanger characterized for this crustacean epithelium may also have a role in organismic Ca balance.
Amiloride↗