摘要:

Menkes' kinky hair syndrome is a lethal Xlinked disorder marked by tissue-specific increases in copper content. An animal model of kinky hair syndrome is provided by mice mutant at the X-linked mottled locus. The basic defect is unknown. In order to discriminate among potential etiologies, we asked whether the expression of the mottled mutation causes abnormalities in the metabolism of trace metals other than copper in hemizygous mottled (blotchy) cultured skin fibroblasts, and whether we can differentiate mutant and normal cells according to their response to metal inducers of metallothionein. Blotchy fibroblasts accumulated up to 12 times more64Cu than control (littermate) cells, over time and over a range of 64Cu concentrations. A saturable high affinity component to64Cu accumulation over a fixed time interval was revealed in these studies. While64Cu uptake kinetics were indistinguishable in mutant and control cells, the patterns of64Cu exit differed. In both cell types, the rate of release of a rapidly exchangeable fraction of newly acquired64Cu was similar. However, in mutant cells, a larger fraction of recently accumulated64Cu is retained. In contrast to the results for64Cu, accumulation and exit of65Zn and109Cd were not distinguishable in mutants and controls. With exposure to either a strong (cadmium) or weaker (zinc) inducer of metallothionein,64Cu accumulation was increased in normal cells, while there was no change from the already elevated level of64Cu accumulation in blotchy cells. In contrast, the effects of metal inducers of metallothionein on65Zn or109Cd accumulation in mutant cells were indistinguishable from the effects on controls. The present observations reveal that blotchy fibroblasts exhibit normal accumulation and exit of metals other than copper, and evince a differential response to metallothionein inducers, which response is also limited to the accumulation of copper. When considered together with the larger body of data on the kinky hair syndrome and mottled mutation, we infer that the defect in both species resides in the function of a thionein or other protein specifically binding copper; or in an altered transport system specifically affecting copper.

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

In the Henderson-Hasselbalch equation, the apparent first dissociation constant for carbonic acid in plasma, pK1, is 6.10 ± 0.01 (±SD) in healthy adults. In contrast, values for pK1in sick adults and in sick infants and children have been reported to vary widely. Because of the far reaching implications of these findings, we repeated the measurements in 19 newborns in a neonatal intensive care unit. Two measurements were made in each infant, one while the infant was acutely ill and another after recovery. We found that neither the mean value nor the range of pK3values was affected by the infants' clinical status. The values during the acute phase of the hospitalization (range, 6.01-6.12; mean ± SD, 6.08 ± 0.03) did not differ from those after recovery (6.02-6.17; 6.08 ± 0.04). A second study was performed in order to see if the wide range of pK1values seen in other studies might be the result of an unstable state accompanying acute changes in acid-base status similar to those that might be encountered in clinical situations. However, data in seven lambs showed no significant difference when pK1before an acute alteration in acid-base status (6.10 ± 0.04) was compared with that 10 min after (6.09 ± 0.03). In newborn intensive care units, nomograms are used to calculate total CO2from pH and Pco2assuming a pK1=6.10. Our data support this practice.

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

A sensitive, simple, and rapid semiautomated sandwich enzyme immunoassay (EIA) was developed for measuring thyrotropin in dried blood samples on filter paper for use in screening for neonatal hypothyroidism. Good correlation was found between values for thyrotropin determined by this method and those determined by radioimmunoassay (RIA) (r=0.94). In pilot tests on 17,160 newborn infants in the general population, five cases of primary hypothyroidism were detected by both EIA and RIA. The recall rate was slightly higher in EIA than in RIA.

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Several previous studies have reported that a substance in exocrine products from cystic fibrosis (CF) patients is inhibitory to the transport of NaCl in several biological preparations. We have recently developed techniques for studying a target CF tissue, the eccrine sweat duct, and determined that salt absorption in the CF sweat duct appears to be decreased due to an impermeability to CI. To determine whether this property might be induced, we have examined the sweat from patients with CF for potential influences on the ion-reabsorptive and ion-selective properties of sweat ducts from normal subjects. Isolated segments of sweat ducts from healthy volunteers were microperfusedin vitrowith concentration-adjusted sweat collected after thermal stimulation from CF patients and from normal subjects. The eccrine sweat duct may be best considered as a tight epithelium through which the mucosal uptake of NaCl proceeds via separate Na+and Cl-pathways. As such, inhibitory actions of CF fluids should be exerted via an inhibition on one, or both, pathways, and should be expected to 1) inhibit the electrolyte transport activity and 2) alter the ion-selective properties of normal ductal tissue. We were unable to detect any effect of CF sweat on either property of the normal duct.

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

The potential role for retinol (vitamin A alcohol) in the differentiation of the developing lung prompted this study in the perinatal rat. High performance liquid chromatography was used to separate, detect, and quantitate retinol and retinyl palmitate in lipid extracts of tissue and serum. Fetal and maternal blood showed the presence of retinol, whereas no retinyl palmitate was detected. On the other hand, fetal and postnatal lungs contained retinyl palmitate as well as retinol. Considerable changes in the content of lung retinyl palmitate were found during lung development. Fetal lungs (17-21 days of gestation) contained 2.3 ± 0.36 µg/g wet weight (mean ± SD) of retinyl palmitate and 0.14 ± 0.05 µg/g of retinol. Lungs of pups (1-10 days old) contained much less retinyl palmitate, 0.63 ± 0.20 µg/g, whereas the amount of retinol was the same as in fetal lungs. The surprisingly high content of retinyl palmitate in fetal lung and its depletion after birth may be functionally related to retinol action in the developing lung.

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Chronic reserpine treatment of adult rats results in the accumulation of pancreatic enzymes and reduction of their discharge. These changes are reminiscent of those in cystic fibrosis. Since the majority of cystic fibrosis patients have their pancreatic dysfunction manifested in childhood, we studied chronic reserpine treatment in rat pups. Four-day-old rat pups were given reserpine (50 µg/kg intraperitoneally) or vehicle daily until sacrifice. The reserpine group showed significant decreases in body weights at 14 and 21 days of age. Pancreatic weights were also decreased but were of normal weight or increased when normalized against body weights. At 14 and 21 days of age, pancreatic concentrations of amylase, lipase, and trypsinogen showed no difference between reserpine and control pups. At both ages, pancreatic contents of all three enzymes were generally less in the treated pups, but were found to be similar when corrected for body weights. Hydrocortisone treatment of 14-day-old pups caused precocious accumulation of pancreatic enzymes in both reserpine and control groups.Intestinal contents of lipase, trypsin, and amylase were decreased in the reserpine pups at 14 days of age and reached a more significant level at 21 days of age; these data suggest a decrease in the secretion of pancreatic enzymes. Dispersed acini from 14-day-old pups showed a reduced capacity to release amylase as stimulated by carbachol or the octapeptide of cholecystokinin. The results suggested that chronic reserpine treatment of pups in the suckling period did not cause significant disturbance of the developmental accumulation of pancreatic enzymes. A definite inhibition of exocrine secretion was found with reserpine treatment. In terms of suppression of enzyme secretion, the results with reserpinized pups resemble the conditions found in cystic fibrosis.

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

The purpose of this study was to evaluate cerebral blood flow and metabolism following pancuronium bromide paralysis in healthy newborn lambs. Cerebral blood flow and cerebral metabolic rate for O2and glucose were measured along with blood pressure and blood gases before and again at 15 and 60 min following pancuronium paralysis in seven newborn lambs. Pancuronium bromide paralysis had no effect on any of these parameters either at 15 or 60 min of paralysis. Total cerebral blood flow, cerebral metabolic rate for O2, and cerebral metabolic rate for glucose were 87 + 6 ml/min/100 g, 258 ± 10 µmol O2/ min/100 g, and 53 ± 10 mmol glucose/min/100 g, respectively. Neither was any change in regional cerebral blood flow noted. In spite of being connected immediately to the ventilator, however, some animals experienced a transient increase (average=32%) in blood pressure, that was not associated with an increase in end tidal CO2. The data suggest that pancuronium paralysis in healthy awake newborn lambs does not lead to any alteration in cerebral blood flow or metabolism.

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

In order to determine the relative roles of O2tension and content, CO2tension, hydrogen ion concentration, arterial blood pressure, and cardiac output in the regulation of fetal cerebral blood flow (CBF), we used radioactively labeled microspheres to measure flow to 20 major brain regions in 24 chronically catheterized fetal lambs. We continually monitored fetal heart rate and blood pressure, and periodically measured arterial Po2, Pco2, pH, and hematocrit. In addition to CBF measurements during control periods, we measured CBF during: 1) hypoxia (O2content<6 mI·dl-1; O2tension<15 torr) induced by having the ewe breathe a gas mixture with low O2concentration, 2) hypercapnia (Pco2>50 torr) induced by increasing the maternal inspired CO2, 3) acidosis and alkalosis (7.60>pH>6.60) induced by infusing lactic acid or bicarbonate into the fetus, and 4) hypotension (blood pressure<35 mm Hg) and hypertension (blood pressure>55 mm Hg) induced by rapidly phlebotomizing or transfusing the fetus. We used multiple regression analysis and analysis of covariance to examine the dependence of total cerebral blood flow on arterial O2tension and content, CO2tension, pH, blood pressure, and cardiac output. The results demonstrated that 1) fetal CBF increased linearly as oxygen tension or content decreased and a hierarchy of responsivity occurred (brainstem>subcortex and cortex), 2) fetal CBF increased as carbon dioxide tension increased with a different hierarchy of responsivity (brainstem>subcortex>cortex), and 3) autoregulation of fetal CBF over a wide range of blood pressure or cardiac output was maintained for both total CBF and the various brain regions examined.

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Estimates of splanchnic energy substrate exchange in the primate infant have been obtained using a baboon model. The splanchnic bed of the fasting baboon newborn released glucose at an estimated rate of 14.5 ± 5.0 µmol/min·kg body weight. Splanchnic glucose release in the fasting 5-7-wk old baboon infant proceeded similarly at an estimated rate of 15.5 ± 4.5 µmol/min·kg body weight. The principal precursors taken up by the splanchnic bed were lactate, glycerol, and alanine. Uptake of alanine correlated in a linear fashion with glucose release. Lactate was the most important precursor in both age groups. Glucose recycling through lactate is an active mechanism in the primate fetus as well as in the young of other species.

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

The frequent inclusion of heparin in fluids used for total parenteral nutrition in infants, prompted an investigation of the ability of heparin to release lipoprotein lipase (LPL) and hepatic lipase (HL) from the endothelial surface into the circulation, and of the effect of heparin on tissue stores of lipase in the postnatal period. In rat pups, plasma postheparin lipolytic activity (PHLA) released by IP administration of heparin (0.5 unit/g body wt) was 15% of adult values at birth and increased rapidly to reach 60% on day 10. Repeated doses of heparin (in adult rats, given 0.1 unit/g IV) at 1 and 4 h after the initial dose did not affect the maximal response to heparin. In all age groups 80% of PHLA was inhibited by 0.5 M NaCl, suggesting a mostly nonhepatic origin for the released enzyme. Heart, lung, and liver lipase activities of rat pups were not significantly different from controls not given heparin. The pattern of change in tissue enzyme content was similar for heart and lung, but different from hepatic lipase. LPL activity in the former increased from 10 and 30% to 60 and 100% of adult values between birth and 10 days while in the latter enzyme activity exceeded adult levels at birth and decreased to 50% of adult values during the latter half of the suckling period (days 10-21). Our results demonstrate that heparin does not cause depletion of tissue lipases in the postnatal period. The parallel increases in LPL content of peripheral tissues and PHLA suggest that in all age groups heparin-induced release of LPL into the circulation is proportional to tissue lipolytic activity.

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID