摘要:

ExtractUptake of L‐cystine at the plasma membrane of fibroblasts derived from normal and cystinotic subjects was studied. L‐Cystine accumulation after a 20‐min period was increased in cystinotic fibroblasts incubated in 0.08 mM L‐cystine. This effect appeared to be concentration‐dependent since accumulation after 20 min at 0.004 mM concentration was decreased in cystinotic cells. Kinetic data suggested that at least two nondiffusional saturable processes with widely different substrate affinities mediate initial L‐cystine uptake in skin fibroblasts. In addition, the transport process with high affinity for L‐cystine may itself be a two‐component system, as suggested by (1) additive inhibtory effect of other neutral amino acids, and (2) preincubation studies in which preincubation with cystathionine enhanced subsequent L‐cystine uptake, whereas preincubation with other neutral amino acids depressed subsequent uptake. Affinity constants and maximal velocities of initial uptake did not appear to be altered in cells derived from patients with cystinosis. After 60‐sec incubation with L‐[35S]cystine, cystinotic cells retained more label as cystine than did normal cells at each concentration studied.These data indicate that initial L‐cystine uptake in fibroblasts of patients with cystinosis proceeds at a normal rate by means of all transport systems currently shown to be present in normal cells.SpeculationL‐Cystine may accumulate in cells of patients with cystinosis because of an alteration in a transport system for L‐cystine which is, as yet, undescribed. Alternatively, L‐cystine accumulation may occur because of a transport defect at the lysosomal membrane which is not expressed at the plasma membrane.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractConversion of adenosine to inosine is decreased in adenosine deaminase (ADA)‐deficient fibroblasts at all concentrations of adenosine tested. Adenosine is not differentially toxic to ADA‐deficient fibroblasts except at very high (5 × 10−4−1 × 10−3M) adenosine levels. Conversion of [14C]adenosine to GTP is not decreased in ADA‐deficient cells compared with control cell strains. Adenosine conversion to ATP is the same as that in mutant cells except at high nonphysiologic concentrations, at which it is slightly decreased in ADA‐deficient fibroblasts. This effect is probably not related to the biochemical pathology of ADA‐deficient lymphocytesin vivo.Uridine, a pyrimidine compound, “rescues” control cells from the effects of adenosine toxicity, as previously reported, but it has no protective effect on ADA‐deficient fibroblasts. This suggests that uridine will have no therapeutic role in the treatment of the ADA‐deficient form of severe combined immunodeficiency (SCID) disease.SpeculationThe purine base, hypoxanthine, may be necessary for normal immunologic responses.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractBeginning at age 10 years, height, weight, body density, and bone age of 40 normal boys were measured yearly over a period of 8 years. From body density, lean body mass and body content of fat were calculated. Values for all measurements are included in the Appendix and mean values, including those for lean body mass and percentage of body fat, are presented for each year in Table 1. Coefficients of correlation between measurements made during the first and eighth years of study were high for height (0.68), weight (0.50), and lean body mass (0.60), but relatively low for body fat (0.25). Correlation coefficients between the various parameters in a given year are presented in Table 2.The maximum yearly increment in height, weight, and lean body mass of individual subjects coincided in time. The respective mean values for the year of maximum growth were 9.4 cm, 8.1 kg, and 7.5 kg. Throughout the growth spurt, the contribution of fat to increase in body weight was small. It may be concluded that, next to height, the absolute amount of lean body mass demonstrates the most constant trend of development during adolescence.SpeculationLean body mass, like weight and height, follows individual patterns that are consistent throughout adolescence. The trends in height and lean body mass are more constant than trends in body weight.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractThis report deals with quantitative and qualitative investigations of alkaline phosphatase in two unrelated infants with the severe infantile form of hypophosphatasia. Both affected infants had no detectable leukocyte alkaline phosphatase activities and both sets of parents and one sibling tended to have low but variable leukocyte enzyme activities. Normal duodenal juice alkaline phosphatase activity was present in the one patient in whom it was measured and a wide range of variation in enzymic activity was observed in the stools. There was no significant difference in the stool enzyme activity between both patients with hypophosphatasia (42.01 ± 9.77 U) and control infants (40.55 ± 6.29 U). However, the heterozygous parents had values significantly lower than the control adults (2.10 ± 0.47 as compared with 19.10 ± 4.44 U). Intestinal bacteria did not contribute significantly to the stool alkaline phosphatase activity. Enzyme activity was present in the bile of one of the patients and nearly absent in that of the other.Three “inducers” of alkaline phosphatase were given to both patients (phenobarbital, vitamin A, and corticosteroid). No clinical improvement or rise in serum alkaline phosphatase activity was observed during the trial of therapy with these agents. However, a significant increase in the activity of serum acid phosphatase was demonstrated during the course of vitamin A administration, suggesting anin vivoaction of vitamin A on the lysosomes through decreasing the stability of the membrane and releasing acid phosphatase to the serum.Quantitative determination of tissue alkaline phosphatases from autopsy tissues was highly variable: no activity was found in bone, lungs, or spleen of either infant; there was a discrepancy in liver and kidney alkaline phosphatase values (zero in one patient and present in the other) and activity was present in the intestinal mucosa of both.Qualitative analysis of kidney, liver, and intestinal alkaline phosphatase revealed some differences between the patients and control subjects in heat inactivation and phenylalanine inhibition (Table 3). Starch gel electrophoresis of the liver preparation of one patient disclosed a single band which had greater mobility than that of six control subjects matched for age. Liver extracts from a premature and from full term newborns showed two bands. The single band of the patient's liver enzyme corresponded to the newborn's fast moving component. In addition, the intestinal enzyme prepared from the same patient had an extra band when compared with age‐matched control subjects.SpeculationAmong the many quantitative and qualitative alterations in alkaline phosphatases found in these two infants with the severe form of hypophosphatasia, the most striking finding was the presence in the liver of one of the cases of what appeared to be a form of the enzyme normally present only during very early postnatal life. The defective regulation of the various alkaline phosphatase isozymic forms during development may thus represent the basic defect in this disease.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractThe effect of catheter placement in the abdominal aorta on the blood flow and oxygenation of lower extremities was evaluated in 30 New Zealand rabbits, weighing 0.55‐3.5 kg, by inserting 3.5 and 5.0 French polyvinyl chloride catheters, of the type commonly used for umbilical artery catheterization, through the femoral artery, advancing 15‐20 cm, and leaving in place for 10‐30 min. Arterial blood pressure (BP), common iliac artery blood flow (BF), gracilis muscle tissue oxygen availability (O2a), and subcutaneous temperature (T) in the foot were continuously monitored before and during catheter placement and after withdrawal. There were no changes in the physiologic variables measured in the contralateral leg when the catheter remained below the aortic bifurcation; however, when the catheter was advanced 15‐20 cm into the abdominal aorta, a decrease in lower extremity BF, O2a, and T occurred. Because the length of catheter insertion was maintained constant in each animal, the decreases in BF, O2a, and T are related to the relative dimensions of the vessel and the catheter. The ratio of catheter to vessel diameter, in addition to the site of catheter placement, should be considered during the clinical application of arterial catheters. Reduction in blood flow could be detected by continuous differential monitoring of core and extremity temperature or extremity muscle oxygen availability.SpeculationPlacement of catheters in the aortas of animals of physical sizes comparable to those of newborn infants may produce an appreciable obstruction to aortic flow. Until a suitable noninvasive method of assessing oxygenation in newborns is available, umbilical artery catheters should be of the smallest possible outside diameter and placed below the bifurcation of the abdominal aorta.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractThis report describes thein vitroanalysis of the series elasticity of ventricular myocardium isolated from five fetal lambs and six adult sheep. Active compliance measurements were obtained by quick releases utilizing a closed loop servosystem and electromagnetic positioning device to control cardiac muscle length or tension. Right ventricular moderator bands were obtained from five fetuses (average 139 days of gestation, term = 147 days), and compared with two adult moderator bands and four adult right ventricular trabeculae carneae. After correction for equipment coupling, the experimental load extension data were fit to an exponential expression by a least squares technique: strain = l/b ln (l + stress/a).When fetal and adult data were compared, no age‐related differences in the constants were observed (a = 0.185 ± 0.062 SE (fetal) and 0.159 ± 0.03g/mm2(adult); b = 40.4 ± 5.2 (fetal) and 43.1 ± 5.2 (adult); and ab = 7.39 ± 2.34 (fetal) and 5.27 ± .99 (adult). However, significant variation existed in the histologically determined amount of contractile tissue present in muscle samples from both fetus (57‐85%, average = 74.0 ± 4.9) and adult (64‐94%, average = 82.3 ± 5.3). Without regard to age, a significant correlation was found between the b stiffness constant and the amount of contractile mass present in cardiac muscle. Thus, it is concluded that there is no age‐related difference in the stiffness of fetal and adult ventricular muscle. However, there is a significant relationship between active compliance and true muscle mass.SpeculationThere is now substantial evidence that isometric force generation in fetal ventricular myocardium is significantly depressed when compared with the adult (3). Moreover, this reduction in the strength of cardiac contraction is not accompanied by a comparable depression in the extrapolated or unloaded velocity of shortening when fetal and adult hearts are compared (3). Several hypotheses have been advanced to explain the depression of force generation in fetal tissue. First, it is clear that there is less contractile tissue per unit volume in fetal myocardium (3, 13); second, a depression of contractile state may exist in fetal cardiac muscle (3). Although the additional contractile tissue present in the adult heart could explain the lesser force generation of fetal myocardium, it is also possible that a more compliant “series elasticity” in fetal muscle could be responsible for an attenuation of force generation, particularly since the unloaded velocities are similar in the two groups of muscle. Indeed, the resting length‐tension relationship of fetal muscle (3) and the non‐normalized pressure‐volume relationship of the whole heart (7, 13) have been shown to be significantly “stiffer” than in adult preparations, although the resting stiffness per unit mass of tissue may not be altered (7). Accordingly, the present study was designed to examine the active compliance of fetal and adult sheep myocardium in order to determine whether age‐related differences exist in “series elasticity” or active stiffness.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractMeconium of human infants and rhesus monkey infants(Macaca mulatta)contained only about 0.10 of the amount of bilirubin in gallbladder bile of the same individuals.Ninety‐nine percent of the bilirubin in adult bile was conjugated. The proportion of conjugated bilirubin in infant bile and meconium was only slightly lower. Adult bile contained more bilirubin diconjugates than monoconjugates, whereas only 20% of the bilirubin in infant bile and meconium was in the form of diconjugates.The predominant azopigment in adult bile was azopigment &dgr; (a glucuronide). Infant bile contained less azopigment &dgr;, more azopigment &agr; (azodipyrrole), and a so far unidentified conjugated azopigment (azopigment &bgr;). Azopigment &bgr; was also found in meconium but adult gallbladder bile contained only trace amounts of this pigment.SpeculationThe metabolism of pigments in human meconium and bile is not yet well understood. To learn more about this area an animal model is required. In this investigation the pigments in adult human bile, infant bile, and meconium were compared with corresponding specimens from nonhuman primates. Our aim was to study the suitability of such an animal model for an investigation of this aspect of neonatal bilirubin metabolism.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractThe skin, brain, lung, liver, and kidney from a 20‐week‐old fetus who was diagnosed as having fetal I‐cell disease by amniocentesis at 14 weeks of gestation were examined by light and electron microscopy. In addition, cultured fibroblasts from the skin were also observed microscopically. Cytoplasmic inclusions with dense polymorphic contents appeared commonly in the capillary endothelial cells in the skin, lung, glomerulus of the kidney, and the epithelial cells of the proximal tubules of the kidney, and sometimes in the hepatocytes of the liver and the nerve and glial cells of the brain. Erythropoietic cells in the liver and circulating erythrocytes contained dense inclusions varying in developmental stages. Fibroblasts of the skin had several clear vacuoles, and cultured fibroblasts were filled with dense inclusions. The dense cytoplasmic inclusions in fetal I‐cell disease were light and electron microscopically similar to the residual bodies which are commonly observed in the phagocytic cells.SpeculationIn fetal I‐cell disease, the cytoplasmic inclusions may first appear as dense bodies in the capillary endothelial cells of fetus as early as 4 weeks of gestation. Material stored in the inclusions may reflect deranged metabolism of the cells. Thus, the morphologic changes of I‐cell disease may be due to the deficiencies of intralysosomal enzymes.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractPseudohypoaldosteronism is an uncommon disorder characterized by urinary sodium wasting and is attributed to a defect in distal renal tubular sodium handling with failure to respond to endogenous aldosterone. Sweat electrolyte values in other reported patients, when measured, have been normal. A 3.5‐year‐old girl developed repeated episodes of dehydration, hyponatremia, and hyperkalemia during the first 19 months of life. Serum sodium was as low as 113 mEq/liter and potassium as high as 11.1 mEq/liter. Her plasma and urinary aldosterone levels were persistently elevated (Figs. 1‐4). Unlike patients with classic pseudohypoaldosteronism she demonstrated no urinary sodium wasting (Figs. 2 and 3). During episodes of hyponatremia and reduced sodium intake her urinary sodium was less than 5 mEq/liter. In addition, her sweat sodium concentration was consistently above 125 mEq/liter and salivary sodium concentration above 58 mEq/liter. Her chest x‐ray, 72‐hr fecal fat excretion, serum and urinary pancreatic amylase (amy‐2) were normal, providing no evidence for cystic fibrosis. It is proposed that this patient represents a new variant of pseudohypoaldosteronism with excessive loss of sodium from the sweat and salivary glands instead of the kidneys.SpectulationAldosterone is known to control sodium and potassium excretion by kidneys, sweat glands, and salivary glands. In patients with classic pseudohypoaldosteronism there is a defect in renal tubular response to aldosterone action. Studies in the present patient suggest that there may be variants of this syndrome in which the end organ defect is in the sweat and salivary glands instead of the renal tubule. In addition, it is possible that new variants will be found in which end organ defect is in still other organs concerned with electrolyte transport.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractPropionic acid significantly inhibited14CO2production from [1‐14C]palmitate at a concentration of 10 &mgr;M in control fibroblasts and 100 &mgr;M in methylmalonic fibroblasts. This inhibition was similar to that produced by 4‐pentenoic acid. Methylmalonic acid also inhibited14CO2production from [1‐14C]palmitate, but only at a concentration of 1 mM in control cells and 5 mM in methylmalonic cells.Propionic acid (5 mM) also inhibited ureagenesis in rat liver slices when ammonia was the substrate but not with aspartate and citrulline as substrates. Propionic acid had no direct effect on either carbamyl phosphate synthetase or ornithine transcarbamylase.These findings may explain the fatty degeneration of the liver and the hyperammonemia in propionic and methylmalonic acidemia.SpeculationIt has been shown that 4‐pentenoic acid will produce may of the features of Reye's syndrome in rats. The fact that propionic acid inhibits some of the same reactions as 4‐pentenoic acid raises the possibility that other short chain fatty acids less unusual than 4‐pentenoic acid could produce the features of Reye's syndrome.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID