摘要:

Intrauterine and early postnatal malnutrition caused a marked and protracted weight reduction of the body, spleen, and thymus. The mean body weight of the offspring of the malnourished mothers at weaning was 25 ± 10 g whereas that of the controls was 75 ± 20 g. At weaning the mean spleen weight of the malnourished offspring was 0.19 ± 0.05 g and that of their controls was 0.4 ± 0.13 g. During refeeding the spleen weight but not the thymus weight of the malnourished offspring caught up with that of the controls after about 70 days. After refeeding for as long as 4 months the thymus weight of the malnourished was still significantly (P< 0.01) less than that of the corresponding weight‐matched controls. Primary and secondary plaque‐forming cells (PFC) in both the spleen and thymus of the weanling malnourished offspring were barely detectable whereas spleen of their controls had mean approximate values of 50 × 103primary PFC and 70 × 103secondary PFC. The corre‐sponding values in the control thymus were 20 × 102primary PFC and 8 × 102secondary PFC.After refeeding for 4 months of the weanling malnourished offspring their primary and secondary PFC in the spleen increased to about one‐half the level of that in their controls whereas the PFC in the thymus were still barely detectable. On the other hand, mean primary and secondary rosette‐forming cells (RFC) in the spleen of the weanling malnourished offspring were less than 1 × 103in comparison to the 80‐90 × 103in the controls (P< 0.001). In the thymus too, mean primary and secondary RFC were also less than 1 × 103, whereas the corresponding figure in the controls was 30‐50 × 103RFC. After refeeding for 4 months the mean values of both the primary and secondary RFC in the spleen and thymus continued to remain less than 1 × 103.Although cell morphology in the spleen of the malnourished offspring had returned to normal appearance after 4 months of refeeding, that of the corresponding thymus had not done so completely. For instance, thymic corticomedullary function had reappeared by this time but thymocytes were still less in number than in the controls. By the 8th postnatal day serum IgG2b allotype became detectable in the control offspring, but it was not untilday 20that this IgG allotype could be detected in the malnourished offspring. IgG2a allotype could be detected in the sera of both the malnourished and control offspring.SpeculationImpairment of cell‐mediated immune response caused by intrauterine and neonatal protein‐calorie malnutrition is probably responsible for the skin, oral, and respiratory tract infections seen in children with early protein‐calorie malnutrition. Thymic reconstitution might play a significant role in the treatment of these children. This speculation is now being investigated.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractA 9‐year‐old boy with severe mental and growth retardation and diffuse neurologic damage had minimal elevation of blood pyruvate (0.21 mM) and lactate (2.1 mM) on a normal diet but developed life‐threatening lactic acidosis (pH 7.14; lactate 21.0 mM) on a diet containing 65% carbohydrates and 15% fat. Subsequently, blood pyruvate levels rose significantly higher than in 16 control subjects during a glucose tolerance test whereas the glucose levels were normal.Two sisters died with spontaneous lactic acidosis and an otherwise similar clinical course. Their brains at autopsy were severely deficient in myelin but showed no evidence for active demyelination.Cultured skin fibroblasts from the patient oxidized [1‐14C]pyruvate (0.16 ± 0.07 cpm/mg protein/min) and [2‐14C]pyruvate (0.10 ± 0.03) to14CO2at a significantly slower rate than control cells (0.93 ± 0.03 and 0.30 ± 0.02;P< 0.001), but oxidized [1‐14C] palmitate, [1,5‐14C]citrate, [U‐14C]glutamate, and [1‐14C]valine normally. The activity of the pyruvate dehydrogenase complex in cell‐free extracts (59 ± 16 pmol/min/mg protein) was significantly less than that for control subjects (389 ± 35;P< 0.001), but the activities of pyruvate decarboxylase and of the 2‐oxoglutarate dehydrogenase complex were within the normal range. Pyruvate dehydrogenase levels in extracts of the parents' cells were midway between those of the patients and the control subjects. Mixing experiments, addition of excess cofactor, and studies of activation failed to implicate a soluble inhibitor, abnormal binding of cofactors, or defective activation as causes of the reduced enzyme activity.The data are consistent with an inherited defect in the seconed enzyme of the pyruvate dehydrogenase complex, lipoate acetyl‐transferase (EC. 2.3.1.12). The defect appears to be inherited in an autosomal recessive manner.SpeculationDiets low in carbohydrate and enriched in fats may benefit patients with pyruvate dehydrogenase deficiency.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractData are presented for erythrocyte protoporphyrin (EP) concentrations determined by the direct reading technique of Lamolaet al.(1). Mean concentration of EP in children whose blood lead concentration was less than 30 &mgr;g/dl was 34.7 &mgr;g/dl whole blood ± 13.4 (SD). Mean EP concentration in children with blood lead concentrations of 40‐59 &mgr;g/dl was 80.8 &mgr;g/dl. It was 158 &mgr;g/dl for children with blood lead concentrations greater than 59 &mgr;g/dl. All children in this last group had concordant values for Pb and EP on the first or second test.SpeculationScreening for lead poisoning using capillary blood determination of erythrocyte protoporphyrin as determined by the direct reading dedicated fluorometer is adequate for ascertaining all children in possible need of immediate treatment. The authors believe, however, that screening should be done using both EP and blood lead determinations. The goal of lead poisoning control programs is to eliminate childhood lead poisoning by preventing exposure to lead hazards. Even after elimination of values from children with transient elevation of blood lead concentrations and those with falsely elevated concentrations because of contamination or laboratory error there is a significant number of children with blood lead concentrations of 40‐59 &mgr;g/dl who do not have elevated EP concentrations. Opportunities for protecting these children from further lead paint hazards will be lost.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractTo test the hypothesis that fetal lung maturation can be accelerated by one of the xanthine derivatives, aminophyllin was given to 40 pregnant rabbits beginning on the 20th gestational day for a period of 7‐10 days. The fetuses were delivered by cesarean section and fetal lung maturity was assessed by determining the biochemical, functional, and ultrastructural characteristics of aminophyllin‐treatedvs.control animals. The phospholipid content of the lung tissue homogenate from the aminophyllin‐treated group was significantly higher than in the control subjects (saline injected) at 28 days of gestation (421 ± 9vs.368 ± 12 &mgr;g/mg wet wt, mean ± SEM) and at 29 days of gestation (531 ± 10vs.475 ± 20). The alveolar wash phospholipid content of the aminophyllin‐treated group was higher at 30 days (167 ± 9 &mgr;g/mg dry wt, mean ± SEMvs.117 ± 17). The lung compliance derived from pressure volume curves was also significantly higher in the aminophyllin‐treated group when compared with controls at 27 days of gestation (0.023 ± 0.0005 ml/cm H2O, mean ± SEMvs0.010 ± 0.0002) and at 28 days of gestation (0.048 ± 0.0003vs0.035 ± 0.0006). There was no significant difference in the number of lamellar bodies in the type II cells between the aminophyllin‐treated and the control groups. The data show that aminophyllin has accelerating effects on fetal lung maturation in rabbits when the drug is given to pregnant rabbits during the last 7‐10 days of gestation.SpeculationOur data do not permit extrapolation into the clinical application of utilizing xanthine derivatives for the enhancement of fetal lung maturation. However, they provide evidence that there may be several pharmacologic agents that might enhance fetal lung maturation by various mechanisms. These data may also provide impetus for some centers to review the statistical correlation of respiratory distress syndrome in infants born to mothers who have received xanthine derivatives during the latter part of pregnancy for the treatment of such conditions as bronchial asthma. If the latter clinical evidence is a positive one, it may be justified to initiate a clinical trial to evaluate the effect of xanthine derivative treatment of the mother for the purpose of preventing respiratory distress syndrome in the newborn infant.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractOral tryptophan loading tests were performed in a patient with photosensitive pellagra‐like skin rash and cerebellar ataxia but without hyperaminoaciduria. Plasma tryptophan concentrations after loading were similar in the patient and control subjects. Average urinary excretion of tryptophan in the patient from 0 to 6 and 6 to 12 hr was 2.69 and 2.58 &mgr;mol/kg, respectively; that in the control subjects was 0.82 and 0.34 &mgr;mol/kg, respectively. However, the average renal clearance of tryptophan during the first 6 hr of the loading tests in the patient was 0.757 ml plasma/1.73 m2and that in the control subjects was 0.706 ml plasma/1.73 m2.Renal excretion of kynurenine in the patient was markedly decreased. The average from 0 to 6 and 6 to 12 hr in the patient was 1.90 and 1.13 &mgr;mol/kg, respectively; that in the control subjects was 12.90 and 18.15 &mgr;mol/kg, respectively. Under ultraviolet light, paper chromatograms of urine from the patient showed a deficiency of xanthurenic acid, kynurenic acid, kynurenine, and formylkynurenine. The deficiency of formylkynurenine in the patient's urine was confirmed by staining the paper chromatograms with Ehrlich's reagent.The patient was “sensitive” to oral nicotinic acid treatment; however, oral nicotinamide was well tolerated with improvement in the photosensitive skin rash.SpeculationThe normal absorption of tryptophan and the marked decrease of formylkynurenine and kynurenine in the urine after tryptophan loading in this patient suggest a metabolic block in tryptophan oxidation. The lack of formylkynurenine excretion suggests a deficiency of tryptophan pyrrolase (L‐tryptophan 2,3‐dioxygenase).

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractDietary pyridoxine deficiency induced in postweanling rats led to severe growth retardation and growth failure, with a sharp increase in the mortality rate after about 8 weeks on the diet. The absolute weights of heart, lungs, kidneys, and adrenals were all lower in the deficient animals than those of the controls. However, when the weights were expressed in terms of percentage of body weight, a 2‐fold increase was observed indicative of marked hypertrophy. The depletion of the coenzyme pyridoxal‐5′‐phosphate from these tissues was extensive (heart 48%, lungs 85%, and kidneys and adrenals 88%). The extent of loss of the coenzyme from the tissues suggests possible functional changes.SpeculationFunctional disturbances may be expected as a consequence of the marked hypertrophy and the extensive depletion of the coenzyme pyridoxal‐5′‐phosphate from the heart, lungs, kidneys, and adrenals in postweanling pyridoxine‐deficient rats.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractA previously described assay for iduronate sulfatase has been adapted for use with serum, lymphocytes, and fibroblasts. The assay also gives a rough measure of iduronidase activity. We have evaluated the procedure for the diagnosis of the Hunter syndrome, for the detection of Hunter heterozygotes, and for the diagnosis of certain other disorders (mucolipidoses II and III and mucopolysac‐charidosis I).Hunter patients had 1‐2% normal iduronate sulfatase activity in the three sources tested. The serum assay is undoubtedly the method of choice to establish the diagnosis of the Hunter syndrome. Less than 1 ml serum and 3‐4 days are required to complete the procedure.Serum could not be used for the detection of iduronidase deficiency diseases, but these could easily be recognized in lymphocyte and fibroblast preparations.The iduronate sulfatase activity of sera from patients with mucolipidoses II and III was elevated 20‐fold, but their parents had a normal level of this enzyme. In fibroblasts of patients with mucolipidoses II and III, both iduronate sulfatase and iduronidase activities were markedly decreased.Serum assays were not informative about the Hunter heterozygote status. However, the mean activity in lymphocytes from mothers of Hunter patients was about half of the mean normal activity. A number of obligate heterozygotes had iduronate sulfatase activity so low that they were identifiable as carriers; others, unfortunately, had a clearly normal level. The possibility of carrier detection by the lymphocyte assay needs further development.SpeculationThe procedure described shows markedly reduced iduronate sulfatase activity in lymphocytes of half the obligate heterozygotes tested; with further refinements, it may form the basis of a carrier detection test.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractFetal intrauterine growth retardation was induced in nine rats at 17 days' gestation by ligating the blood supply to one of the uterine horns. The 27 fetuses from the uterine vessel ligated side were the intrauterine growth retarded fetuses (IUGR) and the 37 fetuses from the nonligated side were controls. The mean weight of the IUGR fetuses was 3.4 ± 0.3 g which was significantly smaller (P< 0.005) than the mean weight of the control fetuses, 4.0 ± 0.3 g.Whole body histidine decarboxylase (HDC) activity was assayed by a radioisotope method. The HDC activity per g tissue was not correlated to body weight in the control fetuses. This is in contrast to the IUGR fetuses in which the HDC per g tissue was significantly and inversely related to body weight (r− 0.48,P< 0.001).SpeculationIncreased histidine decarboxylase activity and histamine formation are generally associated with increased growth. Fetal rat intrauterine growth retardation was correlated with increased HDC activity. This suggests that the growth‐retarded fetuses were attempting to maintain growth by increasing HDC activity and histamine formation.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractNine Sicilian children known to be deficient in glucose‐6‐phosphate dehydrogenase (G6PD) were studied to see if there were anomalies of bactericidal activity in peripheral blood phagocytes. The type of deficiency was established. The G6PD levels in the leukocyte were found to be 26% of the controls (0.094 ± 0.03, normal controls 0.360 ± 0.12). The Michaelis constant for NADP and glucose‐6‐phosphate (G6P) was lower than the control. Conversely, the utilization of the analogous 2‐deoxyglucose‐6‐phosphate (2dG6P) and galactose‐6‐phosphate (Ga16P) was higher. The thermostability of the enzyme in the deficient subjects was lower and the pH optima (8 and 9.5) were different from the controls. An identical electrophoretic pattern was found in both normal and deficient subjects. The bactericidal activity in the deficient subjects was normal. There was no difference in the results of nitroblue tetrazolium (NBT) tests in either group.SpeculationAlthough leukocyte G6PD was only one‐quarter of the normal level, the phagocytic activity and the NBT test were normal in all subjects studied. It is not clear how such low levels of enzyme allow normal function. Perhaps further investigation under simulated intracellular conditions could give more reliable information about the enzyme activity.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractSections of pancreas from 16 individuals who died with cystic fibrosis (CF) were classified by morphometric criteria into four categories in increasing order of pancreatic involvement. The concentration of acini, islets, main ducts, lobular ducts, connective tissue, and fat was compared with control levels. The results show that in the least involved pancreases, from neonates who died under 5 months of age, acini were reduced to 33% of control levels and the following were increased: islets, to 410%; lobular ducts, to 250%; and main ducts, to 1700% of controls.With increasing severity of the pancreatic disease the acini were further reduced to 5% and lobular ducts to 37% of control levels, respectively. Main ducts increased by 19‐fold, and fatty infiltration accounted for more than 25% of the fresh weight of the pancreas in 9 of the 16 specimens.Comparative biochemical studies of 35 fibrocystic pancreases were quantitatively related to the severity of the pancreatic involvement as follows. Water and volatile matter, normally accounting for 80±% of the weight of the fresh pancreas, was reduced to less than 30% in the most affected organs. The concentration of zinc diminished from near normal mean levels of 193 &mgr;g Zn/g dry pancreas to 10% of this amount in the severely involved pancreas.Elevated concentrations of calcium, amounting to over 10 times control level, were found in obstructed ductal structures. Calcium was depleted from pancreatic sections adjacent to the obstructions. The following biochemical indicators were significantly different in their mean levels in the 35 fibrocystic pancreases when compared with the 17 controls: (P≤ 0.001) fat, water, zinc, calcium, copper, magnesiu, potassium, and sodium (P≤ 0.01).SpeculationMorphometric and biochemical studies of the pancreas in cystic fibrosis are interpreted to favor an early and perhaps primary role of ductal and ductular abnormality in the pathogenesis of the pancreatic lesion. The principal basis for this suggestion lies in the demonstration of early massive enlargement of the ductular system and the consequent accumulation of viscous calcium‐rich inspissated material responsible for the formation of functional ductal obstructions. Alterations in calcium concentration and binding in the pancreas and in pancreatic juice are believed to be responsible for changes in membrane permeability and the transport of water and electrolytes. The pancreatic disease process beginsin uteroand the degeneration of the pancreas progresses through life in nearly all patients with cystic fibrosis.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID