摘要:

SummaryA 7-week-old infant with methylmalonic acidemia had pancytopenia and hypoplastic bone marrow. The patient responded to large doses of vitamin B12 treatment, and within 3 wk, the blood counts and bone marrow cellularity returned to normal. To understand the mechanism of marrow depression in this infant, we examined the effect of the patient's plasma and methylmalonic acid itself on thein vitrogrowth of bone marrow-committed stem cells. The patient's plasma obtained before B12 treatment completely inhibited the marrow cell growth, whereas the posttreatment plasma showed no inhibition. Methylmalonic acid when added to the culture dishes in concentrations comparable to those reported in plasma of methylmalonic acidemia patients, inhibited growth of marrow stem cells in a concentration-dependent fashion. On the other hand, 16 to 18 hr incubation of cells in the same concentration of methylmalonic acid did not affect the recovery or viability of the cells. The observations suggest that methylmalonic acid is inhibitory to the proliferation of marrow stem cells. The mechanism of inhibition is yet to be elucidated.SpeculationMMA at a concentration comparable to that reported in patients with methylmalonic acidemia inhibitedin vitrogrowth of marrow hemopoietic cells, but overnight incubation of the cells in MMA at the same concentration did not reduce the number of viable cells determined by the trypan blue dye exclusion test. It appears, therefore, that MMA within the range of concentration tested is not immediately cytotoxic. Its inhibitory action thus seems to require longer cell contact hours than the 16 to 18 hr we used, and it may be directed against rapidly proliferating cell population. The potential mechanisms of inhibition are unknown and more work is needed to understand the interaction of MMA with hemopoietic cells.

ISSN:0031-3998    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SummaryTwenty-five cases of acute ketoacidosis, occurring in insulin-treated diabetic children in previous good health, were studied close to the onset of illness and throughout the first 24 hr of therapy. In most patients, symptoms of illness and ketonuria had been present for less than 12 hr; in 9 subjects, they had been present for less than 4 hr. Initial plasma glucose concentrations ranged from 252 to 849 mg/dl. The first pH values in 21 cases were less than 7.27, and in the remaining 4 studies, the CO2was less than 14 mEq/liter. Identifiable sources of stress, such as infections or emotional arousal, preceded the development of ketoacidosis in 20 cases.Serial measurements were made of plasma glucocorticoid, growth hormone, and glucagon concentrations as well as urinary excretion of epinephrine and norepinephrine to assess the role of these hormones in acute ketoacidosis and to evaluate their relationship to the abnormalities in glucose and electrolyte homeostasis. Excessive urinary excretion of epinephrine was a frequent and striking phenomenon. Output was greater than 4 S.D. above the mean in 20 of 23 cases in the first 2 hr of the study. In 15 cases, the values fell into the normal range by approximately 14.5 hr, but in seven patients, epinephrine overproduction persisted for the entire study. Cortisol hypersecretion was present in 24 of 25 patients and persisted for 6 to 8 hr or longer before gradually subsiding. Initial growth hormone concentrations were elevated in seven patients (20 ng/ml or above), but the highest values (20 to 160 ng/ml) were observed after insulin administration. At the outset, plasma glucagon concentrations were less than 200 pg/ml in 11 patients; in 11 others, it ranged between 250 and 1250 pg/ml. The elevated values usually were transient. Of 22 cases in whom all five hormones were measured at the start of the study, 21 exhibited increased production of at least three of the stress hormones.We conclude that some diabetic children who have received their usual dose of insulin develop hyperglycemia, dehydration, and acidosis within a few hr of experiencing stress because large amounts of counterregulatory hormones, especially catecholamines and cortisol, are released.SpeculationAcute onset of ketoacidosis in previously healthy insulin-treated diabetic children occurs because their daily dose of insulin is insufficient to offset the effects of the counterregulatory hormones produced in response to stress (catecholamines, cortisol, glucagon, and growth hormone). Hyperglycemia, dehydration, and acidosis result from the glycogenolytic, lipolytic, and ketogenic action of the stress hormones.

ISSN:0031-3998    

出版商:OVID    

年代:1981

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1981

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SummaryThe effect of undernutrition during suckling has been investigated on the brush border enzymes and the intestinal uptake of D-glucose and glycine in rats at weaning. The brush border sucrase and alkaline phosphatase activities were drastically reduced, but lactase and leucine aminopeptidase levels were significantly elevated in the intestine of nutritionally deprived pups compared to controls. The uptake of D-glucose and glycine in undernourished rats was also augmented. The chemical composition of the brush border membrane analyzed in nutritionally deficient animals revealed an enhancement of the membrane protein, sialic acid, cholesterol, and phospholipids compared to the control group. [U-14C]D-Glucose incorporation into lipid constituents of the membrane suggested that the observed enhancement of the membrane lipids is the result of an increased synthesis in response to undernutrition.SpeculationIt may be surmised that undernutrition induced postnatally influences the structural and functional organization of the brush border membrane because of delayed maturation of the epithelial tissue. Endocrine disturbances in undernutrition may be implicated to the observed phenomenon.

ISSN:0031-3998    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SummaryUrinary excretion of orotic acid was measured in controls and in subjects homozygous and heterozygous for lysinuric protein intolerance under various conditions of amino nitrogen intake. In all situations, the controls excreted less than 28 μg/kg/hr. Only one of the two heterozygotes studied differed from the controls. The orotic aciduria of homozygotes was normal in fasting but increased on a self-chosen low-protein diet (log mean, 80; range, 8 to 588 μg/kg/hr in 24-hr urine), after cow's milk protein, 0.5 g/kg (769; 251 to 1747 μg/kg/hr in 4 to 6-hr urine), oral ammonium lactate, 2.5 mmoles/kg (95; 15 to 1127 μg/kg/hr in 1.5-hr urine), and IV alanine, 6.6 mmoles/kg (519; 47 to 1831 μg/kg/hr in 6-hr urine).Giving ornithine or citrulline IV with the infusion of alanine prevented the increase in orotic acid excretion. Given orally, citrulline was more efficient than ornithine or arginine. To prevent the hyperammonemic and orotic aciduric responses with ornithine, its plasma concentrations needed to be higher than normal.Orotic aciduria is a reliable indicator of the function of the urea cycle in lysinuric protein intolerance and facilitates monitoring of the treatment of this disease.SpeculationThe parallel changes in urinary orotic acid and blood ammonia concentrations in lysinuric protein intolerance suggest a close link between the urea cycle and the pyrimidine pathway, probably via carbamyl phosphate and asparate. Follow-up of orotic aciduria is a simple and presumably accurate method for monitoring the home treatment of disorders of the urea cycle.

ISSN:0031-3998    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SummaryIt has been known for some time that the viscosity of sputum from cystic fibrosis (CF) patients differs from that in other disease types characterized by pulmonary hypersecretion. However, it has never been established that there is in fact any abnormality in the rheologic properties of CF sputum. We have recently developed techniques to examine the rheology and mucociliary transportability of tracheal secretions from dogs utilizing the small quantities of mucus available from a healthy animal. In the present study, thesein vitrotechniques were applied to sputum samples obtained from 15 adult CF patients. For mucoid and mucopurulent CF sputum samples, the viscoelastic properties were remarkably similar to those observed for control canine tracheal mucus samples. For purulent CF sputum, elasticity and viscosity tended to be higher and the viscosity/elasticity ratio lower than for either the nonpurulent sputum or the canine tracheal mucus. The logarithm of elasticity at 1 rad/sec was 2.55 ± 0.35 (S.D.) for purulent sputum, 2.05 ± 0.49 for mucoid and mucopurulent sputum, and 2.17 ± 0.36 for canine tracheal mucus.From the viscoelastic properties of CF sputum, one would have predicted thein vitromucociliary transportability, at least for the nonpurulent samples, to be the same as that of canine tracheal mucus. However, the frog palate assay indicated a consistently lower rate of transport (mean difference, 13%) than that predicted from previous studies. This result would, therefore, suggest that if the prediction from canine tracheal mucus is applicable there is a factor in the CF sputum that results in a temporary inhibition of frog palate ciliary beating. This apparent inhibition of mucociliary transport is, however, relatively minor, and it is perhaps more remarkable that for none of the sputum samples collected was thein vitrociliary transport rate particularly low;i.e., observed values ranged from 65 to 100% of frog palate control.SpeculationThere is probably no rheologic abnormality in the tracheal mucus of patients with cystic fibrosis other than that associated with purulence. Cystic fibrosis sputum can be moved reasonably well by ciliary action, but there is, nevertheless, some suggestion of the presence of a ciliary inhibitory factor in it.

ISSN:0031-3998    

出版商:OVID    

年代:1981

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SummaryYoung rats, rabbits, guinea pigs, and hamsters were decreased in body weight by 39, 45, 34, and 35%, respectively, by a total deprivation of food for 3, 15, 4, and 4.5 days, respectively. The weight of the heart, liver, and kidneys from each of the four species (with the exception of the kidneys from the guinea pig) decreased significantly in the starved animals. After starvation in all four species, 0 to 15% of the original weight of the epididymal and perirenal fat pads remained. The effect of total starvation on the weight of skeletal muscles differed for the same muscle in different species and among the three muscles studied within a species. Starvation caused weight losses in the following muscles from the rat, rabbit, guinea pig, and hamster, respectively: soleus, 15, 8, 14, and 30% plantaris, 23, 54, 41, and 24%; biceps brachii, 27, 52, 42, and 29%. The significant loss of weight in the plantaris and biceps brachii muscles from rabbits and guinea pigs were caused by large decreases in the diameter of the fibers, with no change in the number of fibers. Soleus and plantaris muscles from hamsters decreased in weight by a reduction in fiber diameters but no change in the number of fibers; the weight of the biceps brachii decreased by a reduction in fiber number only. A reduction in the number of fibers occurred in all muscles from starved rats; the diameter of the fibers was reduced in the plantaris and biceps brachii muscles. No structural damage to the fibers due to starvation was observed under the light microscope in any muscle from the four species.SpeculationThe effect of starvation on the weight of several tissues and the cellularity of skeletal muscles varied considerably among the young of four species. Some frequently studied animal models may not replicate accurately the changes observed in tissue weight and in muscle cellularity observed in severely undernourished children.

ISSN:0031-3998    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SummaryRed cell glycolytic intermediates and enzymes in term infants in the first year of life were correlated with the fetal hemoglobin concentration (%F), intra- and extracellular venous pH, plasma inorganic phosphorus (Pi) and pyruvate kinase (PK) activity. Changes in the non-age-dependent enzymes phosphoglycerate kinase, enolase, and phosphofructokinase correlated most significantly with the postnatal decline in %F (P< 0.001), not the age of the red cell population, as reflected in PK activity. The age-dependent enzymes, hexokinase and glucose-6-phosphate dehydrogenase, however, correlated well with PK activity (P< 0.001). The concentration of glucose-6-phosphate did not correlate significantly with the postnatal decline in %F (P> 0.05) or PK (P> 0.10), but correlated significantly with the plasma Piconcentration (P< 0.001). “Total triose phosphate” and 2,3-diphosphoglycerate did not correlate with Pi.It appears from these studies that an extracellular factor, Pi, alters the pattern of glycolytic intermediates in term infants and that the postnatal changes in phosphoglycerate kinase, enolase, and phosphofructokinase are unique to the “fetal” red cell and reflect passage from fetal to “adult” erythropoiesis.SpeculationIt is proposed that the rise in the glucose-6-phosphate concentration in red cells from term infants previously reported is secondary to a combination of stimulation of hexokinase activity by plasma inorganic phosphorus and a relative block in glycolysis at the phosphofructokinase (PFK) step secondary to both decreased enzyme activity and decreased activation of PFK by plasma inorganic phosphorus. It is speculated from these studies that the relative block in glycolysis at the PFK step previously described in term infants is probably greater at thein vivolevel than that predicted from enzyme activity under optimalin vitroconditions.

ISSN:0031-3998    

出版商:OVID    

年代:1981

数据来源: OVID