摘要:

Concentrations of l-carnitine and acylcarnitines have been determined in urine from patients with disorders of organic acid metabolism associated with an intramitochondrial accumulation of acyl-CoA intermediates. These included propionic acidemia, methylmalonic aciduria, isovaleric acidemia, multicarboxylase deficiency, 3-hydroxy-3-methylglutaric aciduria, methylacetoacetyl- CoA thiolase deficiency, and various dicarboxylic acidurias including glutaric aciduria, medium-chain acyl-CoA dehydrogenase deficiency, and multiple acyl-CoA dehydrogenase deficiency. In all cases, concentrations of acylcarnitines were greatly increased above normal with free carnitine concentrations ranging from undetectable to supranormal values. The ratios of acylcarnitine/carnitine were elevated above the normal value of 2.0 ± 1. 1. l-Carnitine was given to three of these patients; in each case, concentrations of plasma and urine carnitines increased accompanied by a marked increase in concentrations of short-chain acylcarnitines. These acylcarnitines have been examined using fast atom bombardment mass spectrometry in some of these diseases and have been shown to be propionylcarnitine in methylmalonic aciduria and propionic acidemia, isovalerylcarnitine in isovaleric acidemia, and hexanoylcarnitine and octanoylcarnitine in medium-chain acyl-CoA dehydrogenase deficiency. The excretion of these acylcarnitines is compatible with the known accumulation of the corresponding acyl-CoA esters in these diseases.In this group of disorders, the increased acylcarnitine/ carnitine ratio in urine and plasma indicates an imbalance of mitochondrial mass action homeostasis and, hence, of acyl-CoA/CoA ratios. Despite naturally occurring attempts to increase endogeneous l-carnitine biosynthesis, there is insufficient carnitine available to restore the mass action ratio as demonstrated by the further increase in acylcarnitine excretion when patients were given oral l-carnitine. Thus, l-carnitine insufficiency is a general phenomenon in these diseases.

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

We established an experimental animal model of the gastrointestinal colonization and systemic disease following oral challenge of type III group B streptococcal strain in 3-day-old newborn rats. Two type III group B streptococcal strains isolated from the cerebrospinal fluid of septic newborn infants produced colonization in 57-87% of the challenged animals and 13-31% of these colonized animals developed systemic disease. Using this new animal model, we evaluated the effect of orally administered human immune serum globulin on the colonization and systemic disease. This antiserum contained 21 µg/ml of type III group B streptococcal antibody of human IgG class. Animals fed with immune serum globulin developed significantly lower rates of colonization and systemic disease than those of control (albumin or saline) (23 versus l\%,p<0.001 for colonization; 7 versus 31%, p<0.05 for systemic disease). However, rates of the development of systemic disease among the colonized animals were not significantly different between the two groups (33versus43%, p>0.1). These findings suggest that orally administered immune serum globulin is beneficial in the prevention of colonization and systemic disease in this rat model and that this protective effect of oral immune serum globulin occurs primarily at the mucosal level

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Metabolic and enzymatic studies in a patient with hereditary tyrosinemia demonstrated for the first time a deficiency of erythrocyte and hepatic glutathione. Markedly decreased hepatic fumarylacetoacetate hydrolase activity was demonstrated in this patient. The activities of hepatic enzymes not involved in tyrosine metabolism were also determined. Assay of mixed function oxidase activity demonstrated low levels of aryl hydrocarbon hydroxylase and 7-ethoxycoumarin deethylase, suggesting decreased hepatic detoxification capacity. 5-Aminolevulinic acid dehydratase activity was undetectable. Succinylacetone (4,6- dioxoheptanoic acid), an abnormal metabolic product secondary to fumarylacetoacetate hydrolase deficiency was found in serum and urine. Succinylacetone was demonstrated to inhibit 5-aminolevulinic acid dehydratase in vitro, as did the urine, plasma, and red cell Iysates of the patient.

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Recent studies have identified abnormalities in Cl-permeation across two target cystic fibrosis (CF) epithelia (sweat duct and respiratory epithelium). In the present study, anion conductances of red blood cells (RBCs) and peripheral blood lymphocytes (PBLs) from CF and normal subjects were estimated and compared. For RBCs, the valinpmycin-induced rate constant for K+loss (PK+) was taken as an index of Pcl-For PBLs, the secondary volume increase after gramicidin pretreatment and hypotonic (0.67X isotonic) stress was used to estimate Pcl-The CI-permeabilities of RBCsand PBLsfrom CF and control subjects were comparable. These findings suggest that the abnormality in Pcl-reported for CF sweat ductal and respiratory epithelia is not expressed in circulating blood elements.

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

The deficiency of γ-glutamyl transpeptidase activity, which was evident in some but not all cystic fibrosis amniotic fluids, could be corrected by mixing with either normal fluids or nondeficient cystic fibrosis fluids. Incubation of any amniotic fluid for 20 min at 62° C resulted in total loss of γ-glutamyl transpeptidase activity, but the activity could be restored by mixing with untreated nondeficient fluids. In contrast, no restoration could be obtained by mixing with untreated deficient cystic fibrosis fluids. Dialysis of amniotic fluids did not diminish their corrective capacity. Only the transpeptidation reaction was corrected and no correction was observed for the hydrolysis or autotranspeptidation of γ-glutamyl p-nitroanilide in the absence of the glycylglycine or methionine acceptor. Plasma specimens did not have any corrective activity, although their γ-glutamyl transpeptidase activity could be restored after heat inactivation by mixing with untreated nondeficient amniotic fluids. No correction was found for aminopeptidase or disaccharidase activities. These findings suggest that the deficient cystic fibrosis amniotic fluids probably contain normal quantities of the γ-glutamyl transpeptidase enzyme but lack a heat-labile nondialyzable activator that is necessary for its transpeptidation catalytic performance. An assay for this transpeptidase activator may provide a valuable approach to identify at least a subgroup of cystic fibrosis patients.

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

This study was conducted to investigate myocardial excitation-contraction coupling in the fetus of the diabetic rabbit (FDM). On day 14 of gestation, diabetes was induced in pregnant rabbits by alloxan injection. On day 28 of gestation, mechanical function of the fetal myocardium was determined in the isolated arterially perfused heart preparation. At 1.5 mM [Ca2+]o(control), the force of myocardial contraction in FDM was not significantly dfferent from that in the control fetus. At higher [Ca2+]o, developed tension and maximal rate of tension development [+dT/dt (max)] in FDM were significantly greater than in the control fetus. High [Ca2+]ocaused significant increases in resting tension and half-relaxation time (toxic effects) in the control fetus, but not in FDM. Perfusion with lanthanum (known to displace sarcolemma-bound Ca2+and block sarcolemmal Na-Ca exchange) decreased developed tension and +dT/dt (max) and increased resting tension and these effects in FDM were significantly less than in the control fetus. Perfusion with manganese (known to displace Ca2+from intracellular sites) also decreased developed tension and +dT/dt (max) and increased resting tension, and these effects were similar in the two groups. The myofibrillar ATPase activities at various calcium concentrations were not different between the two groups. The rates of Ca2+uptake by mitochondria and sarcoplasmic reticulum were similar in the two groups. These data suggest that in FDM the inotropic effect of Ca2+is greater and the toxic effect of Ca2+is less than in the control fetus. This difference may be due, at least in part, to a sarcolemmal alteration induced by the maternal diabetes.

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Essential fatty acid deficiency (EFAD) occurs in infants fed fat-free mixtures of glucose and amino acids. Although infusion of lipid emulsion rapidly reverses clinical symptoms, little is known about effects on tissue fatty acids. To study this question, five groups (n=4/ group) of neonatal pigs were studied. Three groups (I, II, and V) were made EFAD by feeding diets without essential fatty acids (EFA) for days 5 to 33 of life. Groups III and IV were fed a control diet. By 33 days, animals fed the deficient diet showed clinical symptoms and biochemical signs of EFAD. On days 33 to 54 of life, group I animals were fed the EFA-deficient diet and infused with lipid emulsion, providing 3.6% of energy as linoleic acid; group II animals were fed the deficient diet and infused with linoleic acid at 7.2% of energy; group V animals were fed the deficient diet with no lipid emulsion; group III and IV animals were fed the EFA-deficient diet and provided EFA intravenously. Infusion of lipid emulsion rapidly reversed clinical symptoms of EFAD and returned plasma phospholipidω6 fatty acids levels to normal. However, erythrocyte and liver phospholipidω6 fatty acid content and adipose tissue reserves ofω6 fatty acids normalized more slowly. Three weeks of infusion of linoleic acid at 3.6% of energy and 2 weeks of infusion at 7.2% of energy were required to return erythrocyte phospholipid fatty acids to normal. Liver phospholipid fatty acid composition still showed biochemical evidence of EFAD in animals treated with linoleic acid at 3.6% of energy for 3 wk. Adipose tissue reserves ofω6 fatty acids did not return to normal in animals treated for 3 wk with linoleic acid at 3.6% of energy. Two to 3 wk of treatment with linoleic acid at 7.2% of energy was required to return adipose tissue 6ωfatty acids reserves to normal.

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Aggregation of red blood cells (RBC) is a major determinant of blood viscosity and of blood circulation through vessels with slow flow (i.e. veins). RBC aggregation and plasma fibrinogen were studied in placental blood samples from 25 neonates with 24 to 41 wk of gestation and in blood from 13 normal adults. The rate and final extent of RBC aggregation were measured by means of a rheoscope (increase in light transmission during blood stasis). Both the rate and extent of RBC aggregation were low in the premature infants, increased with gestational age, and reached the highest values in the adults. Blood from seven infants with 24 to 28 wk of gestation did not show any significant RBC aggregation during the first minute of stasis. RBC aggregation was closely related to the fibrinogen level. Cross-suspension studies (neonatal RBC in adult plasma and adult RBC in neonatal plasma) showed that neonatal and adult RBC had the same aggregation pattern when they were suspended in the same plasma. Moreover, neonatal and adult RBC demonstrated the same strong aggregation when they were resuspended in 1% dextran. These results indicate that specific plasma properties are responsible for the decreased RBC aggregation observed in the neonates while their specific RBC properties do not affect RBC aggregation.

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

The adherence of bacteria to pediatric IV catheters and needles was studied. Scanning electron micrographs showed that bacteria adhered well to the catheters and needles, mainly to non-smooth surface areas.In vitroquantitative determination, with the use of radiolabeled bacteria, revealed differences in the affinity of bacteria for the various IV cannula materials. The adherence per square area was greatest for plastic catheters, less for steel needles, and least for siliconized needles. Mean values for the adherence of Staphylococcus aureus to these cannulae were 37.9-40.3 x 105bacteria/cm2for the plastic catheters; 10.2 x 105bacteria/cm2for the steel needles, and 7.2-7.6 x 105/cm2for the siliconized needles. Removal of the glutaraldehyde-fixed bacteria adhered to the cannulae, after their placement in veins of rabbits, was lower for the plastic catheters than the IV needles. The appearance and severity of venous phlebitis produced by the various cannulae was determined in an animal model. The degree of the inflammatory response elicited correlated with thein vitrobacterial adherence, indicating that bacterial adherence plays a role in the appearance of cannulaassociated phlebitis.In view of our results and other previous observations of lower rate of infections with the use of IV needles, it is suggested that needles should be preferred to plastic catheters whenever possible. The describedin vitroassay for bacterial adherence can be used to determine the adherent properties of IV cannulae, which should be considered in any future cannula design.

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Since postnatal development of the gastrointestinal tract has an important effect on its microbial flora and may influence the types of intestinal infections, we examined the effect of age on bacterial adherence to intestinal epithelial cells. Radiolabeled bacteria were incubated with guinea pig enterocytes released by treating loops of the intestine with solutions containing EDTA, dithiothreitol, and citrate. Nonbound bacteria were separated from intestinal cells by sedimentation on a Percoll gradient. The colonic cells avidly boundShigella flexneri(64 bacteria per cell),Escherichia coli0124 (59), andE. coli0128 (53). The adherence process was Ca2+and temperature dependent, was inhibited by fucose, glucose, and mannose, and was shown to be mediated by a carbohydrate-binding protein (lectin) on the colonic cells. Adherence of these bacteria to intestinal cells of newborn animals was only 15- 25% of the adherence to adult animal cells and increased gradually, reaching adult values at about 2 weeks of age. The lectin activity, which was determined by agglutination of bacteria, was secreted with the colonic mucus. It was undetectable in the newborn animal, appeared gradually with age, and its titer correlated with the adherent capability of the colonic cells.E. coli0128 was the only one of the bacteria tested which significantly adhered to the ileum (19 bacteria per cell) in a process inhibited by mannose. This adherence was mediated by a mannose-sensitive lectin in the bacterial pili, and not on the intestinal cells. The postnatal age had no effect on the adherence to the ileum; the newborn animal had the same adherence capability as the adult one. Good correlation was found between the adherence to the suspended intestinal cells and the adherence to intact intestinal surfaces or thein vivoadherence to intestinal loops.These patterns of bacterial adherence can be important in the neonatal microbial colonization of the intestinal tract, and can play a role in the types of intestinal infections during the neonatal period and infancy.

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID