摘要:

ExtractTwo milk-specific glycoprotein fractions and serum orosomucoid were isolated from mature human milk. One of the milk-specific glycoproteins was homogeneous and was termed glycoprotein A. Its sedimentation and diffusion constants were 2.6 S and 6.3 F, respectively, giving a molecular weight of 29,500. It contained some 70% carbohydrate consisting of sialic acid, galactose, fucose, glucosamine, and galactosamine. It was not immunologically related to serum orosomucoid. The other glycoprotein, called glycoprotein B, was heterogeneous with an average molecular weight of near 4,000, and carbohydrate comprised some 75% of its weight. Both glycoprotein fractions supported the growth ofLactobacillus bifidusvar.Penn.Removal of sialic acid enhanced the growth-promoting activity of glycoprotein B but not of A.SpeculationMature human milk whey contains a number of glycoproteins that stimulate the growth ofL. bifidusvar.Penn.These glycoproteins may act in concert with the well known oligosaccharides to maintain an acid environment in the infant's gastrointestinal tract.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractThe effect of protein binding on the rate of placental transfer of hexanoic (C 6) and decanoic (C 10) acids was investigated in anin vitroperfusion system of human placenta. As much as 30% of transferred C 6 was converted to more polar compounds; so that the observations related to the combined effects on transfer and metabolism. Less than 10% of C 10 was similarly metabolized. Both fatty acids are soluble in buffered salt solutions at the concentrations used (40 μM) and both are bound to serum albumin, C-10 having higher association constants (K‘ for C 6, 1.48 x 104; for C 10, 1.03 x 105). When the placenta is perfused with buffered salt solution, the transfer of C 6 is 22% more rapid than that of C 10. It is suggested that binding within the placenta retards C 10 more than C 6. The addition of 1 g/100 ml bovine serum albumin to the maternal perfusate reduces the transfer rate of C 10 by 80%, whereas 2 g/100 ml serum albumin has a more moderate effect on C 6 (a reduction of 50%). The addition of 1 g/100 ml serum albumin to the fetal perfusate increases transfer rate of both free fatty acids (FFA), C 6 by about 25% and C 10 by about 250%. With equivalent concentrations of serum albumin in maternal and fetal perfusates, the transfer rate of C 10 was reduced by 65%, whereas there was no detectable effect on transfer of C 6 in two of three experiments.The transfer rates of FFA increase logarithmically with progressive shortening of the carbon chain from C 16 to C 8 when maternal and fetal perfusates contain serum albumin. Protein binding is apparently the determining factor. The rate of transfer falls off at C 6 and C 4, even though protein-binding continues to decrease. The determining factor may be the hydrophilic nature of these molecules.SpeculationIf the observations on FFA have general applicability, the overall effect of protein binding on placental transfer of a particular substance may relate to its water solubility and protein binding. If water solubility is not a limiting factor, protein binding may decrease transfer rate sharply, as occurs with decanoic acid (C 10). With substances that have very limited water solubility, protein binding may increase transfer by increasing the amount presented to the placenta. Palmitic acid (C 16) appears to be such a compound. The fraction bound to proteins in the perfusate, as measured by equilibrium dialysis, may not be the most significant factor determining rates of transfer. More significant may be the competitive aspects of binding in the perfusate and to the placenta in influencing rates of release and uptake.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractThe investigation was designed to explore the use of tests tapping reversible aspects of behavior and performance and to find out whether these data can be correlated with concurrent metabolic changes in different dietary phases. The four subjects had classic phenylketonuria, diagnosed on the basis of a high level of serum phenylalanine on a regular diet, and severe mental retardation. Three types of diet were used: the general institutional diet, a low phenylalanine diet, and a low phenylalanine diet with added L-phenylalanine. A position discrimination and reversal task was used. Blood samples were taken every week on the day before psychological testing, and one 24-hr urine sample was collected during each dietary phase.Insubjects IandIIperformance deteriorated upon elevation of the serum phenylalanine level, but these changes were transient only, thus showing an adaptation to the effects of the high serum phenylalanine level.Subject IIIshowed increased response latencies (slower test responses) during high phenylalanine diet phases and faster responses while on a low phenylalanine diet. The correlation between response time and phenylalanine level is highly significant (r= 0.86,P< 0.001).On the low phenylalanine dietsubject IV'sresponses were fast and her performance was very stable, which contrasted with erratic performance during the high phenylalanine phases. Calculations show a significant association with phenylalanine level, both for response time (r= 0.47,P< 0.05) and for variability in response time within each session (r= 0.46,P< 0.05).Biochemical variability was observed in metabolic responses to phenylalanine loading, especially in the excretion of tryptophan metabolites.SpeculationA simultaneous analysis of biochemical and behavioral parameters in sufficient detail to permit the detection of individual variability is shown to be feasible. Further studies of a similar nature on a larger scale should help to achieve a more precise understanding of the biochemical processes in the nervous system which are responsible for the behavioral changes.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

Extractγ-Glutamyltranspeptidase (GGTP) activity was studied in livers of rats submitted to an end-to-side portacaval shunt (PCS) and in developing animals. To correlate the evolution of the enzymatic activity measuredin vitro, histochemical techniques were used to localize enzyme activity in liver tissue. The GGTP activity in the adult rats was low and amounted to 2.0 ± 0.1 μmol/min/g. During fetal development the enzyme activity rose beginning on the 15th gestational day from 630 ± 97 to 1,058 ± 20 on the first postnatal day. Then the values declined and reached nearly adult values from the 10th postnatal day.After PCS the GGTP activity exhibited a three- to sixfold increase (130 ± 69 to 371 ± 131) as compared with uneperated adult controls (53 ± 13). The highest levels corresponded to those observed between the 3rd and 5th postnatal day in the developing rats.The histochemistry of GGTP in the fetal and newborn liver showed a regular distribution of the enzyme as a fine deposit in the hepatocytes throughout the whole tissue. Ten days after birth the activity was low, at the same level as in the adult rat. In the period after PCS hepatocytes began to show signs of enzymatic activity at the periphery of the hepatic lobules, which subsequently spread through the whole lobules. The increase of GGTP activity after PCS equaled the activity found in fetal animals. That correlated well in both groups with the reappearance of histologically demonstrable enzyme activity in hepatocytes.SpeculationThe consequences of portacaval shunt might be associated with the derepression of an enzyme normally present only in fetal and neonatal rat liver. Since GGTP plays a role in the γ-glutamyl cycle, and is responsible, supposedly, for the transport of amino acids into the cell, it may be that in fetal liver and after PCS augmented cellular amino acid transport is an expression of growth and transformation processes.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractThe effect of glycine administration on acute leucine loading (125 mg/kg) was tested in a patient with isovaleric acidemia. Serum isovaleric acid at 1 3/4 hr after the leucine loading alone was elevated to 5.60 mg/100 ml and urinary isovalerylglycine excretion was 9.90 mg/mg creatinine/24 hr. When the same amount of leucine was given with glycine (250 mg/kg) serum isovaleric acid was only 0.93 mg/100 ml. Unfortunately, urine was collected for only 12 hr after the leucine-glycine loading. However, the amount of urinary isovalerylglycine was 26.2 mg/mg creatinine in this period. In the following experiments in which a meal containing 80 mg leucine/kg was given, serum isovaleric acid was elevated to 1.14 and 1.01 mg/100 ml at 3 hr and 6 hr after the loading, respectively. How-ever, serum isovaleric acid was only 0.53 and 0.79 mg/100 ml at 3 and 6 hr, respectively, when the identical mean was given with 2 g glycine.The effect of long term glycine administration (250 mg/kg/24hr) was also tested. It did not prevent two ketotic episodes which were caused by infections. However, the duration of clinical symptoms such as vomiting and a large anion gap in the acute episodes were much shorter with rectal glycine administration. The patient's linear growth and weight gain during glycine administration was much belter than that in the pretreatment period.SpeculationIn isovaleric acidemia, isovaleryl-CoA is not oxidized because of an inborn deficiency of isovaleryl-CoA dehydrogenase activity. The leucine loading tests and clinical response to oral glycine in this patient suggest that exogenously administered glycine enhanced the conjugation of glycine with isovaleryl-CoA, thus preventing accumulation of free isovaleric acid, a toxic substance. With glycine administration, mitochondrial glycine concentration seems to be elevated to a level at which faster reaction velocity of glycine-N-acylation of isovaleryl-CoA is attained. Thus, glycine administration appears to be an effective therapeutic method in the management of acute ketoacidotic episodes in this disease. However, chronic administration failed to prevent ketoacidotic episodes which were induced by infections.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractThe relationship between glomerular filtration rate and proximal tubular fluid reabsorption was evaluated in control rats and in rats 96 and 144 hr after the injection of an aminonucleoside of puromycin. Urine volume and sodium excretion were decreased in the rats injected with aminonucleoside. Proteinuria increased progressively. Total kidney glomerular filtration rate (GFR) was diminished less than surface nephron GFR at 96 hr and greater than single nephron GFR at 144 hr after injection when a large proportion of nephrons are nonfunctional. Clearance ofp-aminohippurate was unchanged initially and depressed subsequently after aminonucleoside injection. Absolute reabsorption to the end of the proximal convolution was unaltered despite a decrease in total kidney filtration fraction. This decrease in GFR coupled with unchanged absolute reabsorption and hence increased fractional proximal reabsorption leads to decreased delivery of sodium and fluid to the more distal portions of the nephron.SpeculationGlomerular filtration rate is decreased in rats with aminonucleoside nephrosis. Absolute reabsorption along the proximal tubule is not reduced proportionally. The increase in fractional reabsorption which results coupled with a decrease in GFR may be an important source of fluid and sodium retention and thus edema formation in this disease.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractIn an effort to characterize the hepatic abnormality in patients with α1-antitrypsin deficiency, three unrelated children with the disorder (Pi types ZZ and SZ), two heterozygous parents (Pi type MZ), and three normal subjects (Pi type MM) were studied. As expected, the livers of the ZZ- and SZ-deficient subjects showed abnormal accumulation of α1-antitrypsin in the cisternae of the rough endoplasmic reticulum as judged by immunofluorescent and electron microscopic studies. Their parents (MZ phenotype) demonstrated identical although less extensive hepatic abnormalities. Short term cultures of liver tissue in the presence of radiolabeled amino acids showed both synthesis and release of α1-antitrypsin in normal control subjects and in the patients with the Z protein. Radiolabeled intracellular α1-antitrypsin could not be found. These studies demonstrate synthesis of α1-antitrypsin by the livers of normal and genetically deficient subjectsin vitro, and suggest several possible mechanisms for α1-antitrypsin deficiency.SpeculationStudiesin vitroof the synthesis and release of α1-antitrypsin, as shown in the present investigation, may reveal the molecular basis of this genetic disorder.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractModified stereotaxic techniques were applied to fetal lambs during the latter third of gestation. Electrical stimulation in the region of the hypothalamus in 10 acute experiments was associated with three patterns of arterial blood pressure and heart rate changes: a pressor-tachycardia response; a pure tachycardia response (abolished by propranolol); and a pure bradycardia response (abolished by atropine). The pressor-tachycardia response was examined in detail in 13 chronic preparations (115–135 days of gestation at operation). The systolic arterial blood pressure increase was never greater than 35 mm Hg and was probably blunted by the large noninnervated placental circulation. This pressure increase was abolished by phentolamine and was thus mediated by stimulation of α-adrenergic receptors. The initial tachycardia was prevented by propranolol and was due to β-adrenergic stimulation. The tachycardia was followed in a few seconds by a bradycardia, abolished by atropine and possibly a vagal baroreflex. The pressor-tachycardia response was accentuated in two lambs who were delivered spontaneously and were studied after birth. These studies indicate that a suprabulbar neural framework exists in the fetal lamb for influencing the cardiovascular system from as early as 90 days of gestation.SpeculationSince electrical stimulation in the region of the hypothalamus is associated with various changes in blood pressure and heart rate, it is possible that the upper brain stem in the late gestation fetus has a role in the central nervous regulation of the circulation. Complex cardiovascular patterns may be organized in this region in response to fetal stress.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractNineteen male subjects were given five daily injections of 17β-estradiol and circulating levels of estradiol (E2), testosterone (T), and gonadotropins were determined by radioimmunoassay before, during, and after the steroid course. Peak levels of E2attained during the 5 days of treatment ranged from 173–577 pg/ml. Four of seven normal adult men and one castrate man demonstrated suppression of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) with a subsequent rise in LH (positive feedback) while E2levels remained elevated. A rise in T was associated with the LH increment in the four normal men. Nine pre-, early, or midpubertal boys and two men with hypogonadotropic hypogonadism displayed only gonadotropin suppression after E2administration. The difference in LH response to estrogen (i.e., positive feedback) between the adult men with normal or elevated gonadotropin levels as compared with the endocrinologically normal boys is significant (P< 0.01).SpeculationPositive feedback between estrogen and LH is present in intact adult men, although the magnitude and consistency of this response is less than in women. Testosterone in men may act like progester-one in the female rhesus monkey to blunt the magnitude of the LH rise during estrogen administration. The potential for positive feedback appears to be a maturational event occurring during puberty in men as well as in women.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractGlycogen metabolism was studied in the isolated perfused liver of the monkey conceptus at 90% of gestation using anin siturecirculating perfusion system. Net uptake of glucose and galactose and the activities of the enzymes, glycogen synthetase and phosphorylase, were studied in response to varied perfusate composition. Synthetase activity was expressed as %1, the percentage of total synthetase activity in the active form. Perfusate glucose concentrations as high as 700 mg/100 ml did not lead to net glucose uptake or to an increase in the baseline %I synthetase (4 ± 1, mean ± SEM). In the presence of 300 mg/100 ml glucose, insulin at 10-7M increased %I to 8 ± 2, and galactose > 75 mg/100 ml increased %I to 8 ± 1. The combination of galactose, glucose, and insulin increased %I to 40 ± 5. With this latter combination, synthetase activity was proportional to perfusale glucose concentration above 100 mg/100 ml. Phosphorylase activity was diminished by either galactose or insulin, and phosphorylase activity was lowest in the group receiving galactose, glucose, and insulin. Galactose was taken up by all livers, but net glucose uptake was not observed under any condition; net hexose uptake was observed in perfusions with galactose. Glycogen levels did not vary significantly with varied perfusate composition during the 30-min perfusion periods.SpeculationWe speculate that galactose may be uniquely important for neonatal liver glycogen synthesis, and that its action is mediated through reciprocal changes in the activities of the enzymes, glycogen synthetase and phosphorylase. If liver glycogen is important for acute neonatal glucose homeostasis, then galactose may also be essential for maintaining circulating glucose concentration by ensuring glycogen synthesis during feeding.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID