摘要:

SummaryCarbohydrate metabolism was studied in 6 adult patients with phenylketonuria both on a low phenylalanine and an unrestricted institutional diet. Tolerance tests included PO glucose, PO phenylalanine, and combined glucose and phenylalanine loading. Glucose, insulin, pyruvate, lactate, and phenylalanine were sampled at 0, ½, 1, 2, 3, and 4 hr. Fasting glucose levels were normal as were mean glucose values after challenge. Basal insulin secretion, as well as insulin response, to glucose challenge and to combined phenylalanine and glucose loading appeared normal. Insulin response to phenylalanine alone, however, was lower than expected in the phenylketonuria patients. Both off and on low phenylalanine diet, blood pyruvate and lactate values were also normal. Thus, our data from blood did not show evidence of the abnormalities in glucose and pyruvate metabolism which have been proposed to occur in phenylketonuric patients but did suggest that the potency of phenylalanine as an insulin secretagogue is diminished by chronic hyperphenylalaninemia.SpeculationCarbohydrate metabolism following a glucose load and measured in whole blood appears normal in phenylketonuria. In contrast, the insulin response to a phenylalanine load appears decreased. Chronic hyperphenylalaninemia may produce a state of subsensitivity of the pancreas for the insulin response to an acute phenylalanine load.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

SummaryOf the four possible stereoisomers of isoleucine, only l‐alloisoleucine and l‐isoleucine were found by capillary gas chromatography in the plasma of two maple syrup urine disease (MSUD) patients, one with classical and one with variant MSUD. The relative plasma concentration ratios of l‐alloisoleucine/l‐isoleucine were 0.795 ± 0.025 (±95% confidence limits) and 0.637 ± 0.016 in the classical‐ and variant‐MSUD patients, respectively. The patients were also studied in the postabsorptive state with a 6‐hr continuous infusion of l‐[15N]leucine. In each patient plasma leucine15N enrichment approximated plateau after 150 min, and there was rapid appearance of [15N]isoleucine and [15N]alloisoleucine which were identical at plateau, although in the variant‐MSUD patient [15N]alloisoleucine enrichment did not equal that of [15N]isoleucine until 240 min of infusion. These results offer directin vivoevidence for the rapid equilibrium of plasma isoleucine and alloisoleucine through keto‐enol tautomerization of &agr;‐keto‐&bgr;‐methylvalerate.SpeculationInfusion of a15N‐labeled, branched‐chain amino acid with measurement of15N incorporation into the other branched‐chain amino acids may provide useful information about branched‐chain amino acid metabolism and offer a new approach to estimatingin vivobranched‐chain amino acid transferase activity.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

SummaryQuantitative determinations of cryoglobulins (IgG, IgA, IgM, and C3) were performed by a laser nephelometry microtechnique on 250 serum samples from a group of pediatric patients suspected of having immune complex‐mediated disorders. Approximately 50% of these samples were cryoglobulin positive. Patients with cryoglobulins were examined as three separate groups: systemic lupus erythematosus, presumptive autoimmune disorders, and chronic bacterial or viral infections. Nearly all of these patients have mixed cryoglobulins. The relation of cryoglobulinemia with serum hypocomplementemia and renal involvement was examined in a group of systemic lupus erythematosus patients. High levels of cryoglobulins were found in patients with hypocomplementemia and anti‐DNA antibodies without clinical evidence of nephritis. Highly significant correlations were observed between C1q binding activity, presence of cryoglobulins, and serum hypocomplementemia in systemic lupus erythematosus patients. Only 60% of the cryoglobulin positive samples had immune complex demonstrable by C1q binding. Cryoglobulin analysis using the laser nephelometry microtechnique permits screening of pediatric patients for the presence of immune complex, permits detection of low levels of cryoglobulins, allows quantitative determination of the specific immunoglobulin classes in the precipitate, and requires only a very small amount of blood suitable for the pediatric population.SpeculationCryoglobulins may represent circulating immune complex (IC) in diseases where IC‐mediated pathogenesis is implicated. In systemic lupus erythematosus, presence of anti‐DNA antibodies, C1q binding activity and hypocomplementemia was accompanied by elevated cryoglobulins. It is possible that in these patients, the presence of IC detected by C1q binding activity is reflected by elevated cryoglobulins. When considering autoimmune diseases in general, cryoglobulin analysis via laser nephelometry may be more sensitive than C1q binding in detecting IC, some of which may not bind complement. This technique could easily be utilized as a screening, diagnostic, and perhaps prognostic tool for children with autoimmune diseases.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

SummaryThe experiments reported here illustrate a few of the factors apart from genes which can influence hormone‐responsive generation of cyclic adenosine 3′:5′‐monophosphate in human fibroblasts. For both normal and cystic fibrosis fibroblasts, the isoproterenol stimulation ratio was maximal 2 to 3 days after subculture and declined thereafter; prostaglandin E1stimulation ratio was maximal 7 to 10 days after subculture, Cells dislodged from the plate by either scraping or trypsinization had reduced isoproterenol or prostaglandin E1stimulation ratios compared to cells studiedin situ.Fibroblasts from healthy controls and cystic fibrosis patients plated simultaneously and grown in three different culture conditions responded similarly to the change in growth conditions. Addition to the incubation medium of polyamines, calcium, magnesium, or guanosine triphosphate did not alter the stimulation ratios for isoproterenol or prostaglandin E1. Repeated measures analysis indicates that cellular content of cyclic adenosine 3′:5′‐monophosphate is not a reliable measure for comparing cell lines; isoproterenol stimulation ratio is a reliable measure, but there is large variation from cell line to cell line. Isoproterenol stimulation ratio was the same for normal and cystic fibrosis fibroblasts in each of the three culture conditions tested at both three and ten days after subculture.SpeculationBecause of the unexplained day‐to‐day variability in cellular cyclic adenosine 3′:5′‐monophosphate content, the multiple exogenous influences on hormone‐responsive cyclic adenosine 3′:5′‐monophosphate, and the potential limitations of studying fibroblasts only on their support so as not to perturb the membrane‐associated receptor adenylate cyclase system, the cultured skin fibroblast may not be the optimal system for population studies of adrenergic‐responsive adenylate cyclase in human disease.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

SummaryCirculating arginine vasopressin (AVP) and plasma renin activity responses to furosemide (2 mg/kg) and acute hypertonic saline (10 mEq/kg) were studied in the fetal lamb from 100 days gestation to term. The baseline to peak plasma AVP response (&Dgr;3.7 ± 1.2 uU/ml) and area under the response curve (209 ± 57 uU/ml/65 min) in the fetal lambs > 123 days were greater than in those <106 days gestation (&Dgr;1.8 ± 1.1 and (171 ± 61, respectively),P<0.02. The plasma renin activity/AVP ratio after furosemide was similar in the two gestational groups.The log plasma AVP responses corrected for rise in plasma osmolality (0.090 ± .01 uU/ml) 30 min after infusion, and the area under the response curve (253 ± 49 uU/ml/30 min) was greater (P< 0.02) in the fetal lambs > 120 days than in those under 115 days gestation (.035 ± 0.01 and 88 ± 29, respectively),P< 0.02. These results confirm that the fetal lamb responds to an osmotic stimulus with increased plasma AVP levels and documents that this response significantly matures during the last trimester of gestation. The fetal lamb also manifests a hypothalamus‐posterior pituitary AVP response to furosemide that is proportional to the maturing renal renin response.SpeculationThere is a significant maturational plasma arginine vasopressin response to acute hypertonic saline and furosemide in the fetal lamb during the last trimester of gestation.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

SummaryLung lavage samples were obtained in control and reserpine‐treated rats after they were given 12 daily IP injections (10 mg) of either isoproterenol or pilocarpine. Similar samples were obtained from other control and reserpine‐treated animals that received no secretagogue for 12 days. In the latter group, the total protein, lipid, and carbohydrate contents of the lavage samples were similar in control and reserpine‐treated rats. Chronic isoproterenol administration caused a 2.5‐fold increase in the lipid content, but no change in the protein or carbohydrate contents, of pulmonary lavage samples of control rats. In reserpine‐treated rats, however, the same isoproterenol treatment caused a 2.6‐, 6.0‐, and 1.9‐fold increase, respectively, in the protein, lipid, and carbohydrate contents of lavage samples. Chronic treatment with pilocarpine resulted in a 2.6‐, 3.3‐, and 1.9‐fold increase in the protein, lipid, and carbohydrate contents of control samples and a 12.5‐, 5.6‐, and 9.3‐fold increase in the same components of lavage samples from reserpine‐treated rats. The increase in total lipid content observed in control and reserpine‐treated rats after chronic isoproterenol administration and in control rats after chronic pilocarpine treatment was not accompanied by changes in the percent distribution of the various lipid fractions. In reserpine‐treated rats receiving pilocarpine for 12 days, however, the increased lipid content was due primarily to a significant increase in the phospholipid content, specifically phosphatidylcholine. Although the increased carbohydrate content observed in lavage samples of reserpine‐treated rats after chronic isoproterenol administration or in control rats after pilocarpine administration was not associated with changes in the percentage of distribution of the various sugar fractions, the increase induced by chronic pilocarpine treatment in reserpine‐treated animals was accompanied by increases in the fucose, galactose, and sialic acid contents. It is concluded that: (1) previous reserpine administration enhances the secretion of glycoprotein in the rat airways, particularly in response to long‐term pilocarpine treatment; (2) it also results in an increased content of lipids, particularly the phospholipid phosphatidylcho‐line; (3) this effect is no longer evident, however, 13 days after cessation of reserpine injections. These alterations in respiratory tract secretions of reserpine‐treated rats resemble those observed in cystic fibrosis and, in conjunction with other exocrine gland changes, suggest that this proposed model may be used to elucidate pathogenetic mechanisms in cystic fibrosis.SpeculationThe animal model for cystic fibrosis developed by chronic reserpine administration to rats has been shown to have significant elevations in the glycoprotein and lipid content of pulmonary lavage samples which were further enhanced when reserpine treatment was followed by acute pilocarpine stimulation. The present study has shown that chronic pilocarpine administration after reserpine pretreatment dramatically increased the glycoprotein content in pulmonary lavage samples and that the effect produced by chronic isoproterenol administration on lavage glycoprotein composition, although increased, was less marked. Both pilocarpine and isoproterenol caused increases in lavage lipids, but only pilocarpine significantly augmented the phospholipid fraction. We speculate that the hypersecretion of pulmonary glycoproteins and the increase in airway lipids exhibited by reserpine‐treated rats when challenged chronically with specific neuropharmacologic agents makes this model an excellent tool for further studies directed towards the elucidation of the pulmonary mucus hypersecretion seen in cystic fibrosis.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

SummaryA low‐molecular‐weight zinc‐binding ligand from human milk has been isolated and characterized. The ligand was isolated by chromatography on Dowex 50, Dowex 1, and Sephadex G‐15 equilibrated with 0.153 mM Zn(NO3)2. Mass spectroscopy, thin‐layer chromatography, and infrared spectroscopy proved that the zinc‐binding ligand isolated by this method from human milk is pyridine‐2‐carboxylic acid, commonly known as picolinic acid. The concentration of picolinic acid in human milk was 308 &mgr;M, the concentration in one brand of processed cow's milk was 20 &mgr;M, but picolinic acid was undetectable in a second brand of cow's milk and in four different infant formulas. Weanling rats fed supplemental picolinic acid absorbed significantly more dietary zinc and gained significantly more weight than rats fed an unsupplemented diet. The results suggest that the high bioavailability of zinc in human milk results from the presence of picolinic acid, a bidentate chelating ligand which facilitates zinc absorption from the intestine.SpeculationThe high bioavailability of zinc in human milk results from the presence of picolinic acid, a bidentate chelating ligand which facilitates zinc absorption from the intestine.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

SummaryMyocardial chemical sympathectomy was achieved by daily SC injection of 100 &mgr;g/g body weight of 6‐OH‐dopamine to each of 239 Holtzman newborn rat pups for the first seven days of life. Effective sympathectomy was verified by identifying a decrease in ventricular myocardial norepinephrine concentrations to 31% ± 12 S.E. of control at 20 days of age. Activity of DNA polymerase was used to indicate the extent of myocardial cell division.Beginning at eight days of age, DNA polymerase activity was increased in the sympathectomized pups relative to control. The DNA polymerase activity was highest relative to control at 16 days (235% ± 31 S.E.) and remained elevated beyond 20 days (188% ± 30 of control). The DNA polymerase data was analyzed by covariance and was significantly greater in the 6‐OH‐dopamine rat pups (P< 0.001).SpeculationMyocardial cell division continues for 10 to 14 days after birth in the newborn animal of several species, and the cell division then ceases by an unknown mechanism. Our findings are consistent with the hypothesis that this postnatal decrease in myocardial cell division is related to the development of cardiac sympathetic nerve ingrowth. Because nerve ingrowth was inhibited after 6‐OH‐dopamine and increased myocardial cell division occurred, it appears that sympathetic ingrowth indeed may play a key role in affecting myocardial cell division in the newborn animal.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

SummaryA child diagnosed at birth as deficient in red blood cell adenosine deaminase (ADA) but with substantial residual lymphocyte ADA has been evaluated for two and one‐half years. The only immunologic abnormality observed was hypogammaglobulinemia during the fifth month of life. This was unexpected because children with total ADA deficiency either have severe combined immunodeficiency or selectively greater impairment of cellular than humoral immunity. The absence of severe combined immunodeficiency in this child was associated with normal lymphocyte content of ATP, dATP, and cyclic 3′5′‐adenosine monophosphate, potentially toxic metabolites which are elevated in ADA‐deficient immunodeficient children.SpeculationPartial deficiency of lymphocyte adenosine deaminase, although sufficient for cell‐mediated immune function, may exaggerate physiologic conditions that favor decreased immunoglobulin synthesis. The substance(s) responsible for this effect are probably adenosine metabolites which are of undetermined nature.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID