ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

To determine the role of insulin clearance in the dawn phenomenon, we studied 10 adolescents with IDDM in comparison to 10 healthy, matched control sub-jects reported previously. In diabetics, metabolic clearance rate of insulin was calculated during i. v. infusion of insulin from 0100 to 0430 h and from 0430 to 0800 h (0.17 and 0.33 mU/kg/min, respectively), with a Harvard pump, while maintaining nocturnal euglycemia. In controls, met- abolic clearance rate of insulin was calculated from the prehepatic insulin secretion rate based on C-peptide levels. In diabetic and control subjects, plasma glucose, free in-sulin, and glucagon concentrations were similar and did not change during the dawn period. However, metabolic clearance rate of insulin increased during the dawn period in diabetic (9.42 ± 0.91 to 19.89 ± 1.52 mL/kg/min, p < 0.0001) and control subjects (4.87 ± 1.11 to 9.30 ± 1.50 mL/kg/min, p = 0.008). Plasma Cortisol and adrenocorti cotropic hormone levels increased and growth hormone (GH) decreased significantly during the dawn period. Diabetic adolescents had significantly higher plasma GH levels than control subjects throughout the night. We conclude the 1) increased insulin clearance is responsible for the dawn phenomenon in healthy and diabetic adolescents and 2) insulin resistance due to GH is an unlikely cause for the dawn phenomenon because diabetic subjects, despite higher GH levels, maintain plasma glucose levels similar to control subjects without requiring higher plasma free insulin concentrations.

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The effect of prolactin (PRL) on renal Na+K+-ATPase was investigated in 7-d-old neonatal rats. Animals were treated by bromocriptine (Br; a blocker of endogenous PRL secretion), and the enzyme activity was compared with that of untreated controls. Na+K+-ATPase was determined in renal sections in the medullary thick ascending limb of Henle's loop and in the distal tubule by cytochemistry. In the distal tubule, Na+K+-ATPase activity was significantly lower in Br-treated animals than in controls (330 ± 169 versus 558 ± 146 pmol inorganic phosphate/mm/h, respectively); values did not differ in the medullary thick ascending limb of Henle's loop between Br-treated and control animals (132 ± 74 versus 165 ± 113 pmol inorganic phosphate/mm/h, respectively). In vitro effects of PRL were investigated by determining the enzyme activity after incubation of renal sections from Brtreated and untreated animals with different concentrations of PRL. Results suggest that PRL may affect renal Na+K+-ATPase activity in the distal tubule in the neonatal period but do not support a major role of PRL in the enzyme maturation.

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Impaired production and delivery of neutrophils to the site of infection have been implicated in the increased susceptibility of the neonate to infection. Because granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) play critical roles in the production of neutrophils from marrow precursors, we assessed the ability of leukocytes from neonates and adults to produce GM-CSF, G-CSF, and, for comparison, macrophage colony-stimulating factor (M-CSF) after stimulation with concanavalin A ± phorbol myristate acetate [blood mononuclear cells (MC) and T lymphocytes] or lipopolysaccharide (monocytes). MC and monocytes from adult and neonatal subjects produced mRNA for GM-CSF, G-CSF, and M-CSF, whereas T cells produced only GM-CSF mRNA. Neonatal MC and T cells accumulated only −30% as much GM-CSF mRNA as did adult MC and T cells. In contrast, the accumulation of GM-CSF mRNA by neonatal and adult monocytes was similar. Neonatal MC also accumulated similar amounts of G-CSF mRNA and somewhat more M-CSF mRNA than did adult MC; results with monocytes were similar to those with MC. Results of colony-stimulating activity bioassays on supernatants from neonatal and adult MC stimulated with concanavalin A paralleled the mRNA results. Although the overall number of colonies generated using neonatal and adult supernatants was similar, neonatal MC supernatants generated significantly more (p < 0.05) monocyte-containing colonies (72 ±19 versus 46 ± 11), significantly fewer (p < 0.05) eosinophil-containing colonies (7 ± 6 versus 23 ± 13), and similar numbers of granulocyte-containing colonies (59 ± 23 versus 63 ± 11) compared with adult MC supernatants. Because GM-CSF is a major determinant of eosinophil production in these assays, these data suggested diminished amounts of GM- CSF in the neonatal culture supernatants. Similarly, GM- CSF concentrations in neonatal MC and T cell culture supernatants averaged 40 to 50% of the concentrations in adult culture supernatants as determined by ELISA (p < 0.01). Whether the modestly diminished GM-CSF production by neonatal T cells contributes t the observed deficiency of granulocyte production in neonates, which occurs when demand is increased in response to infection, remains to be determined.

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Dried blood spots are used for newborn screening because of ease of sample collection, handling, and shipment. DNA is stable and accessible in the filter paper matrix. Genotypic confirmation using initial specimens is demonstrated for a regional screening program. Seventy-five blinded samples underwent DNA analysis after Hb electrophoresis. DNA was microextracted from a 1/2-inch semicircle (25 $mUL whole blood equivalent), amplified, and analyzed by four different methods. Direct amplification without microextraction and automated sequencing from microextracted DNA also was performed. All four analyses agreed for the A and S alleles in 70 of 75 specimens. Three disagreements were clarified by the other semicircle from the original sample: two were due to polymerase chain reaction contamination and one to contamination of one of four analytical tests. Two would have required analysis of a second specimen, one because of polymerase chain reaction failure and the second because the patient had S/β-thalassemia. Direct amplification without microextraction was successful in an additional 77 of 78 specimens for analysis of the A, S, C, and E alleles. Automated direct sequencing from microextracted DNA was demonstrated for the A, S, and C alleles. Analysis of microextracted DNA from dried blood specimens for A and S alleles reduced the need for and costs of obtaining a second specimen for confirmation by 97%. Direct amplification without microextraction for analysis of A, S, and C alleles permits additional reduction in personnel time and costs. We have demonstrated that microextracted DNA is amenable to automated sequencing after asymmetric polymerase chain reaction. Direct genotypic confirmation can facilitate diagnosis and initiation of medical intervention.

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Group B streptococcus (GBS), a common neonatal gram-positive pathogen, causes similar pathophysiology in human newborns and neonatal animal models of sepsis. Animal models of GBS sepsis demonstrate a two-phase response: 1) an acute phase (<1 h) of increased pulmonary artery pressure (Ppa) and reduced arterial oxygen pressure (Pao2) that is associated with increased serum thromboxane B2(TxB2) and 2) a late phase (2–4 h) of persistently increased Ppaand reduced Pao2, reduced systemic arterial pressure, and progressive fall in cardiac output that is associated with increased serum TxB2, 6-keto-prostaglandin Fl$$ (6-keto-PGFi$$), and tumor necrosis factor-α (TNF$$). We hypothesized that pretreatment of piglets with both pentoxifylline (PTF), an inhibitor of TNF$$ production and activity, and indomethacin (INDO) would 1) inhibit GBS-induced TxB2, 6-keto-PGF1%, and TNF“ and 2) prevent both the acute- and late-phase physiologic responses of GBS sepsis. Combined PTF and INDO pretreatment of anesthetized, mechanically ventilated piglets infused with GBS (1.25 x 109colony forming units/ kg/h) for 4 h prevented GBS-induced increases in Ppa at 1 h (GBS+PTF+INDO: 1.8 $$ 0.07 kPa versus GBS alone: 4.7 ± 0.1 kPa) and markedly attenuated increases in Ppa at 4 h (GBS+PTF+INDO: 2.1 ± 0.1 kPa versus GBS alone: 4.4 ± 0.1 kPa). PTF+INDO treatment prevented GBS-induced reductions in both mixed venous oxygen pressure and Pao2at 1, 2, and 4 h (GBS+PTF+INDO: 11.5 ± 0.4 kPa versus GBS alone: 7.1 ± 0.4 kPa), and attenuated GBS-induced declines in cardiac output. PTF+INDO treatment significantly attenuated GBS-induced serum TNF$$ polypeptide levels (ELISA, pg/mL) at 4 h (GBS+PTF+INDO: 143 ± 45 versus GBS alone: 502 ± 147) and blocked GBS-induced increases in serum TxB2 and 6-keto-PGF1% (all levels < 10 pg/0.1 mL by RIA). INDO pretreatment alone prevented GBS-induced increases in serum TxB2and 6-keto-PGF1$$* levels but did not significantly inhibit GBS-induced TNF$$ production. INDO pretreatment alone did not attenuate GBS-induced increases in Ppa at 4 h, nor prevent late-phase reductions in both Pao2 and mixed venous oxygen pressure. PTF+INDO treatment of GBS sepsis in piglets is superior to treatment with INDO or PTF alone. Inhibition of both blood eicosanoid and TNF$$ production may provide adjunctive therapy for human newborns with sepsis and pulmonary hypertension.

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Undernutrition in human infants is associated with more prolonged episodes of diarrheal disease. Therefore, we tested the hypothesis that malnutrition prolongs the duration of Escherichia coli heat-stable enterotoxin-induced rat jejunal secretion. At weaning, rats were separated into two groups: malnourished rats were fed 50% of the previous day's intake of the fully fed control group. After approximately 2 wk of pair feeding, when malnourished rats weighed $$60$$ of the full fed control group, we measured the secretory response to heat-stable enterotoxin in ligated jejunal loops. Toxin-induced secretion was equal in both groups until 30 min incubation time, after which net secretion continued to increase in the malnourished group but decreased in the fully fed group. Jejunal brush border membranes prepared from malnourished and fully fed rats demonstrated similar heat-stable enterotoxin receptor density, avidity of binding and guanyl cyclase activation. In both groups, radiolabeled toxin injected into in situ jejunal loops was converted into an altered radioligand unable to bind to brush border membranes. However, in malnourished rats, there was both increased appearance of two additional radioligands that still retained their ability to bind to brush border membranes and persistence of biologically active unlabeled toxin as measured in the suckling mouse bioassay. Our studies demonstrate that reduced or delayed inactivation of heat-stable enterotoxin, with continued presence of active toxin species, may contribute to prolonged secretion in the jejunum of malnourished rats.

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Growth failure is a major complication of chronic hypoxemia, as seen in infants and children with cyanotic congenital heart disease. To determine whether chronic hypoxemia during infancy affects the gastrointestinal tract, we examined small intestinal growth and digestive enzyme activities in chronically hypoxemic newborn lambs and in age-matched controls. Chronic hypoxemia was produced by placing an inflatable occluder around the main pulmonary artery and performing a balloon atrial septostomy. Aortic oxygen saturation was reduced to 60− 74% for 2 wk, after which the small intestine was removed for analysis. During chronic hypoxemia, somatic growth rate was decreased to 60% of control (hypoxemic, 135 $$ 20 versus control, 216 $$ 26 g/d5Jp < 0.02). No differences in caloric intake were found (hypoxemic, 129 $$ 4 versus control, 128 $$ 4 kcal/kg/d). Chronic hypoxemia did not alter small intestinal growth, as measured by jejuno-ileal weight, jejuno-ileal length, mucosal weight, or mucosal protein or DNA contents. However, sp act of lactase, the principal disaccharidase of the infant lamb intestine, were significantly decreased (hypoxemic, 0.08 ± 0.01 versus control, 0.146 ± 0.03 units of enzyme activity/mg DNA, p < 0.05), as were the total small intestinal contents of lactase (hypoxemic, 61.7 ± 7.0 versus control, 120.6 ± 21.7 units of enzyme activity, p < 0.01). There also were decreases in specific and total activities of other digestive enzymes such as maltase, amino-oligopeptidase, and alkaline phosphatase in hypoxemic intestine that did not achieve statistical significance. In conclusion, chronic hypoxemia in infancy is associated with decreases in activities of intestinal lactase, which may result in diminished capacity for absorption of dietary carbohydrate. Alterations in intestinal function may contribute to growth failure associated with chronic hypoxemia.

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Histidine-rich glycoprotein (HRG) is a 74− kD glycoprotein, originally discovered in plasma, whichcontains an unusually large amount of histidine (13 mol$$) and proline (13 mol%). The specific functions of this protein remain unclear, although it binds (reversibly) transition metal ions such as Cu(II) and Zn(II) with high capacity (10–13 equivalent) and moderate to high affinity (kd = 0.2–10 $mUM). Because the bioavailability of Cu(II) and Zn(II) ions in human milk is high, we have used specific antibodies from polyclonal antisera directed against purified human plasma HRG to investigate whether this or a related protein is a component of human colostrum and(or) mature milk. Fresh human colostrum (d 1–3) and milk (d 4–120) were collected in the presence and absence of multiple protease inhibitors and EDTA. Immuno “dot” blot analyses and ELISA were developed; HRG was present in both colostrum (0.13–10 $mUg/mL) and mature milk (0.1–10 $mUg/mL). Unidentified components in colostrum and milk, however, were found to depress HRG antigenicity in these assays. Western transfer and immunoblots of denatured colostrum and milk samples analyzed by SDS-PAGE revealed the presence of an immunoreactive band at 74–78 kD, with other bands at 47 and 24 kD under both reducing and nonreducing conditions; smaller immunoreactive fragments (12–14 kD) were detected in some samples. We observed at least one additional band of immunoreactivity of greater molecular mass ($$110 kD) in colostrum under nonreducing conditions; we did not observe these bands in plasma samples. Immunoaffinity and Zn(II) affinity isolation of HRG from colostrum and milk resulted in the copurification of several associated proteins. N-terminal amino acid sequence analysis of the isolated 74-kD immunoreactive protein provided further evidence for identification as intact HRG; 13 of the first 15 residues were identical. These results demonstrate the presence of HRG, or a structurally related protein, in human colostrums and milk.

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

We studied the developmental changes in hepatic protein synthesis in suckling rats between postpartum d 1 and 28 and investigated the effect of fasting for 10 or 18 h on hepatic protein turnover at postpartum d 5, 10, 16, and 28. Fractional protein synthesis rates (Ks, $$/d) were measured in vivo using a flooding dose of l-[4–3H] phenylalanine. Although hepatic Ks and translation efficiency (protein synthesis/unit RNA) were significantly higher at postpartum d 28 than d 1, the pattern of change was biphasic: Ks and translational efficiency were higher at d 10 and 28 than at d 5 and 16. The largest increase in Ks and translational efficiency occurred during the period normally associated with weaning (between postpartum d 16 and 28). At all stages of development, the Ks and translational efficiency in fasted rats were significantly lower than those in control (fed) rats, although the relative decline in both measurements was largest at postpartum d 10. The absolute rates of hepatic protein synthesis declined to similar levels on d 5, 10, and 16 after 10 h of fasting and changed little after 18 h of fasting; this level was significantly higher at postpartum d 28. Our results suggest that postnatal development in suckling rats was marked by a biphasic pattern in the rates of hepatic protein synthesis, which increased during the neonatal and wea ning periods. The relative changes in the synthesis and loss of hepatic protein in response to fasting were greater during the neonatal than during the late suckling and weaning periods.

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID