Showing papers by "Hospital for Sick Children published in 1984"

The management and long term outcome of organic acidaemias

Abstract: We review the outcome of patients with maple syrup urine disease (14 classical patients and three variants), biotinidase deficiency (two patients) and non-cofactor-responsive variants of methylmalonic acidaemia (eight patients), propionic acidaemia (eight patients) and isolated 3-methylcrotonyl CoA carboxylase deficiency (three patients). Their survival, growth, intellectual development and other clinical problems are analysed. With the exception of isolated 3-methylcrotonyl CoA carboxylase deficiency the outcome of patients with disorders that are not cofactor responsive is disappointing. Twelve patients have died (five maple syrup urine disease, two methylmalonic acidaemia, five propionic acidaemia) and many of the survivors are developmentally retarded. The outlook is worst for patients with propionic acidaemia presenting in the neonatal period but a good outcome is possible for patients with maple syrup urine disease if the diagnosis is made early.

Interferon-induced 2-5A synthetase activity in human peripheral blood mononuclear cells after immunization with influenza virus and rubella virus vaccines.

Abstract: The interferon-induced enzyme 2-5A synthetase can be a sensitive indicator of activation of the human interferon system during viral infection or interferon therapy. To determine the response of the human interferon system to viral antigens, the level of 2-5A synthetase activity was monitored in peripheral blood mononuclear cells of healthy adults before and after immunization with influenza or rubella virus vaccine. The influenza virus-vaccinated individuals demonstrated increases in enzyme activity on days 1 and 11 in vivo, whereas those vaccinated with rubella virus vaccine showed an increase only on day 11. The difference in the day 1 in vivo 2-5A synthetase response in the two vaccinated groups could be demonstrated by in vitro incubations of peripheral blood mononuclear cells isolated approximately 90 days postvaccination with the two vaccines. The day 11 increase of enzyme activity in the rubella virus group showed a positive correlation with an increase in serum antibody titer, suggesting activation of the interferon system during antibody production in vivo after human exposure to virus antigens. The demonstration of increased 2-5A synthetase activity at specific times postimmunization in this investigation indicates that the interferon system is involved in the human in vivo response to virus vaccination.

Intermolecular Hydrogen Bonding between Membrane Lipids

Abstract: Biological membranes contain a great variety of lipids with different hydrocarbon chains, polar groups, backbone structure (glycerol or sphin-gosine), type of chemical linkage (ester or ether) of the hydrocarbon chains to glycerol, as well as other less common variations. This suggests that lipids must have some functions more specialized than maintenance of a bilayer to enclose the cell contents and of proper fluidity to allow dynamic protein function. Studies of the physical properties and phase behavior of lipids have shown that lipids can also play dynamic roles and can respond to changes in their environment by undergoing phase transitions, alterations in lipid— lipid and lipid—protein interactions, and by release or uptake of cations or protons. Several recent reviews have attempted to explain the special properties of different lipids and emphasized their dynamic organization and function (Trauble et al., 1976; Eibl, 1977; Seelig, 1978; Cullis and de Kruijff, 1979; Eibl and Woolley, 1979; Hauser and Phillips, 1979; Nagle, 1980; Barenholz and Thompson, 1980; Israelachvili et al., 1980; Boggs, 1980).

Method for coupling a hydrocarbon containing molecular species

Abstract: The present invention relates to a method for covalently coupling two molecular species and to the product of such coupling. The method has particular application to the binding of hydrocarbon containing ligands to a support matrix as may be required in, for example, affinity chromatography.

Insulin Delivery at Variable Rates from a Controlled Release Micropump

Abstract: A controlled release micropump (CRM) has been shown to be functional after implantation, without a catheter, in pancreatectomized dogs. Basal delivery is provided by diffusion through a thin hydrophilic membrane due to a concentration difference driving force. Augmented delivery is achieved by repeated compression of a foam disk by a piston which is the core of a solenoid wrapped around the barrel of the CRM. The device including reservoir weighs 110 g and consumes power only for augmented delivery, The CRM was implanted for intraperitoneal delivery, without a catheter, with a SILASTIC skirt assembly to secure the pump outlet to the inside of the peritoneal wall while the remainder of the pump was sutured to the abdominal muscles; tissue compatibility was acceptable. Augmented delivery for 1 hour was able to decrease the blood glucose level from 500 mg/dL to < 100 mg/dL two hours later, in fasting animals. However, extensive insulin aggregation with the conventional U100 insulin solution (Insulin Toronto) prevented the maintenance of this function without flushing the reservoir. This problem appears to have been relieved by the use of Hoechst insulin which contains a surfactant to prevent aggregation. With Hoechst insulin (HOE 21 PS) in a fresh implant, basal delivery alone resulted in the expected normalization of glucose levels after a meal was absorbed. This performance was maintained for 3-4 days without flushing the reservoir or other evidence of aggregation. Although much remains to be clarified (e.g., tissue reaction, reproducibility, time lags), the controlled release micropump may prove to have significant advantages over other devices intended to maintain normoglycemia sufficient to prevent the degenerative sequelae of diabetes.

In vitro hyporeactivity to α-interferon in children with severe combined immunodeficiency disease

Abstract: Interferon (IFN) treatment of peripheral blood mononuclear cells from seven children with severe combined immunodeficiency (SCID) failed, with one exception, to induce the IFN-dependent enzyme, 2-5A synthetase or enhance natural killer cell activity. In one patient this hyporeactivity was demonstrated in both T cell enriched and T cell depleted lymphocyte preparations. These results may reflect the absence of an IFN reactive lymphocyte subpopulation or of the IFN receptor. This defect in SCID patients may be partly responsible for their increased susceptibility to viral infections and may contribute to the regulatory imbalances in T lymphocyte subpopulations.

Problems in Diagnosis and Treatment of Adenine and Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency

Abstract: Adenine (APRT) and hypoxanthine-guanine (HGPRT) phosphoribosyltransferase deficiency were originally identified in children.1,2 The spectrum of manifestations in both is broad with similarities, but also important differences. Both are asociated with urinary calculi and can cause severe renal damage.1,2 Severe neurological problems are also found in complete HGPRT deficiency 1 but have not been noted in APRT deficiency. We have investigated 2 children presenting in renal failure that emphasise the problems of diagnosis and treatment of these 2 deficiencies and the particular difficulties encountered in the presence of impaired renal function.

The host defense system in the human newborn: the role of interferon and the natural killer cell

Abstract: The human newborn is particularly susceptible to infections in the neonatal period, due in part to the immaturity and naive state of the immune system. The role of interferon and natural killer cells in host defense in this age group is poorly defined. We have studied natural killer cells and the activation of the interferon system in cord blood. Most newborns (75%) had low natural killer cell activity, and this was unrelated to levels of the intracellular interferon-associated enzyme, 2'-5' oligoadenylate synthetase (2-5A synthetase). Newborn cells responded to interferon in vitro with an increase in natural killer activity, suggesting that this low natural killer cell activity is the result of fewer numbers of effector cells rather than a functional immaturity. Circulating serum interferon was detected in greater than 50% of maternal samples tested; however, this did not correlate with 2-5A synthetase levels in maternal or the corresponding cord blood mononuclear cells. Natural killer cell activity was low in the newborn in spite of activation of the interferon system in 39% of these individuals. This may be an important factor in susceptibility to infections in this period.

Serum lipase as a measurement of pancreatic function in cystic fibrosis

Abstract: A highly sensitive and specific ELISA immunoassay capable of measuring serum pancreatic lipase (S.Lip) has been developed. We assessed the usefulness of S.Lip for monitoring pancreatic function in CF. S.Lip was measured in 133 CF pts, 86 with steatorrhea (CFPI), 47 without steatorrhea (CFPS) and 83 controls. Ages are shown in the table. * S.Lip: μg/L. (mean ± SEM).

Purine metabolism in intact cells from a purine nucleoside phosphorylase deficient child.

Abstract: Deficiencies of two subsequent enzymes in the purine degradation pathway, Adenosine Deaminase (ADA) and Purine Nucleoside Phosphorylase (PNP), result in immunodeficiency in children (1–3). PNP deficient patients accumulate large amounts of all four PNP substrates, inosine, deoxyinosine, guanosine and deoxyguanosine in their plasma and urine (4,5). Moreover, the total urinary purine excretion by PNP deficient patients is several fold higher than the equivalent uric acid excretion by normal children (4,5). This observation indicates that the purine salvage pathway in humans is remarkably active and that PNP does not serve merely as a degrading enzyme, but it may also play a role in the reutilization of purines. The tissue(s) responsible for reutilization of purine has not been identified. It has been suggested that purine reutilization represents a means by which purines are transported from the liver a tissue with active purine de novo biosynthesis, to be reutilized by peripheral tissue(s). Alternatively, it may be that purine reutilization is mainly an intracellular process since most tissues have both purine de novo and purine salvage pathways.