The metabolism of IgE. Studies in normal individuals and in a patient with IgE myeloma

IgE metabolic turnover studies with purified radioiodinated IgE were performed in normal individuals and in a patient with IgE myeloma. The validity of the turnover studies was established in several ways, including comparisons of radioiodinated IgE turnover with the turnover of endogenously labeled 14C-IgE and with the turnover of infused unlabeled IgE in a patient with hypogammaglobulinemia. The geometric mean serum IgE concentration in 73 normal adults was 96 ng/ml with a 68% confidence interval of 24 to 386 ng/ml. Metabolic turnover studies in 10 control individuals disclosed a geometric mean total circulating IgE of 4.1 mug/kg, a mean percentage of the total exchangeable IgE in the intravascular space of 41%, a mean half-time of survival of IgE of 2.7 days, a mean fractional catabolic rate of 94% of intravascular pool per day, and a geometric mean synthetic rate of 3.8 mug/kg/day. IgE has the lowest synthetic rate and highest fractional catabolic rate of the five major classes of immunoglobulin molecules. In contrast to these normal values, a patient with IgE myeloma had a serum IgE comcentration of 42 mg/ml, a total circulating IgE of 1.7 g/kg, and a synthetic rate of 270 mg/kg/day. Furthermore, although the synthetic rate was vastly increased, the survival time was prolonged and the fractional catabolic rate was decreased to 5.1 days and 16 to 22% of the intravascular pool per day, respectively. These data are compatible with the concept that IgE is catabolized in part by a mechanism common to all immunoglobulin classes and in part by a unique mechanism not available to other immunoglobulins. At very high IgE serum concentrations, such as those encountered in patients with IgE myeloma, the unique mechanism would be saturated and only the catabolic pathways available to all immunoglobulins would be available to IgE.     

Driving Votrax SCOI with microcomputers

The Votrax SCOI is a single-chip speech synthesizer with potential applications in areas such as automatic weather reporting, telecommunications and learning aids. The pinout of the chip is described briefly, and the constraints to be satisfied when interfacing it to a microcomputer for realtime speech synthesis are examined in depth. The operation of the driving software is outlined step by step, including text-to-phoneme conversion.     

Mutations in the carboxyl terminus of the agouti protein decrease agouti inhibition of ligand binding to the melanocortin receptors

Several mutations that cause ectopic expression of the agouti gene result in obesity, hyperinsulinemia, and yellow coat color. A candidate pathway for agouti induced obesity and hyperinsulinemia is through altered signaling by melanocortin receptors, as agouti normally regulates coat coloration through antagonism of melanocortin receptor 1. Furthermore, melanocortin peptides mediate functions including steroidogenesis, lipolysis, and thermoregulation. We report apparent inhibition dissociation constants for mouse and human agouti protein inhibition of ligand binding to the melanocortin receptors, to determine which of these receptors might be involved in agouti induced diabetes. The similarity in the apparent K(I) values for agouti inhibition of ligand binding to the brain melanocortin receptors 3 and 4 (mouse: K(I) app = 190 +/- 74 and 54 +/- 18 nM; human: K(I) app = 140 +/- 56 and 70 +/- 18 nM, respectively) suggests that the MC3-R is a potential candidate for a receptor mediating the effects of agouti protein overexpression. Agouti residues important for melanocortin receptor inhibition were identified through the analysis of deletion constructs and site-specific variants. Val83 is important for inhibition of binding to MC1-R (K(I) app for Val83Ala agouti increased 13-fold relative to wild-type protein). Arg85, Pro86, and Pro89 are important for selective inhibition of binding between MC1-R and MC3-R and MC4-R as their apparent K(I) values are essentially unchanged at MC1-R, while they have increased 6-10-fold relative to wild-type protein at MC3-R and MC4-R.     

Fatal rhino-orbital-cerebral zygomycosis

Rhinocerebral zygomycosis is usually an aggressive, fulminant and, at times, fatal disease most often affecting poorly controlled diabetics of all ages. We report the case of a 13-month-old white boy, a previously undiagnosed diabetic. He came to our hospital with recurrent epistaxis, decreasing consciousness, and a small visible infection at the inner canthus of the left eye. Initial evaluation revealed that the patient was in diabetic ketoacidosis. Despite aggressive medical and surgical treatment, his condition deteriorated rapidly, including the development of diabetes insipidus, and he died 4 days after admission. At autopsy, he was found to have fungal cerebritis (Rhizopus) with multiple areas of infarction and massive cerebral edema.     

Microsurgical replantation of the main segments of the extremities

Computerizing an organization's policies and guidelines is difficult but rewarding. The assessment, planning, implementation, and evaluation of converting all paper policies and procedures into a computerized system are outlined, with particular focus on organizing guidelines according to the Joint Commission on Accreditation of Healthcare Organization's (JCAHO) functional standards.