The renal handling of delta-aminolevulinic acid in normal and lead-poisoning rabbits

A radioimmunoassay (RIA) procedure has been developed for measurement of testosterone in male plasma after ether:chloroform (4:1) extraction of the plasma sample without resorting to chromatography. The highly specific anti-testosterone serum was generated from both rabbits and sheep immunized with 15beta-carboxyethylmercapto-testosterone-BSA conjugate. The synthesis of 15beta-carboxyethylmercaptotestosterone and the preparation of its BSA conjugate are described. The high affinity (Ka=2.38 X 10(9) liters/mole) antiserum binds 50% of 50 picograms of tritiated testosterone at working dilutions of 1:100,000 to 1:200,000. Both 5alpha and 5beta-dihydrotestosterone compounds exhibited less than 2% cross-reaction. The only other steroids that showed minor cross-reaction were 11beta-hydroxytestosterone (3.8%), progesterone (2.1%), corticosterone (1.6%), and deoxycorticosterone (7.7%).     

Spinning on its axes: DSM and the social construction of psychiatric diagnosis

Through a critical examination of the psychiatric profession's heavy reliance on the Diagnostic and Statistical Manual of Mental Disorders, the authors explore the central role of diagnosis in the theory and practice of psychiatry. The set of beliefs that have guided the psychiatric profession since the creation of DSM-III are viewed as being tied to the new extension of the biopsychiatric medical model. From a sociological perspective, the authors address the issue of psychiatric nosology with reference to practice styles and professional dominance, and consider the impact of DSM's intrinsic social biases both within and outside psychiatry's traditionally drawn boundaries. They conclude that working soley within the confines of a medical framework of diagnosis, with little attention to the wider social and cultural contexts that should surround diagnostic practice, psychiatry will be unable to understand and explain the changing needs of its clientele.     

House staff supervision, workload, and experience in the neonatal intensive care unit: results of a national survey

One hundred fifty-nine pediatric chief residents were surveyed regarding characteristics of the neonatal intensive care unit rotation for house staff at their institution. We documented substantial interinstitution variability in house staff NICU rotations in terms of number of rotations, and the workload and supervision of house staff.     

Opioid modulation of extracellular signal-regulated protein kinase activity is ras-dependent and involves Gbetagamma subunits

Although it is well-established that G protein-coupled receptor signaling systems can network with those of tyrosine kinase receptors by several mechanisms, the point(s) of convergence of the two pathways remains largely undelineated, particularly for opioids. Here we demonstrate that opioid agonists modulate the activity of the extracellular signal-regulated protein kinase (ERK) in African green monkey kidney COS-7 cells transiently cotransfected with mu-, delta-, or kappa-opioid receptors and ERK1- or ERK2-containing plasmids. Recombinant proteins in transfected cells were characterized by binding assay or immunoblotting. On treatment with corresponding mu- ([D-Ala2,Me-Phe4,Gly-ol5]enkephalin)-, delta- ([D-Pen2,D-Pen5]enkephalin)-, or kappa- (U69593)-selective opioid agonists, a dose-dependent, rapid stimulation of ERK1 and ERK2 activity was observed. This activation was inhibited by specific antagonists, suggesting the involvement of opioid receptors. Pretreatment of cells with pertussis toxin abolished ERK1 and ERK2 activation by agonists. Cotransfection of cells with dominant negative mutant N17-Ras or with a betagamma scavenger, CD8- beta-adrenergic receptor kinase-C, suppressed opioid stimulation of ERK1 and ERK2. When epidermal growth factor was used to activate ERK1, chronic (>2-h) opioid agonist treatment resulted in attenuation of the stimulation by the growth factor. This inhibition was blocked by the corresponding antagonists and CD8- beta-adrenergic receptor kinase-C cotransfection. These results suggest a mechanism involving Ras and betagamma subunits of Gi/o proteins in opioid agonist activation of ERK1 and ERK2, as well as opioid modulation of epidermal growth factor-induced ERK activity.     

S-2-amino-5-azolylpentanoic acids related to L-ornithine as inhibitors of the isoforms of nitric oxide synthase (NOS)

To characterize the importance of a highly conserved region of the class II beta chain, we introduced an amino acid substitution that is predicted to eliminate a hydrogen bond formed between the class II molecule and peptide. We expressed the mutated beta chain with a wild-type alpha chain in a murine L cell by gene transfection. The mutant class II molecule (81betaH-) assembles normally in the endoplasmic reticulum and transits the Golgi complex. When invariant chain (Ii) is coexpressed with 81betaH-, the class II-Ii complex is degraded in the endosomes. Expression of 81betaH- in the absence of Ii results in a cell surface expressed molecule that is susceptible to proteolysis, a condition reversed by incubation with a peptide known to associate with 81betaH-. We propose that 81betaH- is protease sensitive because it is unable to productively associate with most peptides, including classII-associated invariant chain peptides. This model is supported by our data demonstrating protease sensitivity of peptide-free wild-type I-Ad molecules. Collectively, our results suggest both that the hydrogen bonds formed between the class II molecule and peptide are important for the integrity and stability of the complex, and that empty class II molecules are protease sensitive and degraded in endosomes. One function of DM may be to insure continuous groove occupancy of the class II molecule.     

Surgical decisions in chronic angle-closure glaucoma

A retrospective study of 57 eyes with chronic angle-closure showed that eyes with visual field loss are less likely to be improved by iridectomy than those without visual field loss in the presence of visual field loss, trabeculectomy achieved more satisfactory control of glaucoma than did iridectomy, and there was no noticeable difference in surgical complications between iridectomy and trabeculectomy in this small series. It is suggested that iridectomy is indicated for most cases of chronic angle closure without visual field loss, especially if the pressure is medically controllable. In the presence of visual field loss, iridectomy is usually a wise choice if medical control is easily achieved preoperatively. However, trabeculectomy might be the best choice in most patients with visual field loss and medically uncontrolled pressure, regardless of the gonioscopic findings.