Calcipotriol toxicity in a dog

The article describes the objectives and design of a prospective study of the prevalence, incidence and course of psychiatric disorders in a representative sample of non-institutionalized Dutch adults. A total of 7146 men and women aged 18-64, contacted through a multistage sample of municipalities and households, were interviewed at home in 1996. The primary diagnostic instrument was the CIDI, which determines the lifetime occurrence of DSM-III-R disorders. The disorders included were: mood disorders, anxiety disorders, eating disorders, schizophrenia and other non-affective psychotic disorders, and dependence and abuse of psychoactive substances. Follow-up measurements in the same sample were scheduled at 12 and 36 months. The net response to the first measurement was 69.7%. Poststratification weightings were applied for gender, age, marital status and degree of urbanization. Limitations and advantages of the study design are discussed. Findings are reported elsewhere in this issue.     

Biochemical evidence for pathogenicity of rhodopsin kinase mutations correlated with the oguchi form of congenital stationary night blindness

Rhodopsin kinase (RK), a rod photoreceptor cytosolic enzyme, plays a key role in the normal deactivation and recovery of the photoreceptor after exposure to light. To date, three different mutations in the RK locus have been associated with Oguchi disease, an autosomal recessive form of stationary night blindness in man characterized in part by delayed photoreceptor recovery [Yamamoto, S. , Sippel, K. C., Berson, E. L. & Dryja, T. P. (1997) Nat. Genet. 15, 175-178]. Two of the mutations involve exon 5, and the remaining mutation occurs in exon 7. Known exon 5 mutations include the deletion of the entire exon sequence [HRK(X5 del)] and a missense change leading to a Val380Asp substitution in the encoded product (HRKV380D). The mutation in exon 7 is a 4-bp deletion in codon 536 leading to premature termination of the encoded polypeptide [HRKS536(4-bp del)]. To provide biochemical evidence for pathogenicity of these mutations, wild-type human rhodopsin kinase (HRK) and mutant forms HRKV380D and HRKS536(4-bp del) were expressed in COS7 cells and their activities were compared. Wild-type HRK catalyzed light-dependent phosphorylation of rhodopsin efficiently. In contrast, both mutant proteins were markedly deficient in catalytic activity with HRKV380D showing virtually no detectible activity and HRKS536(4-bp del) only minimal light-dependent activity. These results provide biochemical evidence to support the pathogenicity of the RK mutations in man.     

Uninterrupted translation through putative 12-nucleotide coding gap in sequence of carA: business as usual

Previous work of others reported an untranslated stretch of 12 nucleotides in the 5' coding sequence of carA from Pseudomonas aeruginosa. However, N-terminal protein sequencing of carA-lacZ translational fusions shows that these 12 nucleotides are normally translated in a continuous triplet manner, both in P. aeruginosa and in Escherichia coli.     

Cricoid pressure: are two hands better than one?

A two-year-old, neutered male Labrador retriever was anesthetized with intravenous propofol for bronchoscopy to remove a bronchial foreign body. The dog previously had been diagnosed with idiopathic epilepsy. During anesthetic recovery, the dog exhibited excitatory movements characterized by forelimb extensor rigidity, opisthotonos, generalized tremors, paddling, horizontal nystagmus, and facial twitching. Intravenous administration of pentobarbital temporarily stopped the motor activity. The excitatory movements persisted for 20 hours. The dog went on to recover completely, although he remained an epileptic, having one brief, generalized grand mal seizure every three-to-four months.     

Mature T cell reactivity altered by peptide agonist that induces positive selection

Recent studies have investigated how defined peptides influence T cell development. Using a T cell receptor-transgenic beta2-microglobulin-deficient model, we have examined T cell maturation in fetal thymic organ cultures in the presence of various peptides containing single-alanine substitutions of the strong peptide agonist, p33. Cocultivation with the peptide A4Y, which contains an altered T cell contact residue, resulted in efficient positive selection. Several in vitro assays demonstrated that A4Y was a moderate agonist relative to p33. Although A4Y promoted positive selection over a wide concentration range, high doses of this peptide could not induce clonal deletion. Thymocytes maturing in the presence of A4Y were no longer able to respond to A4Y, but could proliferate against p33. These studies demonstrate that (a) peptides that induce efficient positive selection at high concentrations are not exclusively antagonists; (b) some agonists do not promote clonal deletion; (c) positive selection requires a unique T cell receptor-peptide-major histocompatibility complex interaction; and (d) interactions with selecting peptides during T cell ontogeny may define the functional reactivity of mature T cells.