The Canadian Epilepsy Database and Registry

Epilepsy encompasses medical, psychological, social and demographic factors which are best studied in large populations. The Canadian Epilepsy Database and Registry (CEDAR) is a comprehensive English language, multicentre epilepsy database which has been developed to study the impact of these and other factors on epilepsy in Canada. In addition, it can be used locally in the clinic for office record keeping, automated printout of a referral letter or graphing seizures and other data over time. The data in CEDAR are similar to what is found in the patient's chart. There are 20 participating centres across Canada which have entered data on over 8000 adult and pediatric epilepsy patients. The information in CEDAR will be available for research purposes to centres entering data as well as to academic researchers, the pharmaceutical industry and government agencies.     

An interpersonal perspective: The analyst's unwitting participation in the patient's change.

Comments on the analysis of P. A. Dewald's (1972) patient and suggests that Dewald's technique is an example of 1-person psychology. The analyst believes he/she is observing the pure culture of the patient's projection of intrapsychic, drive-based material. The author attempts to bring a 2-person, participant-observation, perspectivist model to the clinical interaction between Dewald and his patient. A variety of ways in which Dewald unwittingly participated in the patient's transference to him are outlined. It is argued that these unidentified countertransference enactments clearly influenced the patient and were not sufficiently addressed in the analysis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The mental illness culture is alive and well: A reply to Page.

Counters S. Page's (see record 1987-05244-001) criticisms of the 1st and 3rd authors' (1983; see also PA, Vol 67:1855) study of the relationship between physical proximity of psychiatric facilities and patient admission rates, suggesting that statistics showing a steady increase in psychiatric admissions in the US and Canada indicate that a culture that tends to perceive problems as mental illness is real and growing. (14 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

New 11 beta-aryl-substituted steroids exhibit both progestational and antiprogestational activity

The syntheses of three 11 beta-aryl-19-norpregna-4,9-dien-3-one derivatives with 17-spirolactone and 17 beta-hydroxy-17 alpha-cyanoethyl substitutions are described. The progesterone agonist/antagonist activities of the new compounds are investigated using a recently developed tissue culture system that relies on the progesterone agonist up-regulation of the prostate-specific antigen (PSA) gene in female breast tumor cell lines. Two of the newly synthesized compounds exhibit mixed agonistic/antagonistic progestational activity.     

Pyridoxamine-amino acid chimeras in semisynthetic aminotransferase mimics

The transaminase activity of two new semisynthetic RNase-S proteins incorporating a pyridoxamine moiety at the active site has been evaluated. A chemically competent derivative of pyridoxamine phosphate was incorporated into the C-peptide fragments of these non-covalent protein complexes in the form of an unnatural coenzyme-amino acid chimera, 'Pam'. The chimeric Pam residue integrates the heterocyclic functionality of pyridoxamine phosphate into the side chain of an alpha- amino acid and was introduced instead of Phe8 into the C-peptide sequence via standard solid phase methodology. The two semisynthetic Pam-RNase constructs were designed to probe whether the native ribonuclease catalytic machinery could be enlisted to modulate a pyridoxamine-dependent transamination reaction. Both RNase complexes, H1SP and S1SP, exhibited modest rate enhancements in the Cu(II)- assisted transamination of pyruvate to alanine under single turnover conditions, relative to 5'-deoxypyridoxamine and the uncomplexed C- peptide fragments. Furthermore, multiple turnovers of substrates were achieved in the presence of added L-phenylalanine due to recycling of the pyridoxamine moiety. The modest chiral inductions observed in the catalytic production of alanine and the differences in reactivity between the two proteins could be rationalized by the participation of a general base (His12) in complex H1SP, and by the increased tolerance for large amino acid substrates by complex S1SP, which contains serine at this position. The pyridoxamine-amino acid chimera will be useful in the future for examining the coenzyme structure/ function relationships in a native-like peptidyl architecture.      

Transient kinetic studies on the interaction of Ras and the Ras-binding domain of c-Raf-1 reveal rapid equilibration of the complex

Transient kinetic methods have been used to analyze the interaction between the Ras-binding domain (RBD) of c-Raf-1 and a complex of H-Ras and a GTP analogue. The results obtained show that the binding is a two-step process, with an initial rapid equilibrium step being followed by an isomerization reaction occurring at several hundred per second. The reversal of this step determines the rate constant for dissociation, which is on the order of 10 s-1. The lifetime of the complex is therefore on the order of 50-100 ms, which is much shorter than the lifetime of GTP at the active site of H-Ras as determined by the intrinsic GTPase reaction. This suggests that multiple interactions of a single activated Ras molecule and Raf can occur, the number being limited by the competing interaction with GAP. The GDP complex of H-Ras binds more than 2 orders of magnitude more weakly than the GTP-analogue complex, mainly due to a significant weakening of the initial binding equilibrium reaction in the GDP state, thereby avoiding even short-lived recruitment of Raf to the plasma membrane by the inactive Ras form.     

Assessment of the clinical significance of anti-Dob

BACKGROUND: Anti-Dob is an uncommon antibody, and there are few data regarding its clinical importance. In the present case, the patient's transfusion management was based on both in vivo and in vitro assay results. CASE REPORT: A delayed hemolytic transfusion reaction was suspected in a 64-year-old white woman awaiting cardiac surgery when the transfusion of 1 unit of red cells failed to raise her hematocrit. Although direct antiglobulin tests were negative, antibody screening tests on samples drawn 9 days after transfusion were positive, and anti-Dob was identified, reacting to a titer of 4. 51Cr in vivo survival studies with incompatible Do(b+) red cells showed poor survival: 83.2 percent at 1 hour, 43 percent at 24 hours, and 29.6 percent at 48 hours and t1/2 = 19 hours (normal t1/2 = 25-35 days). A monocyte monolayer assay performed with the same incompatible Do(b+) donor red cells also indicated poor survival: 22 percent and 30 percent reactive monocytes, respectively, with and without the addition of complement (normal, 0-3%). The patient was given 4 Do(b-) red cell units without clinical signs or symptoms of a reaction. CONCLUSIONS: This example of anti-Dob was implicated in a delayed hemolytic transfusion reaction. The 51Cr survival studies and monocyte monolayer assay results indicated that the anti-Dob was clinically significant, requiring the use of Do(b-) red cells for transfusion.     

Inhibitors of glycogen phosphorylase b: synthesis, biochemical screening, and molecular modeling studies of novel analogues of hydantocidin

The synthesis and biochemical screening of four novel spironucleosides 1-4 against rabbit liver glycogen phosphorylase b (Gpb), along with molecular modeling studies on compound 2 and its 4-hydroxy analogue VII, have been presented. Gpb is a key enzyme of glycogen metabolism, and is known to be involved in the control of diabetes mellitus. The general strategy for synthesis involved base-catalyzed condensation of diethyl 2,4-dioxoimidazolidine-5-phosphonate (5) with either 2-deoxy-D-ribose or D-ribose, followed by sequential reactions involving ring-closure with phenylselenenyl chloride and reduction with tri-n-butyltin hydride catalyzed by azobisisobutyronitrile. Compounds 2 and 4 were found to be weak competitive inhibitors of Gpb, whereas 1 and 3 were inactive.