GENFILES: a computerized medical genetics information network. II. MEDGEN: the clinical genetics system

MEDGEN, a clinical genetics information storage and retrieval system, facilitates the handling of medical records for the central genetics clinic and satellite clinics conducted by the University of California, San Francisco. The system is part of the GENFILES genetics network, which handles all of the genetics data generated by a comprehensive medical genetics center. The clinical data stored on each patient include 1) diagnoses, which utilize McKusick catalog numbers as well as our own diagnostic codes; 2) relevant medical, gestational, and pregnancy history; 3) clinical manifestations (functional and structural); 4) karyotype information through a crosslink to the cytogenetics file; 5) ethnic origin of the patients; 6) physical status and sex of the patient; 7) laboratory studies, including results of metabolic tests; and 8) any additional remarks deemed necessary for complete understanding. The data, staff member attending, and physical location of each visit also are recorded.     

Modification and abolition of re-entry within the His-Purkinje system in man by diphenylhydantoin

The phenomenon of macrore-entry (Re) within the His-Purkinje system (HPS) was consistently observed in 10 of 19 patients during retrograde refractory period studies. Effects of intravenous infusion of diphenylhydantoin (DPH) on Re were studied in these 10 patients 10 minutes after completion of infusion (mean plasma level equal to 17.0 microgram/ml). Diphenylhydantoin modified determinants of Re in seven patients (group I) and abolished Re in the remaining three patients (group II). In group I, DPH shortened the critical V1 V2 from 310.0 +/- 30.5 to 292.9 +/- 25.6 msec (P less than 0.025) and critical V2 H2 intervals for Re from 201.4 +/- 18.4 to 185.0 +/- 13.8 msec (P greater than 0.05). In group II, DPH abolished Re in two of three patients by precluding attainment of critical V2 H2 intervals whereas Re was abolished in the remaining one patient despite attainment of critical V2 H2 intervals (vs control). For both groups, DPH significantly shortened functional and effective refractory periods of the HPS (P less than 0.001 and less than 0.01, respectively) without significantly affecting the effective refractory period of the ventricular muscle. Diphenylhydantoin either completely abolished or significantly shortened the retrograde gap zones in the HPS. It is concluded that diphenylhydantoin significantly shortens His-Purkinje system refractoriness, abolishing Re in the patients with higher degree of improvement in refractoriness.     

Effect of a specific platelet-activating factor antagonist on cardiovascular and peripheral cellular responses to colonic ischemia and reperfusion in anesthetized ponies

The role of platelet-activating factor in mediating the cardiovascular and peripheral cellular responses to large-colon ischemia and reperfusion, was explored in anesthetized ponies. A specific platelet-activating factor (PAF) antagonist (WEB 2086) was administered to a group of 6 ponies, and another 6 ponies (controls) were given an equivalent volume of saline solution, prior to 1 hour of large-colon torsion. After correction of the torsion, ponies were monitored during the reperfusion period. Significant (P < 0.05) hypotension and metabolic acidosis developed in all ponies after correction of colonic torsion, cardiac index increased initially, but then decreased significantly (P < 0.05) over the study period. Mean times between correction of torsion and onset of cardiac failure and death were not different between groups. Significant (P < 0.05) thrombocytopenia developed during the reperfusion period in control ponies, but not in WEB-treated ponies. Blood leukocyte concentration in control ponies was more variable and significantly (P < 0.05) decreased immediately upon reperfusion, compared with that in WEB-treated ponies. We conclude that although the cardiovascular responses to colonic ischemia and reperfusion are not prevented by use of a specific PAF-antagonist, specific peripheral cellular responses are mediated by PAF.     

A plea for consideration of ecological validity in the experimental psychology of mental retardation: a guest editorial

The point was raised that, despite considerable experimental effort, laboratory research concerning learning, memory, and cognition, more generally, has not produced a very remarkable increase in our understanding of retarded behavior. Our principal contention in this paper is that the experimental psychology of mental retardation, while basically seeking causal relations between theoretical constructs and retarded behavior, is suffering from some metatheoretical and methodological shortcomings. These include, basically, a prevalent failure to consider the ecological aspects of the phenomenon of mental retardation. Implications of ecological validity are important with respect to the basis upon which subjects are selected for experimentation, the rationale underlying manipulation of independent variables, the choice of dependent variables, and the definition of the boundaries that limit generalizations. Some suggestions were offered for the purpose of guiding experimental research toward more meaningful and socially relevant goals.     

Increased ubiquitin expression suppresses the cell cycle defect associated with the yeast ubiquitin conjugating enzyme, CDC34 (UBC3). Evidence for a noncovalent interaction between CDC34 and ubiquitin

The yeast ubiquitin (Ub) conjugating enzyme CDC34 plays a crucial role in the progression of the cell cycle from the G1 to S phase. In an effort to identify proteins that interact with CDC34 we undertook a genetic screen to isolate genes whose increased expression suppressed the cell cycle defect associated with the cdc34-2 temperature-sensitive allele. From this screen, the poly-Ub gene UBI4 was identified as a moderately strong suppressor. The fact that the overexpression of a gene encoding a single Ub protein could also suppress the cdc34-2 allele indicated that suppression was related to the increased abundance of Ub. Ub overexpression was found to suppress two other structurally unrelated cdc34 mutations, in addition to the cdc34-2 allele. In all three cases, suppression depended on the expression of Ub with an intact carboxyl terminus. Only the cdc34-2 allele, however, could be suppressed by Ub with an amino acid substitution at lysine 48 which is known to be involved in multi-Ub chain assembly. Genetic results showing allele specific suppression of cdc34 mutations by various Ub derivatives suggested a specific noncovalent interaction between Ub and CDC34. Consistent with this prediction, we have shown by chemical cross-linking the existence of a specific noncovalent Ub binding site on CDC34. Together, these genetic and biochemical experiments indicate that Ub suppression of these cdc34 mutations results from the combined contributions of Ub-CDC34 thiol ester formation and a noncovalent interaction between Ub and CDC34 and therefore suggest that the correct positioning of Ub on a surface of the ubiquitin conjugating enzyme is a requirement of enzyme function.