Fate of biomedical research protocols and publication bias in France: retrospective cohort study

Objectives To describe the fate of protocols approved by the French research ethics committees, a national system created by the French 1988 Huriet-Sérusclat Act; to assess publication bias at a national level.Design Retrospective cohort study.Setting Representative sample of 25/48 French research ethics committees in 1994.Protocols 649 research protocols approved by committees, with follow-up information.Main outcome measures Protocols'' initial characteristics (design, study size, investigator) abstracted from committees'' archives; follow-up information (rates of initiation, completion, and publication) obtained from mailed questionnaire to principal investigators.Results Completed questionnaires were available for 649/976 (69%) protocols. Of these, 581 (90%) studies were initiated, 501/581 (86%) were completed, and 190/501 (38%) were published. Studies with confirmatory results were more likely to be published as scientific papers than were studies with inconclusive results (adjusted odds ratio 4.59, 95% confidence interval 2.21 to 9.54). Moreover, studies with confirmatory results were published more quickly than studies with inconclusive results (hazard ratio 2.48, 1.36 to 4.55).Conclusion At a national level, too many research studies are not completed, and among those completed too many are not published. We suggest capitalising on research ethics committees to register and follow all authorised research on human participants on a systematic and prospective basis.     

Neutral microprotein, a novel human plasma and urinary protein associated with a yellow-brown chromophore. Isolation from protein HC preparations and partial characterization

An apparently novel human plasma and urinary protein of low molecular weight was isolated from several highly purified preparations of protein HC by gel chromatography and high voltage electrophoresis with a yield of about 8 mg/g. The protein has a molecular weight of about 20,000, neutral electrophoretic mobility at pH 6.5 and a high content of half-cystine. It is associated with a yellow-brown chromophore like protein HC and could be demonstrated in all investigated preparations of isolated human, rabbit and guinea-pig protein HC and alpha 1-microglobulin.     

Changes in the size of the myocardial damaged area in postischemic reperfusion

The changes in the size of the myocardial injury area during reperfusion after the coronary occlusion-induced ischemia lasting 30 minutes are phasic in nature. Until 3.5 h the injured area increases and after 23.5 h relatively diminishes. After a more prolonged ischemia such manifestations are either unmarked or absent. Ischemia lasting from 30 min to 4 hours followed by reperfusion, as compared with ischemia of the same duration without reperfusion, normally gives rise to the formation of an area of injury, which is less or occasionally equal in size. The data obtained and reported indicate that in the area of coronary occlusion there are groups of cardiomyocytes that differ as regards the resistance to ischemia.     

N alpha-arylsulfonyl-omega-amidinophenyl-alpha-aminoalkyl-carboxylic acid amides as specific thrombin inhibitors

Structure-activity relationships for the inhibition of thrombin and trypsin by N alpha-substituted amidinophenyl-alpha-aminoalkylcarboxylic acid amides are presented. Secondary cyclic amides of N alpha-substituted 4-amidinophenylalanine and 2-amino-5-(4-amidinophenyl)valeric acid were found to be potent and specific inhibitors of thrombin, whereas trypsin was inhibited strongly by primary amides of 2-amino-4-(4-amidinophenyl) butyric acid. For this type of inhibitor the carbon amide structure seems to play a decisive role in the enzyme-inhibitor interaction.     

An improved purification method for cytosolic malate dehydrogenase from several sources

A new purification method for cytosolic malate dehydrogenases from several sources has been developed. The procedure, employing chromatographies on 5'AMP-Sepharose, DEAE-Sephacel and Blue-Sepharose, allows for a rapid isolation of the enzyme (approximately 40 hours), in large quantities, with good yields (45-54%). The specific activity of final preparations were around 1300 I.U./mg and were judged homogeneous by polyacrylamide gradient gel and sodium dodecyl sulfate polyacrylamide gel electrophoresis, high performance size exclusion chromatography and isoelectric focusing.     

Elementary steps in protein folding.

The mechanism of protein folding is under intense theoretical and experimental investigation. From stopped-flow mixing experiments we have detailed knowledge of processes slower than about 1 ms, but until recently little was known about folding and unfolding reactions on the microsecond to nanosecond time scale. The use of novel techniques allowed to explore the elementary steps in protein folding, such as intrachain diffusion and formation of alpha-helices, beta-hairpins and loop structures. This brief review discusses the time scales of these early elementary events which are crucial for the understanding of how proteins fold.     

Characterization of a substance P-Gly12 amidating enzyme in human cerebrospinal fluid

Enzyme activity capable of converting the glycine-extended substance P precursor, substance P-Gly12, into substance P was purified from human cerebrospinal fluid. The conversion reaction was monitored by radioimmunoassay measurement of substance P formation. The chemical identity of the product was verified by reversed-phase HPLC. The enzyme reaction was stimulated by Cu(II) ion and ascorbic acid and inhibited by the presence of diethyldithiocarbamate. By HPLC molecular sieving, the major enzyme activity appeared as a protein of 26,000 molecular weight.     

Comparative incidence of reticuloendothelial tumors in C57BL mice after exposure to tritiated water

A total of 2,377 C 57 Bl/6M mice were assigned to control groups and experimental groups exposed to tritiated water administered as a pulse injection or in drinking water, at a dose of 1.0 microCi per injection or per ml of drinking water. Weanlings were observed for the duration of life span. Data analysis was based on two coefficient estimates (1) individual carcinogenic induction coefficient and (2) specific tumorigenic induction coefficient. The carcinogenic potency of tritium was found to be dual in nature in enhancing the absolute induction of lymphocytic lymphomas in both sexes as well as their relative induction in competition with reticulo-endothelial tumors of other types.