Antibody catalysis of peptidyl-prolyl cis-trans isomerization in the folding of RNase T1

An antibody generated to an alpha-keto amide containing hapten 1 catalyzes the cis-trans isomerization of peptidyl-prolyl amide bonds in peptides and in the protein RNase T1. The antibody-catalyzed peptide isomerization reaction showed saturation kinetics for the cis-substrate, Suc-Ala-Ala-Pro-Phe-pNA, with a kcat/Km value of 883 s-1.M-1; the reaction was inhibited by the hapten analog 13 (Ki = 3. 0 +/- 0.4 microM). Refolding of denatured RNase T1 to its native conformation also was catalyzed by the antibody, with the antibody-catalyzed folding reaction inhibitable both by the hapten 1 and hapten analog 13. These results demonstrate that antibodies can catalyze conformational changes in protein structure, a transformation involved in many cellular processes.     

Anatomic correction of transposition of the great vessels

We present a new approach for anatomic correction of transposition of the great arteries. The two coronary arteries, with a piece of the aortic wall attached, are transposed to the posterior artery. The two aortic openings are closed with a patch. The aorta and pulmonary artery are transected, contraposed, ant then anastomosed. The interventricular septal defect is closed with a patch, through a right ventriculotomy approach, because the right ventricle is no longer part of the systemic circulation. Two patients, aged 3 months and 40 days weighing 4,200 and 3,700 grams, respectively, were operated upon with deep hypothermia and total circulatory arrest. There was good recovery from the operation, with normal cardiocirculatory conditions. Renal failure developed in the first patient, and she died on the third postoperative day. During this time the cardiocirculatory conditions were good. The second patient made an uneventful recovery. Hemodynamic studies 20 days after the operation showed complete correction of the malformation. Five and one-half months after the operation, he weighs 7,500 grams, and his development is very good. We believe that this operation will be reproducible by most cardiovascular septal defect and pulmonary hypertension.     

The CTFA Evaluation of Alternatives Program: an evaluation of in vitro alternatives to the Draize primary eye irritation test. (Phase III) surfactant-based formulations

The CTFA Evaluation of Alternatives Program is an evaluation of the relationship between data from the Draize primary eye irritation test and comparable data from a selection of promising in vitro eye irritation tests. In Phase III, data from the Draize test and 41 in vitro endpoints on 25 representative surfactant-based personal care formulations were compared. As in Phase I and Phase II, regression modelling of the relationship between maximum average Draize score (MAS) and in vitro endpoint was the primary approach adopted for evaluating in vitro assay performance. The degree of confidence in prediction of MAS for a given in vitro endpoint is quantified in terms of the relative widths of prediction intervals constructed about the fitted regression curve. Prediction intervals reflect not only the error attributed to the model but also the material-specific components of variation in both the Draize and the in vitro assays. Among the in vitro assays selected for regression modeling in Phase III, the relationship between MAS and in vitro score was relatively well defined. The prediction bounds on MAS were most narrow for materials at the lower or upper end of the effective irritation range (MAS = 0-45), where variability in MAS was smallest. This, the confidence with which the MAS of surfactant-based formulations is predicted is greatest when MAS approaches zero or when MAS approaches 45 (no comment is made on prediction of MAS > 45 since extrapolation beyond the range of observed data is not possible). No single in vitro endpoint was found to exhibit relative superiority with regard to prediction of MAS. Variability associated with Draize test outcome (e.g. in MAS values) must be considered in any future comparisons of in vivo and in vitro test results if the purpose is to predict in vivo response using in vitro data.     

Molecular cloning of mouse glycolate oxidase. High evolutionary conservation and presence of an iron-responsive element-like sequence in the mRNA

Iron regulatory proteins (IRPs) control the synthesis of several proteins in iron metabolism by binding to iron-responsive elements (IREs), a hairpin structure in the untranslated region (UTR) of corresponding mRNAs. Binding of IRPs to IREs in the 5' UTR inhibits translation of ferritin heavy and light chain, erythroid aminolevulinic acid synthase, mitochondrial aconitase, and Drosophila succinate dehydrogenase b, whereas IRP binding to IREs in the 3' UTR of transferrin receptor mRNA prolongs mRNA half-life. To identify new targets of IRPs, we devised a method to enrich IRE-containing mRNAs by using recombinant IRP-1 as an affinity matrix. A cDNA library established from enriched mRNA was screened by an RNA-protein band shift assay. This revealed a novel IRE-like sequence in the 3' UTR of a liver-specific mouse mRNA. The newly identified cDNA codes for a protein with high homology to plant glycolate oxidase (GOX). Recombinant protein expressed in bacteria displayed enzymatic GOX activity. Therefore, this cDNA represents the first vertebrate GOX homologue. The IRE-like sequence in mouse GOX exhibited strong binding to IRPs at room temperature. However, it differs from functional IREs by a mismatch in the middle of its upper stem and did not confer iron-dependent regulation in cells.     

The venotonic drug hydroxyethylrutosiden does not prevent or reduce docetaxel-induced fluid retention: results of a comparative study

PURPOSE: Fluid retention, which includes peripheral edema, ascites, pleural or pericardial effusion, or a combination of these that is sometimes associated with significant weight gain, is one of the most troublesome cumulative side effects of docetaxel. A suggestive observation from the data base available at the manufacturer (Rhone-Poulenc Rorer) was that patients who received venotonic drugs appeared to tolerate more courses of docetaxel. This prompted a comparative study to investigate whether the venotonic drug hydroxyethylrutosiden could reduce or delay docetaxel-related fluid retention. METHODS: A total of 85 patients with metastatic breast cancer who were treated with docetaxel at a dose of 100 mg/m2 with corticoid comedication were allocated to receive either 300 mg hydroxyethylrutosiden given orally four times daily (group A) or no hydroxyethylrutosiden (group B). The end point for analysis was the development of fluid retention of > or = grade 2. RESULTS: Fluid retention of > or = grade 2 was reported in 14 of 42 patients (33%) in group A and in 15 of 43 patients (35%) in group B and occurred after a median of 4 cycles of docetaxel in both groups. Weight gain was similar in groups A and B. CONCLUSION: We conclude that hydroxyethylrutosiden does not reduce or delay the incidence and severity of docetaxel-related fluid retention.     

Interaction of kunjin virus with octyl-D-glucoside extracted Vero cell plasma membrane

Initial experiments using whole cells have shown that there were specific and saturable interactions between kunjin (KUN) virus and receptor molecules on the Vero cell surfaces. Solubilisation of Vero cell plasma membranes with octyl-D-glucoside (OG) yielded an extract which also interacted specifically with KUN virus. This was proven using electron microscopy. When the virus-OG-extract complex was exposed onto Vero cell monolayers, no KUN virus was observed to enter into the whole cells. This would imply that there was virus-receptor interaction with the OG-extract leaving no free virus to attach to the whole cells. The attachment kinetics of KUN virus was studied further using the Scatchard analysis which indicated the involvement of more than one interactive macromolecule in the attachment event.     

APIC position paper: hepatitis C exposure in the health care setting. Association for Professionals in Infection Control and Epidemiology, Inc

The Association for Professionals in Infection Control and Epidemiology, Inc (APIC), is a multidisciplinary, voluntary, international organization of professionals who practice infection control and the application of epidemiology in all health settings. APIC is an international leader in prevention and control of infection transmission.     

Dental microwear of Griphopithecus alpani

The examination of microscopic dental wear allows inferences to be made about diet in extinct species. This study reconstructs the diet of Griphopithecus alpani, a 15 Ma fossil hominoid from the Miocene site of Pa?alar in north-western Turkey, using scanning electron microscopy (SEM) to examine the microscopic wear on its molar teeth. The microwear patterns of Griphopithecus are compared with those of three extant hominoid taxa-Gorilla gorilla gorilla, Pan troglodytes verus, and Pongo pygmaeus pygmaeus. The microwear on three occlusal wear surfaces is examined in this study, and sex and age differences are also included. Analysis of variance is performed on the following microwear variables-feature density, pit density, striation density, the ratio of pits relative to striations, pit widths, and striation widths. Griphopithecus has significantly higher microwear feature densities and higher percentages of pits than Gorilla. It also has larger pit frequencies and narrower striations than both Pan and Gorilla. There are no significant differences between the microwear patterns of Griphopithecus and Pongo. This suggests that the diet of Gripho-pithecus was more similar to that of Pongo, which consumes mainly fruit, and occasionally hard and unripe fruits and nuts, than to that of Pan and Gorilla. In addition, the high percentage of pits displayed by Griphopithecus may indicate that it was ingesting harder fruits and/or objects than the extant hominoids, although this is not a significant difference. There also are consistent variations in the microwear present on the three different wear facets examined in the study-Phase II facets display more microwear and pitting than the Phase I surface examined. The results of this study do not indicate variation in dental microwear according to sex or age.