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Biomedical subjects

P Schroeder

Publications and source records attributed to P Schroeder.

At least 37 records · Page 2Linked to original sources
PubMed1996

Identification and characterization of a C(K/R)TC motif as a common epitope present in all subtypes of hepatitis B surface antigen.

The a determinant of hepatitis B surface antigen (HBsAg) is the most critical determinant for both diagnosis and immunoprophylaxis of the hepatitis B virus. We have used synthetic peptides and an anti-a mAb to identify a peptide sequence corresponding to amino acid residues 117 to 128 of HBsAg as an antigenic epitope contributing to the a determinant. Compared to the native protein HBsAg, the cyclic form of the peptide (aa 117-128) is only 20-fold less effective, whereas the linear form of the peptide is 160-fold less effective in the inhibition of mAb binding to HBsAg. Based on these results, we have postulated a previously unidentified disulfide bond between residue Cysl21 and Cysl24. Individual substitution of amino acids in the peptide (aa 117-128) with alanine identified three residues Cys121, Thr123, and Cys124 as the most critical residues for mAb recognition. Substitution of alanine for any one of the three residues caused a substantial loss in binding free energy (greater than 4.5 kcal/mol). Sequence analysis indicated that the C(K/R)TC motif is highly conserved among 100 subtypes and mutants of HBsAg isolates. Collectively, these results show that the cyclic C(K/R)TC motif is an essential part of the a determinant of HBsAg. Synthetic peptides containing the C(K/R)TC motif are potentially useful as alternative hepatitis B vaccines and as diagnostic reagents for the detection of the hepatitis B virus.

Amino Acid Sequence↗
PubMed1996

Quality field.

Explore the source record for details and available documents.

Health Services Research↗
PubMed1995

Isolation and characterization of a Clostridium botulinum C2 toxin-resistant cell line: evidence for possible involvement of the cellular C2II receptor in growth regulation.

Clostridium botulinum C2 toxin, which consists of the binding component C2II and the enzyme component C2I, acts on eukaryotic cells by selective ADP-ribosylation of G-actin. To obtain C2 toxin-resistant cells, we mutagenized CHO-K1 cells with N-nitroso-N-methylurea and selected for C2 resistance. Cells which survived the selection procedure with 50 ng of C2I and 100 ng of C2II per ml were obtained with a frequency of 30 x 10(-6). The colony-forming ability of CHO wild-type cells was reduced to 50% with 10 ng of C2I and 20 ng of C2II per ml. In contrast, the colony-forming ability of the isolated CHO mutant cells was not influenced by up to 200 ng of C2I and 400 ng of C2II per ml. Toxin-induced ADP-ribosylation of G-actin was not impaired in lysates of mutant cells. The C2 toxin-resistant phenotype remained sensitive to the cell-rounding activities of cytotoxins from C. perfringens (iota-toxin), C. novyi, C. difficile, and C. botulinum (C3) and to cytochalasin D. Binding of component C2II was impaired in resistant CHO cells, suggesting mutation of the toxin cell surface receptor. Serum factors protected wild-type cells against the cytotoxic effect of C2 toxin. Furthermore, the C2-resistant phenotype correlated with an increased serum dependency. The data suggest that the action of C. botulinum C2 toxin is mediated by its binding and uptake via a cell surface receptor which might be involved in growth regulation.

ADP Ribose Transferases↗
PubMed1994

Tamoxifen induces hepatic aneuploidy and mitotic spindle disruption after a single in vivo administration to female Sprague-Dawley rats.

Tamoxifen has found extensive use in the treatment of all stages of human breast cancer. The efficacy of tamoxifen treatment for the prevention of second primary tumors and its chemosuppressive action in animal models have led to initiation of clinical trials to test its efficacy for prevention of this disease in women. Recently, tamoxifen has been shown to induce hepatocellular carcinomas in rats. For determination of the mechanism of induction of these tumors and assessment of the possibility of risk of human cancer development from tamoxifen treatment, female Sprague-Dawley rats (five rats per treatment) were administered tamoxifen at doses ranging from 0.3 to 35 mg/kg. One day after treatment, the rats were sacrificed, and the hepatocytes were isolated and cultured for 50 h. Colcemid was added 3 h prior to harvest, and the hepatocytes were then prepared for karyotypic evaluation. One hundred metaphase spreads were examined per animal. Tamoxifen treatment resulted in the induction of aneuploidy in approximately 70% of the examined hepatocytes at the doses used. In addition, premature condensation (2-10%) and endoreduplication (5-10%) were observed in hepatocytes of rats treated with tamoxifen. Furthermore, exchanges between chromosomes as well as chromosome breakage were observed. Examination of the cultured hepatocytes from rats treated with tamoxifen by electron microscopy demonstrated both unipolar spindles and incompletely elongated spindles. Exposure of rats to a single in vivo dose of tamoxifen produced multiple changes in rat hepatocytes including clastogenic damage at doses comparable to that administered to humans. The occurrence of aneuploidy induction, premature condensation, chromosome breakage, and improper mitotic spindle formation indicates that risk versus benefit of tamoxifen treatment should be carefully evaluated.

Aneuploidy↗
PubMed1994

The development and evaluation of new versions of the written examination for the American Heart Association Advanced Cardiac Life Support provider course.

STUDY OBJECTIVE: To create new versions of the written, multiple-choice examination used in the American Heart Association (AHA) Advanced Cardiac Life Support course, evaluate their reliability and difficulty, and then design revised versions with improved reliability and of standardized difficulty. DESIGN: Psychometric evaluation of new versions of the AHA Advanced Cardiac Life Support test and revisions. SETTING: AHA Advanced Cardiac Life Support courses. PARTICIPANTS: Candidates for completion of AHA Advanced Cardiac Life Support provider courses in five states. INTERVENTION: The course content was divided into 11 content areas that were weighted for importance and appropriateness for testing in a multiple-choice format. The weights were used to construct a blueprint for a 50-question, multiple-choice examination. Five versions of the examination were then constructed based on the content blueprint, drawing from new questions and expert revision of previously written questions. Reliability and difficulty were assessed using 915 administrations at five different sites nationwide. The initial test versions differed in their degree of difficulty, which was not explained by demographic factors. The results were used to revise three of the versions to improve reliability and equalize difficulty of the versions. MEASUREMENTS AND MAIN RESULTS: The final five versions have estimated reliability ranging from Cronbach's alpha of .62 to .86. Mean scores ranged from 87.4% to 89.1%. CONCLUSION: After field testing and revision, five examinations with acceptable reliability and roughly equal difficulty were constructed. The new examinations test the participants' knowledge of important aspects of resuscitation science and practice based on a blueprint of the course content.

American Heart Association↗
PubMed1994

Linking key functions and important aspects of care: perspectives on perioperative, medical-surgical, and perinatal nursing.

Most professions are defined, at least in part, by the functions they perform. Nursing, it its pursuit of a definition, has begun to define its scientific functional base. This article attempts to advance that definition by outlining generic functions that define the practice of nursing. The study described in the article used these generic functions to determine what quality professionals perceived to be the key functions in medical-surgical, perioperative, and perinatal nursing. Once defined, these key functions can serve as the basis for specialty discipline standards development, research, indicator development, and competency definition, assessment, and improvement.

Attitude of Health Personnel↗
PubMed1994

Adenine nucleotides regulate ADP-ribosylation of membrane-bound actin and actin-binding to membranes.

Adenine nucleotides were shown to increase the ADP-ribosylation of actin by Clostridium perfringens iota and Clostridium botulinum C2 toxin in membranes from human platelets, hamster fat cells, rat liver- and rat brain cells. ATP and ATP gamma S were the most effective agents with ATP showing half-maximal and maximal effects at about 2 and 10 microM, respectively. The rank order of various adenine nucleotides were ATP = ATP gamma S > ADP > AMP-PNP >> AMP = cAMP. Guanine nucleotides showed the same rank order of potencies but were less effective than adenine nucleotides. Adenine nucleotides which increased ADP-ribosylation were able to release actin from membranes. [32P]ADP-ribosylated rabbit skeletal muscle actin, which is unable to polymerize, was used as tool to study membrane-binding of actin. The [32P]ADP-ribosylated actin bound to stripped rat liver membranes in a saturable, time- and temperature-dependent manner. ATP inhibited the binding of ADP-ribosylated actin with a half-maximal and maximal inhibitory concentration at about 50 and 300 microM, respectively. The data indicate that actin-binding to membranes is prevented or reversed in the presence of adenine nucleotides thereby increasing the accessibility of actin for ADP-ribosylation by toxins.

ADP Ribose Transferases↗