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Biomedical subjects

F Hutchinson

Publications and source records attributed to F Hutchinson.

At least 19 recordsLinked to original sources
PubMed1998

A mutation spectra database for bacterial and mammalian genes: 1998.

This database consists of over 24 000 mutations in 18 viral, bacterial, yeast or mammalian genes. The data are grouped as sets of DNA base sequence changes or spectra caused by a particular mutagen under defined conditions. The spectra are available on the World Wide Web at http://info.med.yale.edu/mutbase/ in two formats; in text format that can be browsed on-line or downloaded for use with a text editor and in dBASEIII format for use, after downloading, by relational database programs or by spreadsheets. Researchers are encouraged to submit DNA sequence changes to a suitable mutation database such as ours. A data entry program, MUTSIN, can be retrieved from this site. MUTSIN diagrams each mutation on the computer screen and alerts the user to any discrepancies.

Animals↗
PubMed1997

A mutation spectra database for bacterial and mammalian genes.

Each mutation spectrum in this database is a dataset of changes in DNA base sequence in mutations induced in a gene by a particular mutagen (including spontaneous processes) under defined conditions. There are 240 datasets with 24 500 mutants in nine bacterial genes, two phage genes, five mammalian genes and one yeast gene. The database is available on the Web at http://info.med.yale.edu/mutbase/ . The data tables can be viewed on the Web and downloaded in text form for local use. The data are also available in dBASE III, a format which can be utilized by essentially any desktop computer database program or spreadsheet, and makes feasible analyses of a large number of mutants. Researchers are invited to submit additional data. A data entry program, MUTSIN, diagrams each mutation on the computer screen as the data are entered and alerts the user to any discrepancies between the entry and the gene sequence.

Bacteriophage P22↗
PubMed1997

Calculation by microdosimetric methods of the formation by a single high-energy photon or electron of two lesions in the same DNA molecule.

The formation by a single high-energy photon or electron of two lesions (such as double-strand breaks) in the same DNA molecule is calculated by microdosimetric methods. The result is similar to a previous calculation using a target theory approach. Thus, it is reasonably certain that, for > or = 1 Gy of sparsely ionizing radiation acting on a DNA molecule of > or = 10(6) base pairs, < or = 3% of two-hit events such as deletions are from a single radiation event.

DNA↗
PubMed1996

A general database for DNA sequence changes induced by mutagenesis of several bacterial and mammalian genes.

This electronic database is a collection of 225 sets of data on mutations in more than twenty-three thousand mutants (October, 1995) in eleven bacterial genes, five mammalian genes and one gene in yeast cells. Each dataset consists of the changes in DNA sequence in the mutants, typically tens to hundreds, induced by mutagenesis of a particular cell line under specific conditions. The database is available on the Internet and on diskettes, and is periodically updated. Researchers are invited to submit additional data. A data entry program, MUTSIN, is available that diagrams each mutation on the computer screen as entered and alerts the user to any inconsistency between the entry and the wild type gene sequence.

Animals↗
PubMed1996

Unexplained hepatitis C virus antibody seroconversion in established blood donors.

BACKGROUND: Understanding of the epidemiology and natural history of hepatitis C virus (HCV) infection is incomplete without reference to the early phase of infection. The prevalence of HCV infection is well documented in numerous reports. The seroconversion pattern in previously antibody-negative blood donors provides a model for the study of the incidence and transmission of HCV infection. STUDY DESIGN AND METHODS: Records of HCV antibody tests at the West Midlands Blood Transfusion Centre were reviewed to determine the seroconversion rate in 1994 among previously anti-HCV-negative blood donors. Seroconverting donors were counseled to investigate the possible routes of infection. RESULTS: In 1994, blood donations (n = 256,935) were collected from 149,370 donors; 24 donors (0.016%; 1/6224) were positive in the screening enzyme-linked immunosorbent assay (ELISA) and the third-generation recombinant immunoblot assay (RIBA-3). Two donors previously negative for HCV antibody in ELISA were positive in both tests in 1994. Four donors positive in ELISA and indeterminate in RIBA-3 in 1993 reacted positively in both tests in 1994. One donor negative for HCV antibody on previous screening reacted positively in ELISA and was indeterminate in RIBA-3 in 1994 and has become positive in both tests in 1995. A further 43 donors negative for HCV antibody on previous screening reacted positively in ELISA and were indeterminate in RIBA-3 in 1994. CONCLUSION: Documented seroconversion can take place in the absence of exposure to recognizable risk factors for the infection. The index donation or the donation immediately preceding seroconversion may be positive for HCV RNA in the polymerase chain reaction.

Blood Donors↗
PubMed1996

Formation of two double-strand breaks in the same DNA molecule by a single high-energy photon or ionizing particle.

I calculate the probability that a single high-energy ionizing particle or photon makes two widely spaced double-strand breaks in the same DNA molecule. Deletions (or inversions) between two breaks formed by the same incident particle are linear in radiation dose and occur even at extremely low dose-rates; deletions between breaks induced by separate particles are quadratic in dose and are much fewer at very low dose-rate. The calculations show that for a few grays of sparsely ionizing radiations such as fast electrons, X-rays of gamma-rays, the formation of two double-strand breaks in a DNA molecule 1 megabase in size should be nearly entirely quadratic in dose. For heavily ionizing particles such as alpha particles from radon products, the linear and quadratic terms are comparable in size. These conclusions are robust and insensitive to details of the calculations. The results are essentially the same for DNA in a random coil configuration and for DNA uniformly and randomly distributed within a sphere.

Chromosome Inversion↗
PubMed1995

Analysis of deletions induced in the genome of mammalian cells by ionizing radiation.

A theory is presented for the distribution in size of deletions induced by ionizing radiation, based on three assumptions: (1) deletions that are observed delete part or all of a gene to make a mutation, but not adjacent DNA sequences essential for survival of the mutant; (2) deletions are distributed at random along the DNA; (3) the probability of formation is proportional to the rate at which the two endpoints, which must meet to form the deletion, collide with each other. Experimental data for radiation-induced deletions in human and hamster hprt genes are in good agreement with calculations that assume the inducing lesion does not break the intracellular chromatin fiber; calculations assuming the inducing lesion is a break are not a good fit to the data. The low frequency of deletions observed in the hamster aprt gene is shown to be a consequence of the small gene size and the presence of a nearby essential DNA sequence, ensuring that most deletions affecting the gene also delete the essential sequence and are thus not observed.

Adenine Phosphoribosyltransferase↗
PubMed1995

Hepatitis C virus seroconversion rate in established blood donors.

The results of hepatitis C virus (HCV) antibody test of 237,813 blood donations collected from 143,815 donors by the West Midlands Blood Transfusion Centre in 1993 were analyzed retrospectively in order to determine the seroconversion rate among established previously anti-HCV negative donors. Three hundred sixteen (0.22%; 1 in 455) donors were positive by the enzyme linked immunosorbent assay (ELISA) screening test and 34 (0.024%; 1 in 4,230) donors were positive by ELISA and the Recombinant Immuno Blot Assay (RIBA). Three donors previously negative for HCV antibody reacted positively by both tests. The annual seroconversion rate was calculated as one in 35,937 donors. This figure argues against limitation of HCV antibody screening to new blood donors. A further 45 donors negative on previous screening reacted positively by ELISA and were indeterminate by RIBA. Unexpectedly, lapsed blood donors first tested for HCV antibody in 1993 had high positive reaction rates by ELISA and RIBA, which was significantly (P < 0.001) higher than those of new donors. RIBA-positive reaction rate among ELISA-positive donors was significantly higher amongst males than females (P < 0.001).

Adult↗
PubMed1995

Malunions of the distal radius: treatment options.

Approaches to malunion of the distal radius may be viewed as a hierarchy of surgical options with increasing complexity and potential surgical morbidity. Choice of an appropriate surgical approach requires consideration of the patient's activity level, as well as the anatomic distortion that is present. In the posttraumatic situation, there is lack of agreement as to management of the distal ulna. Relative increased ulnar length and triangular fibrocartilage insufficiency make use of partial resection techniques more difficult. Osteotomy of the distal radius with or without a concomitant distal ulna procedure most nearly re-creates the preinjury situation anatomically and is seeing increasingly widespread application. It continues to be a challenging procedure from a technical standpoint. The need for procedures discussed in this review could be drastically reduced by a more aggressive approach to the initial fracture.

Arthrodesis↗
PubMed1995

Decision making in distal radius fractures.

In distal radius fractures, function follows restoration of preinjury anatomic landmarks. The allowable deviation from these measurements is relatively small if optimal results are to be achieved, particularly in younger individuals. A hierarchy of treatment options--characterized by increasing invasiveness--exists for treating these injuries. As this hierarchy is ascended, treatment-related complications increase. It appears reasonable to select the least invasive treatment option capable of achieving satisfactory anatomic alignment. Hand and extremity function must be addressed early, and a conscientious effort must be exerted to avoid residual stiffness or the development of reflex sympathetic dystrophy.

Colles' Fracture↗
PubMed1994

Induction of tandem-base change mutations.

Four databases with sequence changes for 12000 mutations in mammalian and bacterial cells were searched for genotoxic agents inducing tandem mutations, in which two adjacent base pairs are changed. Ultraviolet light induces about one CC > TT per 10-20 mutations, and other tandem-base changes at about half that frequency. There is strong evidence that cis-diammine dichloroplatinum (II) induces tandems. These results suggest that tandem-base changes are induced by agents that damage two adjacent base pairs in DNA. Tandems, particularly CC > TT, can be used as indicators of exposure to ultraviolet light, as in genes in skin cells exposed to sunlight. Oxidizing agents such as superoxide and ionizing radiation do not induce a significant level of tandem-base changes (such as CC > TT) in double-strand DNA, so such mutations are not a useful indicator of exposure to mutagens of this type. All conclusions are equally valid for bacterial and mammalian cells.

Animals↗
PubMed1994

Treatment of os calcis fractures by open reduction and internal fixation.

Over a 3-year period, 47 displaced intra-articular fractures of the os calcis in 43 patients underwent open reduction and internal fixation. A significant feature of this series is that computed tomography was used to assess all fractures both before and after surgery. Seventy-seven percent demonstrated a consistent fracture pattern with four major bone fragments. Patients underwent clinical assessment 1 year after injury; thirty-six feet (76.6%) were rated satisfactory and 11 (23.4%) were rated unsatisfactory. An unsatisfactory clinical outcome was significantly correlated with failure to obtain or maintain a satisfactory reduction (P = .004) and also with workers' compensation or liability status (P = .013). The degree of initial comminution, bilateralism, calcaneocuboid joint involvement, patient age, joint depression versus tongue-type fracture pattern, and Bohler's angle at follow-up did not correlate with the final clinical result. Postoperative computed tomography in the coronal plane was found to be mandatory for assessment of joint congruity and restoration of an adequate fibulocalcaneal space.

Adolescent↗
PubMed1994

Yale database for DNA sequence changes in mutagenesis.

The Yale database contains sequence changes in mutations induced in a number of bacterial, mammalian and yeast genes. It contains data in electronic form on more than 17,000 mutations (July, 1994), is periodically updated, and is available without cost on Internet and on diskettes. Researchers are invited to contribute additional results; a data entry program, MUSTIN, is provided to facilitate adding new data and to minimize errors.

Animals↗
PubMed1993

Induction of large DNA deletions by persistent nicks: a new hypothesis.

DNA deletions of more than one or two base pairs are induced frequently enough so that these form a reasonable fraction of mutations for only a few mutagens. Of these agents, some such as ionizing radiations form DNA double-strand breaks, and very large deletions are thought to result from a DNA end from one break ligating with a second break on the same DNA molecule. However, deletions of kilobase pairs and more are sometimes induced by ionizing radiation at a higher rate than can be accounted for by the numbers of double-strand breaks. Published data on induced deletions in particular Escherichia coli strains suggest a process involving a single lesion that could explain several features of large deletions: frequent occurrence in mammalian cells and scarcity in prokaryotes, nonrandom location which is perhaps associated with locations of origins of replication, and differences in the fraction of deletions among mutations in various genes. Some agents inducing deletions make single-strand nicks, not double-strand breaks, and the proposed mechanism hypothesizes that the inducing lesion is a persistent nick in one DNA strand--for example, a radiation-induced single-strand break with associated damage on the complementary strand that interferes with repair.

Animals↗
PubMed1993

Molecular biology of mutagenesis of mammalian cells by ionizing radiation.

In mammalian cells, ionizing radiation induces comparable numbers of point mutations (principally base changes, frameshifts and small deletions) and of large deletions of more than a hundred base pairs. The latter are formed either by misrepair of an end from one double-strand break with an end from another, or by a second mechanism which, it is suggested, is initiated by slowly repaired single-strand nicks. The ratio of deletions to point mutations is variable from one gene to another, and is greatest for genes in which very large deletions still allow cells to survive.

Animals↗
PubMed1992

Published data on mutagenesis by ionizing radiation of plasmids in solution probably reflect in part the specificity of adventitious transition metal ions complexed to the DNA.

A number of recent papers show that single base changes induced by mutagenesis with ionizing radiation of genes on plasmids in solution, followed by transfection into mammalian or bacterial cells for assay, are mostly at G:C base pairs, with mutagenic hot spots. Genes irradiated in mammalian or bacterial cells, on the other hand, have comparable numbers of base changes at all sites, with no evidence for hot spots. The differences are ascribed to induction of many base change mutations in vitro by reactions catalyzed by adventitious transition metal ions complexed to the DNA. Reasons are given why this process should play a much smaller role in vivo.

Base Composition↗