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Biomedical subjects

W Clark

Publications and source records attributed to W Clark.

At least 91 records · Page 5Linked to original sources
PubMed1987

Base sequence effects in double helical DNA. I. Potential energy estimates of local base morphology.

A series of potential energy calculations have been carried out to estimate base sequence dependent structural differences in B-DNA. Attention has been focused on the simplest dimeric fragments that can be used to build long chains, computing the energy as a function of the orientation and displacement of the 16 possible base pair combinations within the double helix. Calculations have been performed, for simplicity, on free base pairs rather than complete nucleotide units. Conformational preferences and relative flexibilities are reported for various combinations of the roll, tilt, twist, lateral displacement, and propeller twist of individual residues. The predictions are compared with relevant experimental measures of conformation and flexibility, where available. The energy surfaces are found to fit into two distinct categories, some dimer duplexes preferring to bend in a symmetric fashion and others in a skewed manner. The effects of common chemical substitutions (uracil for thymine, 5-methyl cytosine for cytosine, and hypoxanthine for guanine) on the preferred arrangements of neighboring residues are also examined, and the interactions of the sugar-phosphate backbone are included in selected cases. As a first approximation, long range interactions between more distant neighbors, which may affect the local chain configuration, are ignored. A rotational isomeric state scheme is developed to describe the average configurations of individual dimers and is used to develop a static picture of overall double helical structure. The ability of the energetic scheme to account for documented examples of intrinsic B-DNA curvature is presented, and some new predictions of sequence directed chain bending are offered.

Base Composition↗
PubMed1984

Genome subunit reassortment among Bunyaviruses analysed by dot hybridization using molecularly cloned complementary DNA probes.

A simple and rapid procedure for determining the genotypes of viruses has been applied to analysis of genome subunit reassortment in heterologous crosses of Batai virus, Bunyamwera virus, and Maguari virus, three members of the Bunyamwera serogroup of bunyaviruses. The procedure for determining genotype made use of specific molecular probes to identify the parental origin of the L and M RNA subunits. Complementary DNA copies of the three RNA segments of Bunyamwera virus were prepared by reverse transcription using synthetic oligonucleotide primers for first and second strand synthesis. The cDNA transcripts were inserted into a pBR322 vector and gene-specific probes prepared from nick-translated plasmid DNA. L and M gene-specific probes were identified which could unequivocally discriminate Bunyamwera virus genome subunits in a dot-hybridization test using cytoplasmic RNA extracts immobilised on nitrocellulose filters. None of the S gene-specific probes were sufficiently discriminatory for use in this test. Instead the parental origin of the S RNA subunit was inferred from the electrophoretic mobility of the virion N protein. It was observed that reassortment did not occur at random in heterologous crosses of is mutants of the three viruses, and only the M RNA subunit appeared to segregate freely. However, unrestricted reassortment was observed when recombinant viruses with nonhomologous subunit combinations were used as the parental viruses. It was concluded, therefore, that restriction was mediated at the gene product level and that nonrandom reassortment was not due to incompatibility of genome subunits.

Animals↗
PubMed1984

Lentigo maligna melanoma has no better prognosis than other types of melanoma.

We studied 48 patients with lentigo maligna melanoma (LMM) and compared the clinical stage I patients with non-LMM melanoma patients (matched by site and thickness) to see if prognosis differed. There was no significant difference in mortality from melanoma between the two groups (P = .68) after a mean follow-up time of five years (67.5 months for LMM, 60.5 months for non-LMM). In addition, a Cox multivariate analysis of the entire matched group showed that only thickness was significantly associated with death from melanoma (P = .0007) while histology (LMM v non-LMM) did not make a significant contribution (P = .61). Our data suggest that after accounting for primary tumor thickness and site, LMM and non-LMM have the same prognosis and biologic behavior, in contrast to the widely held belief that LMM has a better prognosis than other forms of melanoma.

Actuarial Analysis↗
PubMed1983

Prospective study of alcoholism treatment. Eight-year follow-up.

One hundred patients admitted for alcohol withdrawal were followed for eight years. At the eight year mark, 25 percent had achieved stable abstinence of three years' duration or more, and 29 percent had died. Only 26 percent experienced continued serious problems with alcohol. Premorbid social stability and sustained abstinence made independent contributions to good psychosocial outcome at eight years. Premorbid social stability and Alcoholics Anonymous attendance made independent contributions to sustained abstinence. Review of these data and other major longitudinal studies suggests that factors other than professionally organized treatment per se exert substantial effect upon long-term outcome.

Alcoholism↗
PubMed1983

The independence of insulin release and ambient insulin in vitro.

The effect of insulin on its own secretion was tested in three independent experimental models using insulin concentrations that approached physiologic values. The collected secretions from glucose-stimulated islet tissue had no effect on insulin release from other islets. Perifused insulin had no effect on the release of endogenous insulin even when the assay was completely controlled for dilutional effects. Perifused insulin had no effect on the release of prelabeled insulin from glucose-stimulated islets. Similarly, proinsulin did not affect insulin release. Porcine insulin did not affect the function of porcine or canine islets. These studies strongly support the independence of glucose-stimulated insulin secretion and ambient insulin.

Animals↗
PubMed1982

A common role for target cell histocompatibility antigens in both nonspecific and specific T lymphocyte-mediated cytolysis.

We have investigated the role of target cell major histocompatibility complex antigens (MHC-Ag) in nonspecific lectin-dependent lymphocyte-mediated cytolysis (LDCC). In contrast to previous reports, we provide evidence that in LDCC the lectin Concanavalin A (Con A) does not mediate lysis by simply bridging cytotoxic T lymphocytes (CTL) and targets via cell surface sugars or by activating the lytic function of CTLs attached to targets via the lectin. Lysis occurs when target cells are pretreated with lectin, but not when CTL are pretreated. Moreover, when CTL populations are used as both aggressors and targets, and only one is pretreated with lectin, lysis occurs only in the direction of the pretreated CTL target. We have observed that LDCC, as in specific CTL-mediated killing, target recognition proceeds through interaction of CTL receptors (distinct from sugar moieties) and target cell surface determinants perhaps modified by, but distinct from, the lectin itself. We present evidence that the target determinants recognized in LDCC are MHC-Ag: 1) Cells that display reduced amounts of MHC-Ag are poor targets in LDCC; 2) removal of MHC-Ag by papain renders targets refractory to LDCC, however susceptibility is regained upon regeneration of MHC-Ag; and 3) antisera to target cell MHC-Ag block LDCC. The latter finding is also observed in oxidation-dependent CTL-mediated cytotoxicity. Involvement of MHC proteins in both specific and nonspecific CTL-mediated lysis reconciles an apparent fundamental distinction between these two processes and suggests a possible role for MHC proteins in a postrecognition step(s) leading to lysis.

Animals↗
PubMed1980

Membrane structure-function relationships in cell-mediated cytolysis. I. Effect of exogenously incorporated fatty acids on effector cell function in cell-mediated cytolysis.

The fatty acid composition of the membrane phospholipids of CTL memory cells restimulated with Con A can be altered significantly when selected exogenous fatty acids are present during the restimulation culture period. Such alterations also lead to significant changes in the subsequent cytolytic capacity of the regenerated CTL. Unsaturated fatty acids increase cytotoxicity, whereas saturated fatty acids lead to decreased cytotoxic function. The kinetics of the fatty acid effect on CTL function is the same as the kinetics of fatty acid incorporation into membrane phospholipids, suggesting that alteration of cytotoxicity results from altering membrane phospholipid fatty acid composition. The initial studies reported here suggest that this effect is mediated at the level of individual CTL, rather than through an alteration of CTL frequency in effector cell populations. Moreover, it seems unlikely that the fatty acids mediate their effect by altering membrane fluidity.

Amino Acids↗
PubMed1980

The social system of age group swimming: the perceptions of swimmers, parents and coaches.

The opinions of swimmers, parents and coaches on the social aspect of age group swimming indicate a unanimity of opinion on the value of this activity in the community. Nevertheless a majority of all subgroups thought some changes in its structure should take place. Principally more "fun" should mark both games and practices, heavy training and competition should be deemphasized while current motivational techniques and learning principles should be learned and observed by coaches.

Age Factors↗
PubMed1979

A rapid method for generating cytotoxic effector cells in vivo.

A method is described for the production of highly cytotoxic effector T lymphocytes. The cells can be raised in vivo in healthy animals in 4--5 days, thus combining the short time period of sensitization obtained in MLC or radiation GVH, without any of the attendant risks of these two methods (infection or loss of cultures or animals). DNA synthesis and blastogenesis are maximal 4 days after sensitization and are insignificant by day 6. 20--30% of the effector cells from conjugates with the sensitizing cell strain on days 4 through 7. Cytotoxicity was specific for cells of the sensitizing strain; blast cells are cytotoxic at the peak of the reaction (day 4) but small lymphocytes are cytotoxic on subsequent days.

Animals↗
PubMed1979

The application of Kelly's Repotory Grid Technique to investigate disabled people's perceptions of their professional workers.

Blaxter, (1976), has shown that there is an amount of confusion and misunderstanding of British medical and social services among disabled people. This study attempts to explore the perceptions of just two young disabled women to ascertain their individual views of what is seemingly a very complex array of services. No attempt has been made to generalise the findings, although future work, using group data, may be completed at a later date. The main objective of the study was to find out if Kelly's Repertory Grid Technique could be applied to this particular problem. The technique was used alongside indepth interviews. In general, the grid analysis did concur with the content analysis of the indepth interviews, particularly if the subject used her own elicited constructs. Both informal and formal agents of help were investigated, but due to lack of space, only the analyses of the three formal agents are permitted. In both case studies, the subjects' perceptions of each formal agent varied according to her attitude towards that agent and the experiences she had in dealing with him. This was verified by comparing the relationship between constructs and elements (agents) with the discriptions given during the indepth interviews. By using McQuitty's, (1960), elementary linkage analysis, two main clusters of agents were obtained. Inclusion within either cluster was largely dependant upon whether the subject considered the agent to be an authoritarian, or peer-like figure. A number of possible applications of the reportory grid technique, for future research, are also discussed.

Adult↗