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Biomedical subjects

M Kelleher

Publications and source records attributed to M Kelleher.

At least 19 recordsLinked to original sources
PubMed2000

Identification of the copper regulon in Saccharomyces cerevisiae by DNA microarrays.

In Saccharomyces cerevisiae, copper ions regulate gene expression through the two transcriptional activators, Ace1 and Mac1. Ace1 mediates copper-induced gene expression in cells exposed to stressful levels of copper salts, whereas Mac1 activates a subset of genes under copper-deficient conditions. DNA microarray hybridization experiments revealed a limited set of yeast genes differentially expressed under growth conditions of excess copper or copper deficiency. Mac1 activates the expression of six S. cerevisiae genes, including CTR1, CTR3, FRE1, FRE7, YFR055w, and YJL217w. Two of the last three newly identified Mac1 target genes have no known function; the third, YFR055w, is homologous to cystathionine gamma-lyase encoded by CYS3. Several genes that are differentially expressed in cells containing a constitutively active Mac1, designated Mac1(up1), are not direct targets of Mac1. Induction or repression of these genes is likely a secondary effect of cells because of constitutive Mac1 activity. Elevated copper levels induced the expression of the metallothioneins CUP1 and CRS5 and two genes, FET3 and FTR1, in the iron uptake system. Copper-induced FET3 and FTR1 expression arises from an indirect copper effect on cellular iron pools.

Carrier Proteins↗
PubMed2000

Functional independence of the two cysteine-rich activation domains in the yeast Mac1 transcription factor.

Mac1 is a transcriptional activator whose activity is inhibited by copper ions. Mutagenesis studies were carried out to map residues important in the copper inhibition of Mac1 activity. Seven new missense mutations were identified that resulted in copper-independent Mac1 transcriptional activation. All seven mutations were clustered in one of two C-terminal cysteine-rich motifs, designated the C1 motif. All but one of the constitutive Mac1 mutations occurred in one of the conserved six residues in the (264)CXC[(X)(4)]CXC[(X)(2)]C[(X)(2)][H(279)]C1 motif. The lone exception was a L260S substitution. Two additional MAC1 mutations exhibiting constitutive activity were in-frame deletions encompassing portions C1. Engineered mutations in the second cysteine-rich motif did not yield a constitutively active Mac1. These results are consistent with the C1 motif being the copper-regulatory switch. Both cysteine-rich motifs exhibited transactivation activity, although the C1 activator was weak relative to the C2 activator. Limited copper metalloregulation of Mac1 was observed with only the C1 activator fused to the N-terminal DNA binding domain. Thus, the two Cys-rich motifs appear to function independently. The C1 motif appears to be a functional copper-regulatory domain.

Amino Acid Sequence↗
PubMed2000

Clinical evaluation of resin-bonded gold alloy veneers.

STATEMENT OF PROBLEM: Clinical performance of resin-bonded alumina-abraded type III cast gold alloy veneers has not been reported. PURPOSE: This retrospective study evaluated the survival of such restorations for the management of tooth wear and other restorative problems. MATERIAL AND METHOD: This clinical study evaluated 25 patients between 14 and 60 years of age treated with a total of 158 cast gold veneers cemented with Panavia Ex cement. Restorations placed between January 1990 and February 1996 (mean age 48 months) were evaluated. Factors, including age, gender, operator, site, design, the extent of dentin exposure, the presence of previous restorations, dynamic and static occlusion, rubber dam, cause, and methods of interocclusal space creation, were evaluated with Cox regression. Survival probability was evaluated with Kaplan-Meier analyses. Significance was taken as P <.05. RESULTS: Failures occurred for 7.6% of restorations in 28% of patients. Alumina-abraded gold alloys cemented with Panavia Ex cement had an estimated 89% survival probability at 60 months using Kaplan-Meier analyses. The only variable to statistically influence survival was operator (P <.0001). Operator differences were due to a single operator who placed only 2 restorations in the same patient, both of which failed unusually quickly. CONCLUSION: Resin-bonded alumina-abraded type III cast gold alloys can be successfully used to restore both anterior and posterior teeth and were associated with an estimated 89% survival probability at 60 months.

Adolescent↗
PubMed1998

Transient expression of beta-galactosidase in differentiating sporozoites of Eimeria tenella.

A transient transfection system has been developed for a member of the Apicomplexa, Eimeria tenella, using beta-galactosidase (betagal) from Escherichia coli as the reporter enzyme. Successfully expressed constructs contained sequences of the E. tenella microneme gene Etmic-1 fused to the coding region of lacZ. Transfectants expressing betagal were able to invade host cells and proceed through part of the life-cycle, forming schizonts from which merozoites were released. This indicated that transfectants could differentiate at least to first generation schizonts. However, this differentiation was delayed compared with unelectroporated sporozoites by approximately 15 h. Some merozoites arising from transfected sporozoites also expressed betagal. These results are encouraging for the development of a stable transfection system for E. tenella, using betagal as a reporter enzyme.

Animals↗
PubMed1998

Young adult patients with established dental erosion--what should be done?

This clinical paper discusses the problem of managing established erosion in the young patient. For a significant number of these patients it is not possible to establish conclusively the erosive source. Intermediate composite restorations, in addition to the use of normal preventive measures, can be used to protect eroded teeth from further damage. The main goal of such restorations is to protect the viability of the worst-affected teeth until such time as the aetiological factors can be identified and controlled. They can also improve overall aesthetics and create interocclusal space.

Adolescent↗
PubMed1997

Wear now? An update on the etiology of tooth wear.

Tooth wear is an ever-increasing problem, and younger patients are particularly at risk. The problem is likely to continue as patients' demands and expectations rise and as more natural teeth are retained into old age. The etiology of tooth wear is reviewed, with emphasis on those factors that appear to be major contributors to the problem at the moment. The clinical appearance of tooth wear is also discussed. It would appear that erosive factors are a significant cause of tooth wear. The prominence of acidic damage of tooth tissue is probably a reflection of society's concern with healthy eating and appearance.

Humans↗
PubMed1997

The aetiology and clinical appearance of tooth wear.

This paper highlights the importance of recognising that tooth wear has invariably a multifactorial aetiology, although the clinical appearance may suggest a single contributory factor. Failure to do so may lead to continued loss of tooth tissue and ultimate failure in restorative care. The possible aetiological factors are highlighted and suggestions as to the cause of the increasing problem are discussed.

Beverages↗
PubMed1996

Margin design for porcelain fused to metal restorations which extend onto the root.

A 90 degree shoulder is probably the most commonly used margin design for porcelain fused to metal (PFM) restorations. However, this design requires the removal of a significant amount of tooth tissue to provide a predictable restoration. This increases the risk of irreversible damage to the pulp, particularly if little tooth tissue is present, for example on exposed roots. In these situations more conservative designs, such as the 135 degree shoulder or deep chamfer, should be considered. Ideally these designs should be used with an all-metal margin since this is associated with the most predictable marginal seal. Where an all metal margin is aesthetically unacceptable a porcelain butt or subgingival margin can be considered. Newer techniques, such as resin bonded crowns, which minimise tooth destruction and provide acceptable aesthetics may be a viable alternative to traditional PFM restorations. Unfortunately, these newer techniques have not been evaluated long-term.

Crowns↗
PubMed1996

Restoration of a worn dentition using a double-veneer technique.

Restoration of dentitions affected by tooth surface loss has been a problem to the dental profession for many years. This problem is likely to increase as the population ages and retains more teeth into old age. This article describes a method of restoring teeth with non-carious loss of tooth tissue whilst conserving the remaining tooth tissue.

Aged↗
PubMed1996

Oral complications associated with sickle cell anemia: a review and case report.

Sickle cell anemia is a multisystem disease that can affect the oral region. This article reviews previously reported oral complications associated with this disease and describes the cause of these problems. A case history describes a patient with multiple oral problems after a sickle cell crisis. The diagnostic and management problems of this case are highlighted. The need for a multidisciplinary approach to the care of these patients is emphasized.

Acute Disease↗
PubMed1995

IASP task force on euthanasia and assisted suicide.

The first meeting of the IASP Task Force on Euthanasia and Assisted Suicide took place in Venice on June 7, 1995. Several interested observers were present. It was decided that at the public IASP meeting the following day each speaker should address, briefly, the current legal situation and the pressure for change, as well as give a personal statement. David Clark spoke for North America, Bob Goldney for Australia, Michael Kelleher for Britain and Ireland, Jerzy Wasserman for Scandinavia, and Hans Wedler for the German-speaking world. Their views are published in this article. Ad Kerkhof requested that the Dutch television film "Death on Request" be discussed. The committee was of the opinion that clear definitions were essential. In their view, these should take into account the differences between active and passive euthanasia, as well as between professionally assisted and lay-assisted suicide.

Australia↗
PubMed1995

Sickle cell disease: a diagnostic dilemma.

The case history is described of a patient with sickle cell anaemia who developed a unilateral infarct of the mandible following a sickle cell crisis. The interruption of the blood supply resulted in an anaesthesia of the inferior dental nerve and pulpal necrosis of otherwise sound premolar and molar teeth. The diagnostic and management difficulties of the case are discussed, and recommendations are made for treatment of such patients in light of the problems encountered.

Acute Disease↗
PubMed1995

Lipophosphoglycan blocks attachment of Leishmania major amastigotes to macrophages.

Promastigotes of the intracellular protozoan parasite Leishmania major invade mononuclear phagocytes by a direct interaction between the cell surface lipophosphoglycan found on all Leishmania species and macrophage receptors. This interaction is mediated by phosphoglycan repeats containing oligomers of beta (1-3)Gal residues specific to L. major. We show here that although amastigotes also use lipophosphoglycan to bind to both primary macrophages and a cell line, this interaction is independent of the beta (1-3)Gal residues employed by promastigotes. Binding of amastigotes to macrophages could be blocked by intact lipophosphoglycan from L. major amastigotes as well as by lipophosphoglycan from promastigotes of several other Leishmania species, suggesting involvement of a conserved domain. Binding of amastigotes to macrophages could be blocked significantly by the monoclonal antibody WIC 108.3, directed to the lipophosphoglycan backbone. The glycan core of lipophosphoglycan could also inhibit attachment of amastigotes, but to a considerably lesser extent. The glycan core structure is also present in the type 2 glycoinositolphospholipids which are expressed on the surface of amastigotes at 100-fold-higher levels than lipophosphoglycan. However, their inhibitory effect could not be increased even when they were used at a 300-fold-higher concentration than lipophosphoglycan, indicating that lipophosphoglycan is the major macrophage-binding molecule on amastigotes of L. major. In the presence of complement, the attachment of amastigotes to macrophages was not altered, suggesting that lipophosphoglycan interacts directly with macrophage receptors.

Animals↗
PubMed1994

Palatal inlays.

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Composite Resins↗