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Biomedical subjects

Mark Evans

Publications and source records attributed to Mark Evans.

13 recordsLinked to original sources
PubMed2007

Chronic hexosamine flux stimulates fatty acid oxidation by activating AMP-activated protein kinase in adipocytes.

The hexosamine biosynthesis pathway (HBP) serves as a nutrient sensor and has been implicated in the development of type 2 diabetes. We previously demonstrated that fatty acid oxidation was enhanced in transgenic mouse adipocytes, wherein the rate-limiting enzyme of the HBP, glutamine:fructose-6-phosphate amidotransferase (GFA), was overexpressed. To explore the molecular mechanism of the HBP-induced fatty acid oxidation in adipocytes, we studied AMP-activated protein kinase (AMPK), an energy sensor that stimulates fatty acid oxidation by regulating acetyl-CoA carboxylase (ACC) activity. Phosphorylation and activity of AMPK were increased in transgenic fat pads and in 3T3L1 adipocytes treated with glucosamine to stimulate hexosamine flux. Glucosamine also stimulated phosphorylation of ACC and fatty acid oxidation in 3T3L1 adipocytes, and these stimulatory effects were diminished by adenovirus-mediated expression of a dominant negative AMPK in 3T3L1 adipocytes. Conversely, blocking the HBP with a GFA inhibitor reduced AMPK activity, ACC phosphorylation, and fatty acid oxidation. These changes are not explained by alterations in the cellular AMP/ATP ratio. Further demonstrating that AMPK is regulated by the HBP, we found that AMPK was recognized by succinylated wheat germ agglutinin, which specifically binds O-GlcNAc. The levels of AMPK in succinylated wheat germ agglutinin precipitates correlated with hexosamine flux in mouse fat pads and 3T3L1 adipocytes. Moreover, removal of O-GlcNAc by hexosaminidase reduced AMPK activity. We conclude that chronically high hexosamine flux stimulates fatty acid oxidation by activating AMPK in adipocytes, in part through O-linked glycosylation.

3T3-L1 Cells↗
PubMed2006

MIB-1 and MCM-2 immunohistochemical analysis does not aid in identification of serrated colorectal polyps with abnormal proliferation.

We investigated the staining characteristics of serrated polyps with abnormal proliferation (SPAP) using MIB-1 and MCM-2 to determine if they could provide assistance in delineating SPAPs from traditional hyperplastic polyps (HPs). Using published morphologic criteria we reviewed H&E slides of 107 polyps from 80 patients. Thirty-nine (36.4%) polyps met the criteria for SPAP Within a given region, polyps in the transverse colon had the largest percentage of SPAPs (50.0%) followed by the right colon (40.9%). The majority of SPAPs (82.1%) and HPs (72.1%) showed MIB-1 staining confined to the basal third of the crypts. The majority of SPAPs (59.0%) and HPs (52.9%) showed MCM-2 staining extending into the apical third of the crypts. We do not recommend MIB-1 or MCM-2 staining to differentiate SPAPs from conventional HPs, since staining characteristics are not significantly different between the 2 groups, and frequent variable crypt staining within a given polyp is difficult to interpret.

Biomarkers, Tumor↗
PubMed2005

Crisis card following self-harm: 12-month follow-up of a randomised controlled trial.

No intervention has been shown to be effective in preventing repetition of self-harm. In the 6-month follow-up of a large randomised controlled trial, we previously reported no effectiveness of the provision of a card offering 24-h crisis telephone consultation on repetition of self-harm. However, there was a possible benefit among those presenting following a first episode (OR=0.64, 95% CI 0.34-1.22). Here we report the 12-month follow-up of the trial. The results confirm no overall benefit of the intervention (OR=1.19, 95% CI 0.85-1.67). Among those with a first episode of self-harm, the possible benefit of the intervention had diminished (OR=0.89, 95% CI 0.52-1.52), although a modest effect cannot be excluded.

Crisis Intervention↗
PubMed2005

Increase in international normalized ratio after smoking cessation in a patient receiving warfarin.

A 58-year-old man who was taking warfarin at a stable dosage was admitted to the hospital with a diagnosis of bacterial meningitis. Although he had previously been a smoker, after this admission, he decided to give up smoking. He was continued on his previous warfarin maintenance dosage when discharged, and his international normalized ratio (INR) soon began to climb substantially. When questioned, the patient reported no diet or lifestyle changes other than his smoking cessation. The patient's INR was stabilized at a warfarin dosage 23% lower than the maintenance dosage before he stopped smoking. This case report illustrates the potential for an interaction between warfarin and cigarette smoking and further suggests that the effect could be significant if a patient starts or stops smoking during warfarin therapy.

Anticoagulants↗
PubMed2004

"Who gets in?" Recruitment and screening processes of outpatient substance abuse trials.

A brief telephone-screening interview was conducted with 1759 callers seeking treatment for substance abuse at the Treatment Research Clinic (TRC) over a 16-month period. The purpose of this study was to examine the effectiveness of various recruitment methods in attracting eligible participants and to identify screening variables that characterized eligible and ineligible callers. Callers referred by friends and family were more likely to be eligible than callers from other referral sources. Callers seeking treatment for cocaine abuse who reported more severe alcohol/substance problems were more likely to be eligible for treatment protocols, while those with severe problems in other psychosocial areas (legal, medical, and psychiatric) were more often excluded. Alcohol- and nicotine-dependent callers reporting severe alcohol problems were more likely to be eligible but otherwise were not different from callers who were ineligible. The effectiveness of recruitment methods may not be the same for different types of substance use disorders. This study underscores the importance of having a sensitive screening assessment for recruiting a homogeneous yet representative sample for outpatient substance abuse clinical trials.

Adolescent↗
PubMed2004

Combined endodontic and surgical treatment of a three-rooted maxillary first premolar.

A case is reported in which endodontic treatment of a maxillary first premolar was complicated by the fact that the tooth had three roots. One of the roots was completely calcified and therefore could not be negotiated with endodontic files. There was a large periapical lesion associated with the tooth and this was surgically removed. During the surgical procedure a retrograde cavity was prepared on the calcified root using ultrasonic instruments and this was filled using Super EBA cement. Twelve months later the tooth was asymptomatic and the periapical tissues had completely healed.

Aged↗
PubMed2003

An encoded particle array tool for multiplex bioassays.

The detection of both gene function at the genomic scale and protein assays at a proteomic scale is developing into an essential tool in the discovery and development of new medicines. A wide variety of techniques have been used that allow the analyst to assess the information gathered from a SNP up to a fully developed immunoassay. Despite these advances, there remains an ongoing drive to keep the cost of research and development down to reduce the cost of bringing a new drug or diagnostic to market. The demand to carry out large-scale bioassay analysis using yet smaller reagent volume and at a very low cost per test is gaining much importance as seen in the growing need to perform multiplex bioassays. In this article, we describe an analytical system that is being developed to address such a need for multiplexing bioassays at a low, affordable cost providing a flexible alternative consumable to the current technologies. This novel system utilizes inexpensive fabricated polymeric material produced by standard MEMS technology, which allows the attachment, through a variety of coupling chemistries, of oligonucleotides, proteins, antibodies, and antigens. These can then be analyzed by simple scanning, with either a flow cytometer or a simple optical reader, providing a robust, sensitive microarray assay system.

Oligonucleotide Array Sequence Analysis↗
PubMed2003

Biology and evolution of cervical squamous intraepithelial lesions: a hypothesis with diagnostic prognostic implications.

Recent advances in the understanding of HPV-associated cervical squamous intraepithelial lesions, specifically with respect to HPV DNA integration into basal cervical epithelial cells, need to be incorporated into strategies for diagnosing and classifying these lesions. The biology and evolution of HPV-associated cervical squamous intraepithelial lesions is reviewed, along with recent developments using tyramide-based in situ hybridization and MIB-1 immunoreactivity. It is proposed that HPV DNA integration into the basal cells of cervical squamous epithelium precedes the transformation of low-into high-grade lesions. The HPV DNA tyramide-based in situ hybridization system may prove to be a powerful diagnostic/prognostic tool in this regard. It is also proposed that the presence of mitoses (especially atypical forms) in the upper layers may be a discriminatory hallmark in the morphologic distinction between low- and high-grade lesions. Further, since the biologic changes manifest between these two lesions are reflected in their respective phenotype, it appears plausible to adopt the Bethesda System two-tiered/binary classification of LGSIL and HGSIL for histopathologic diagnoses.

DNA, Neoplasm↗
PubMedDate not supplied

The expression of p21/WAF-1 and cyclin B1 mediate mitotic delay in x-irradiated fibroblasts.

BACKGROUND: To better understand the relationship between mitotic delay and the disruption of cyclin B1 and p21 in x-irradiated fibroblasts, studies were carried out to establish correlations between the downregulation of cyclin B1 by the cyclin kinase inhibitor (CKI) p21 and the induction of mitotic delay in the NIH3T3 fibroblast. MATERIALS AND METHODS: Cell cycle kinetics were used to analyze mitotic delay in irradiated NIH3T3 cells and immunocytochemistry incorporated to assess the expression of cyclin B1 and p21, following 2 or 4 Gy x-irradiation. RESULTS AND DISCUSSION: Results indicate a dose dependent increase in mitotic delay accompanied by a downregulation of cyclin B1 and corresponding upregulation of the CKI p21 in exponentially growing cultures. Data indicates that the induction of radiation-induced division delay appears to be dependent on the p21 inhibition of cyclin B1 and, furthermore, p21 and cyclin B1 expression are highly dependent on cell density.

Animals↗
PubMedDate not supplied

Correlations between radiation-induced double strand breaks and cell cycle checkpoints in X-irradiated NIH/3T3 fibroblasts.

BACKGROUND: To better understand the relationship between the formation of radiation-induced DNA double strand breaks (DSB) and cell cycle checkpoint activation, studies were conducted in the NIH/3T3 fibroblast cell line in order to establish correlations between the temporal appearance of gamma-H2AX foci (a DSB) and the expression of the cell cycle regulatory proteins, the cyclins, and their cyclin kinase inhibitor, p21. MATERIALS AND METHODS: Immunocytochemistry was used to determine the expression of cyclin E, A, B1, p21, and the generation of DSB in NIH/3T3 cells exposed to 2 or 4 Gy X-irradiation. RESULTS AND DISCUSSION: The data suggest that the G1/S- and S-phase delay (cyclin E and cyclin A protein levels) are dependent on the dose of radiation while the G2/M (cyclin B1 protein levels) delay is dependent on the quantity of DSB sustained by the irradiated cell.

Animals↗