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Biomedical subjects

J A Cunningham

Publications and source records attributed to J A Cunningham.

At least 37 records · Page 2Linked to original sources

DNA adducts of 2,3-epoxy-4-hydroxynonanal: detection of 7-(1', 2'-dihydroxyheptyl)-3H-imidazo[2,1-i]purine and 1,N6-ethenoadenine by gas chromatography/negative ion chemical ionization/mass spectrometry.

2,3-Epoxy-4-hydroxynonanal (EH) is a bifunctional aldehyde formed by epoxidation of trans-4-hydroxy-2-nonenal, a peroxidation product of omega-6 polyunsaturated fatty acids. EH is mutagenic and tumorigenic and capable of modifying DNA bases forming etheno adducts in vitro. Recent studies showed that etheno adducts are present in tissue DNA of humans and untreated rodents, suggesting a potential endogenous role of EH in their formation. A sensitive assay is needed so we can determine whether EH is involved in etheno adduct formation in vivo and study the biological significance of the etheno adducts in DNA. In this study, we developed a gas chromatography/negative ion chemical ionization/mass spectrometry assay for the analysis of 1, N6-ethenoadenine (epsilonAde) and 7-(1', 2'-dihydroxyheptyl)-3H-imidazo[2,1-i]purine (DHH-epsilonAde) in DNA; both are products from the reaction of adenine with EH. The assay entails the following sequence of steps: (1) addition of [15N5]epsilonAde and [15N5]DHH-epsilonAde to DNA as internal standards, (2) acid hydrolysis of DNA, (3) adduct enrichment by C18 solid phase extraction (SPE), (4) derivatization by pentafluorobenzylation (PFB), (5) separation of PFB-epsilonAde and PFB-DHH-epsilonAde on a Si SPE column, (6) acetonide (ACT) formation of PFB-DHH-epsilonAde, and (7) GC/MS analysis with selective ion monitoring (SIM). The limit of detection by on-column injection for PFB-epsilonAde monitoring of the (M - PFB)- ion at m/z 158 was 30 amol and for ACT-PFB-DHH-epsilonAde monitoring of the (M - PFB)- ion at m/z 328 was 0.4 fmol; the detection limits for the entire assay were 6.3 fmol for epsilonAde and 36 fmol for DHH-epsilonAde. In calf thymus DNA modified with EH at 37 degreesC for 50 h, both epsilonAde and DHH-epsilonAde were detected at high levels by this method, 4.5 +/- 0.7 and 90.8 +/- 8.7 adducts/10(3) adenine, respectively. These levels were also verified by HPLC fluorescence analysis, indicating that EH extensively reacts with adenine in DNA, forming etheno adducts. The high sensitivity of the assay suggests that it may be used in the analysis of ethenoadenine adducts in vivo.

Adenine↗

A social marketing model for disseminating research-based treatments to addictions treatment providers.

AIMS: Researchers must develop effective strategies for disseminating research-based treatments. This study evaluates the application of a dissemination model based on principles of social marketing and diffusion theory. DESIGN: A case study describes how the model was implemented. A qualitative design was employed to examine rates of adoption and adaptation of an early intervention program by a targeted system of addictions agencies. SETTING: The interventions were developed at the Addiction Research Foundation in Toronto and disseminated to Assessment and Referral (A/R) Centres in Ontario, Canada. PARTICIPANTS: Study participants included the managers and a designated therapist for 33 participating A/R centres. MEASUREMENTS: Managers were asked mainly open-ended questions concerning whether their agency had made a formal decision to adopt the intervention and whether therapists in their agency were using the early intervention program. "Adoption" was operationalized as offering the complete four-session intervention to at least one client. FINDINGS: At 12 months after the completion of training workshops, 68% of 34 agencies in the target system had adopted the program while 85% of the agencies were using some components of the intervention with clients. CONCLUSIONS: The dissemination model appeared to be effective although its application proved to be time-consuming and labour-intensive. The "market analysis", systems focus and field-test components of the model appeared to contribute to its success.

Delivery of Health Care↗

Effects of localized auditory information on visual target detection performance using a helmet-mounted display.

An experiment was conducted to evaluate the effects of localized auditory information on visual target detection performance. Visual targets were presented on either a wide field-of-view dome display or a helmet-mounted display and were accompanied by either localized, nonlocalized, or no auditory information. The addition of localized auditory information resulted in significant increases in target detection performance and significant reductions in workload ratings as compared with conditions in which auditory information was either nonlocalized or absent. Qualitative and quantitative analyses of participants' head motions revealed that the addition of localized auditory information resulted in extremely efficient and consistent search strategies. Implications for the development and design of multisensory virtual environments are discussed. Actual or potential applications of this research include the use of spatial auditory displays to augment visual information presented in helmet-mounted displays, thereby leading to increases in performance efficiency, reductions in physical and mental workload, and enhanced spatial awareness of objects in the environment.

Adult↗

Echovirus 1 interaction with the human very late antigen-2 (integrin alpha2beta1) I domain. Identification of two independent virus contact sites distinct from the metal ion-dependent adhesion site.

The human integrin very late antigen (VLA)-2 (CD49b/CD29) mediates interactions with collagen and is the receptor for echovirus 1. Binding sites for both collagen and echovirus 1 have been mapped to the I domain within the alpha2 subunit of the VLA-2 alpha2beta1 heterodimer. Although murine VLA-2 interacts with collagen, it does not bind virus. We have used isolated human-murine chimeric I domains expressed as glutathione S-transferase fusion proteins in Escherichia coli to identify two groups of amino acids, 199-201 and 212-216, independently involved in virus attachment. These residues are distinct from the metal ion-dependent adhesion site previously demonstrated to be essential for VLA-2 interactions with collagen. Mutations in three metal ion-dependent adhesion site residues that abolish adhesion to collagen had no effect on virus binding. These results confirm that different sites within the I domain are responsible for VLA-2 interaction with extracellular matrix proteins and with viral ligands.

Amino Acid Sequence↗

Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5.

A complementary DNA clone has been isolated that encodes a coxsackievirus and adenovirus receptor (CAR). When transfected with CAR complementary DNA, nonpermissive hamster cells became susceptible to coxsackie B virus attachment and infection. Furthermore, consistent with previous studies demonstrating that adenovirus infection depends on attachment of a viral fiber to the target cell, CAR-transfected hamster cells bound adenovirus in a fiber-dependent fashion and showed a 100-fold increase in susceptibility to virus-mediated gene transfer. Identification of CAR as a receptor for these two unrelated and structurally distinct viral pathogens is important for understanding viral pathogenesis and has implications for therapeutic gene delivery with adenovirus vectors.

Adenoviruses, Human↗

Clinical coxsackievirus B isolates differ from laboratory strains in their interaction with two cell surface receptors.

Coxsackie B viruses interact with two putative cell surface receptor molecules. Experiments with prototype laboratory strains suggest that all 6 coxsackie B serotypes interact with a 46-kDa protein recognized by the monoclonal antibody RmcB, whereas CB1, CB3, and CB5 may also bind to decay accelerating factor. Antireceptor monoclonal antibodies were used to study interactions between low-passage clinical coxsackie B virus isolates and the two receptors. In contrast to observations made with single prototype strains, these data indicate that receptor use by clinical isolates is not strictly related to serotype and that even prototype strains with different passage histories may differ in receptor use. Within a given serotype, variation exists in the capacity of individual virus isolates to bind to specific receptors, and variants with altered receptor specificity may arise during infection in humans and in tissue culture.

Antibodies, Monoclonal↗

Toward a stepped care approach to treating problem drinkers: the predictive utility of within-treatment variables and therapist prognostic ratings.

AIMS: Cost containment, a central issue in current health planning, encourages the use of brief interventions. Although brief interventions for problem drinkers have proved successful, a portion of such individuals do not change their alcohol use during treatment. DESIGN: Repeated measures design (pre-treatment, within-treatment and 6 months post-treatment). SETTING AND PARTICIPANTS: To identify individuals at risk for continued problem drinking, predictors of post-treatment drinking were examined for 212 problem drinkers who presented for treatment in an outpatient treatment clinic. INTERVENTION: All participants completed a brief cognitive behavioral motivational intervention. MEASUREMENTS: At the pre-treatment assessment demographic, drinking pattern, severity of dependence and other cognitive variables (e.g. self-efficacy, goal choice) were collected. Within-treatment, drinking pattern and cognitive variables such as self-efficacy and goal choice were again measured. FINDINGS: Regression analyses showed that therapist prognosis ratings contributed significantly to the prediction of outcome even when pre-treatment variables were controlled. However, when within-treatment variables were included in the prediction, variables such as within treatment drinking eliminated the predictive utility of therapist prognosis ratings. This pattern held for both percentage of days abstinent and drinks per drinking day at a 6-month follow-up. CONCLUSIONS: It is suggested that a stepped care approach based on prediction models that include clients' within-treatment response can be applied to the treatment of problem drinkers who show little initial response to treatment.

Adult↗

Xanthogranulomatous pyelonephritis in a pregnant woman: a case report and review of the literature.

We report a rare case of a 24-year-old woman who presented during her second trimester of pregnancy with a presumptive diagnosis of right-sided xanthogranulomatous pyelonephritis (XGP). Despite attempted conservative management, the patient ultimately required a right nephrectomy without complications to either the patient or fetus. Pathology confirmed the diagnosis of XGP of the right kidney. Herein, we present a case report and a review of the literature concerning XGP and pregnancy.

Adult↗

Recovery from alcohol problems with and without treatment: prevalence in two population surveys.

OBJECTIVES: The purpose of this study was to determine the prevalence of recovery from alcohol problems with and without treatment, including whether such recoveries involved abstinence or moderate drinking. METHODS: Data from two surveys of randomly selected adults in the general population were analyzed. Random-digit dialing was used to conduct telephone interviews with 11,634 and 1034 respondents. Respondents 20 years of age or older were categorized on the basis of drinking status and history. RESULTS: Both surveys found that most individuals (77.5% and 77.7%) who had recovered from an alcohol problem for 1 year or more did so without help or treatment. A sizable percentage (38% and 63%) also reported drinking moderately after resolving their problem. CONCLUSIONS: These two surveys are among the first to report prevalence rates for recovery from alcohol problems for treated and untreated individuals and for moderation and abstinence outcomes.

Adult↗

Resolution from alcohol problems with and without treatment: reasons for change.

Volunteers at a local science center were asked their reasons for quitting or reducing their alcohol consumption. Of 248 respondents, 64 were classified as having had an alcohol problem from which they had successfully resolved for 1 or more years. Three quarters of all respondents resolved without treatment or self-help groups, and over half (57.8%, 37 of 64) of these respondents' resolutions involved nonabstinence (i.e., moderate drinking). The reason for resolution most often endorsed by respondents was that they had "weighed the pros and cons of drinking and not drinking." The implications of these findings for intervention programs are discussed.

Adult↗

Echovirus 1 interaction with the isolated VLA-2 I domain.

The isolated I domain of the integrin VLA-2, produced as a bacterial fusion protein, specifically bound echovirus 1 and prevented virus attachment to cells. These results demonstrate that the receptor structures critical for virus attachment are contained solely within the VLA-2 I domain and that soluble receptor fragments are capable of preventing infection.

Animals↗

Infant pyeloplasty is a low-risk procedure.

Early pyeloplasty for the treatment of congenital ureteropelvic junction obstruction to maximize nephron salvage is only justified if the potential hazards of operating on small infants are avoided. The records of all infants who underwent pyeloplasty by the authors over a 7-year period were analyzed. The outcome of surgery in the younger infant group (YIG; patients less than 2 months of age) was compared with that of the older infant group (OIG; patients more than 2 months of age). Preoperative evaluation in cases of mild or moderate hydronephrosis was directed toward ruling out a nonobstructed collecting system and included voiding cysto-urethrography and serial ultrasonography and/or dual isotope diuretic renography. Open pyeloplasty was performed if collecting systems had deteriorated or were demonstrated to be obstructed; it was also performed for severe cases of hydronephrosis. Postoperative assessment consisted of serial ultrasonography and/or nuclear imaging to confirm decompression and relief of obstruction. Thirty three pyeloplasties were performed in 31 patients in the YIG (two bilateral), and 33 were performed in 32 infants in the OIG (one bilateral). The only significant differences between the groups were as follows. Patients in the YIG were more likely to present in utero (87% v 53%; P < .01), whereas those in the OIG were more likely to present with a urinary tract infection (44% v 0%; P < .01). The YIG was more likely to have nephrostomy drainage postoperatively (67% v 45%; P < .01). In the overall series, there were five complications, all of which were postoperative infections requiring intravenous antibiotic therapy. Two occurred in the YIG and three in the OIG.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Metastatic malignant melanoma: an unusual case presentation.

Secondary involvement of the genitourinary tract with malignant melanoma is a common autopsy finding, but rarely evident clinically. We report a rare case involving a previously asymptomatic patient presenting with gross hematuria and a large renal mass, which was found to be metastatic melanoma. We propose that metastatic melanoma to the kidney, although rare, be considered in the differential diagnosis of disease processes causing hematuria.

Adult↗

Beliefs about the causes of substance abuse: a comparison of three drugs.

Respondents were randomly assigned to one of three conditions and completed a questionnaire asking about their beliefs regarding the causes of alcohol abuse, cocaine abuse, or cigarette smoking, and about their humanitarian attitudes toward substance abusers. Three major findings emerged: (a) compared to the other substances of abuse, the disease concept was most strongly endorsed for alcohol abuse, the sin conception for cocaine abuse, and the habit conception for smoking; (b) for alcohol abuse only, endorsement of the disease concept was positively related to humanitarian attitudes; and (c) for all three substance types, the sin conception was negatively related to the expression of humanitarian attitudes. Implications of these findings are discussed.

Adult↗

What's in a label? The effects of substance types and labels on treatment considerations and stigma.

Visitors (N = 579) to a science center read selected scenarios and evaluated the most likely outcome for a hypothetical substance abuser. Respondents were randomly assigned to one of six scenario conditions: a person with one of three different substance abuse problems (alcohol, tobacco, or cocaine) was crossed with two labels reflecting high or low substance dependence. Results indicated that: (1) cigarettes were viewed as a less serious substance abuse problem than were alcohol or cocaine (a person who smoked cigarettes was rated as more likely to recover from his problem, self-change was regarded as more appropriate and less stigma was associated with smoking than with the other two drugs); (2) non-abstinent recoveries of all types were greeted with skepticism; and (3) recovery was rated as more likely to occur from treatment than from self-change.

Adaptation, Psychological↗

Docking of dogs.

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Animals↗

A relationship between perceived self-efficacy and quality of life in cancer patients.

The quality of life of cancer patients may be influenced by the degree of control they feel able to exert over stressful situations arising from having the disease. We were able to test this association using a newly developed instrument, the Stanford Inventory of Cancer Patient Adjustment which assesses perceived self-efficacy, that is, perceived ability to enact coping strategies. In a heterogeneous sample of 273 cancer patients a strong positive correlation was found between self-efficacy and quality of life and between self-efficacy and mood. Improvements in all three measures brought about by a brief, group program teaching coping skills were also highly correlated. By contrast, no significant association was seen between improvement in mood or quality of life and amount of home practice of coping skills.

Adaptation, Psychological↗