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R Kennedy

Publications and source records attributed to R Kennedy.

At least 37 records · Page 2Linked to original sources
PubMed1999

Glutamine protects against doxorubicin-induced cardiotoxicity.

UNLABELLED: Doxorubicin (DOX) dose-intensive therapy for breast cancer is limited by a cardiomyopathy that often results in overt congestive heart failure. We hypothesized that dietary glutamine (GLN) can diminish DOX-induced cardiotoxicity by maintaining tissue glutathione (GSH) levels and thus preventing the proposed mechanism of cardiac injury: oxidation. METHODS: Forty-two female Fisher 344 rats were randomized into one of six groups: GLN + saline (SAL), GLN + DOX, freamine (FA) + SAL, FA + DOX, H2O + SAL, and H2O + DOX. Rats were pair-fed chow and gavaged with 1 g/kg/day GLN or an isonitrogenous amount of FA or H2O for 28 days. Rats were injected intravenously with a single dose of SAL or 9 mg/kg DOX on day 7 of gavage. At 28 days (21 days post-DOX), rats were sacrificed and blood and cardiac tissue were assayed for GLN and GSH content and lipid peroxidation (LP). RESULTS: There were no differences in cardiac GSH levels and cardiac lipid peroxidation in GLN + SAL versus GLN + DOX groups. However, blood and cardiac GSH levels were significantly decreased in H2O + DOX and FA + DOX groups compared to controls (H2O + SAL and FA + SAL). CONCLUSION: These data suggest that dietary GLN supplementation may diminish DOX-induced oxidative damage and thus cardiotoxicity through upregulation of cardiac GSH metabolism.

Animals↗
PubMed1999

Induction of antibody response by DNA immunization of newborn baboons against influenza virus.

Previous studies showed that DNA immunization of newborn mice with plasmids expressing influenza virus antigens induced protective immunity. We have now extended the study of neonatal responsiveness to DNA vaccines to nonhuman primates. Baboons immunized as neonates with plasmids expressing type A influenza virus hemagglutinin (HA) and nucleoprotein (NP) in doses ranging from 40 microg to 1 mg per plasmid per dose developed virus-specific humoral responses. The titer and kinetics of appearance of virus-specific IgG antibodies were dose dependent. Specific antibodies were detected by enzyme-linked immunosorbent assay (ELISA) as early as 1 month after birth in baboons immunized with the highest and intermediate doses of vaccine. Virus-neutralizing antibodies were detected in the group of baboons immunized with the highest dose. The specificity of virus-neutralizing antibodies was found to be directed against homologous determinants of HA; however, the IgG antibodies also cross-reacted with HA of a drift variant. Thus, DNA vaccination of newborn baboons with a prototype vaccine against influenza virus resulted in induction of specific humoral immunity.

Animals↗
PubMed1999

In times of transition: an organizational change from a family systems perspective.

This article reports on observations of the implementation of a patient-centered care (PCC) work reorganization model in a community hospital setting. Analysis of videotape, direct observation, and interviews with key informants demonstrated the similarities between organizations and families in times of change. We propose a family systems framework for understanding some of the complex relationships and transitional experiences we observed.

Family↗
PubMed1998

Fibronectin-binding activity in Borrelia burgdorferi1.

Recently, the term MSCRAMM (microbial surface components recognizing adhesive matrix molecules), has been introduced to describe microbial molecules that recognize extracellular matrix (ECM) [1]. Here we present evidence for the presence of fibronectin-binding molecules in Borrelia burgdorferi and several other Borrelia species. Immunofluorescence studies show that plasma fibronectin is bound uniformly over the cell surface of free swimming B. burgdorferi. In addition, the spirochetes are able to bind to plasma fibronectin-coated microwell plates, an interaction that is inhibited by anti-fibronectin antibody as well as exogenous plasma fibronectin. Taken together, the data suggest that fibronectin binds to the surface of the spirochete. On Western blot-like assays, B. burgdorferi and some B. afzelii strains express a major fibronectin-binding protein (Fn-BA) with an approximate molecular mass of 52 kDa. In addition, several other major Fn-BAs were found in B. hermsii (26, 31, 33, 39, 46, 54 and 58 kDa) and B. turicatae (39, 41, 45, 50, 56, 59 and 66 kDa). Preliminary evidence suggests that fibronectin (and Fn-BA) may play a role as a molecular bridge between the spirochete and other components of the extracellular matrix.

Adhesins, Bacterial↗
PubMed1998

Factors related to miles driven between drinking and arrest locations among convicted drunk drivers.

The objectives of the study were to estimate the distance driven between drinking and arrest locations among 3,107 offenders convicted of driving while impaired and to determined whether the drinking location, the driver's appearance (factors such as race, age, gender), or age of the vehicle account for any differences in the estimated distance driven. Statistical models were used to determine odds ratios for being arrested in the immediate vicinity of the drinking location, and for miles driven impaired. The independent sociodemographic and arrest variables included: age, gender, ethnicity/race, vehicle age, drinking location, whether the arrest followed a crash, time of arrest, blood alcohol concentration, and drinking in areas with varying levels of arrest intensity. The variables associated with arrest in the immediate vicinity of the drinking location (less than one half mile) were drinking in high or medium-high arrest intensity areas, Hispanic/Mexican ethnicity/nationality, Native American race, and drinking at home. Among those who were not arrested in the immediate vicinity, the number of miles driven ranged from 0.5 to 18.2, with a mean of 3.4 miles (median = 2.6). Analysis of covariance demonstrated that among those arrested outside the immediate vicinity of their drinking locations, persons who drank in a high or medium-high arrest intensity area, those with blood alcohol concentrations of > or = 200 mg/l, and those drinking at bars, restaurants, or private parties, drove fewer miles compared to other offenders. Our findings are mixed regarding ethnicity/race. Traits such as age, gender, and vehicle age are unrelated to how far drunk drivers travel before their arrests.

Adolescent↗
PubMed1998

Increased incidence of congenital malformations in children with transient thyroid-stimulating hormone elevation on neonatal screening.

We investigated the incidence of congenital malformation in all infants with raised thyroid-stimulating hormone (TSH) levels on neonatal screening in Scotland between August 1979 and December 1993. Of 344 infants with elevated TSH, 31 (9%) had one or more malformations: 12 cardiac 15 noncardiac, and 16 dysmorphic syndromes (including 5 with Down syndrome). Criteria were devised to distinguish between definite or probable congenital hypothyroidism and transient TSH elevation. Congenital hypothyroidism was considered definite in 224 (65.1%) infants and probable in 11 (3.2%). Eighty-eight (25.6%) infants had transient TSH elevation, whereas thyroid status was uncertain in 21 (6.1%). In the definite group 12 (5.4%) infants had one or more malformations compared with 13 (14.8%) in the transient group. Cardiac malformation, noncardiac malformation, dysmorphic syndromes, and "sickness" were much more frequent in the transient compared with the definite group: 5.7% versus 1.8%, 8.0% versus 1.8%, 6.8% versus 2.7%, and 37.5% versus 7.1%, respectively. The incidence of congenital malformation in bonafide congenital hypothyroidism is lower than has been previously reported. The high incidence of congenital malformation associated with transient TSH elevation indicates the need to reevaluate the diagnosis of hypothyroidism in all infants with TSH elevation and concurrent illness or malformation.

Case-Control Studies↗
PubMed1998

Human mesotheliomas contain the simian virus-40 regulatory region and large tumor antigen DNA sequences.

BACKGROUND: A cohort (20%) of patients with mesothelioma will not have an exposure to asbestos. Recently, a DNA tumor virus (simian virus 40) has been shown to cause hamster mesotheliomas; we previously described simian virus 40-like DNA amino terminus sequences in 29 of 48 mesotheliomas. We analyzed an additional 42 mesotheliomas to determine (1) whether our initial observations were durable and (2) the extent to which the simian virus 40 genome is present in mesotheliomas. METHODS: Genomic DNA was extracted from snap frozen mesothelioma tumor samples and from the simian virus 40-induced hamster mesothelioma tumor H9A. Polymerase chain reaction primers were used to amplify various simian virus 40 large T-antigen regions including a 105-base pair amino terminus fragment, a 281-base pair carboxyl terminus fragment, and a 310-base pair fragment of the enhancer promoter region. Endonuclease digestions and Southern blotting were used to verify the expected product. RESULTS: Thirty of the 42 (71%) samples amplified T-antigen amino sequences, and specificity was verified by Southern hybridization. Sixteen of 42 samples (38%) amplified the appropriate size fragment for the carboxyl terminus, and digestion with BsaB1 matched that of H9A. Twenty-two of 42 samples (52%) amplified simian virus 40 regulatory sequences and Fok1 digestion matched that of the hamster control tumor. Sequence analysis (4 patients) revealed 100% homology with the regulatory region of simian virus 40 strain 776. CONCLUSIONS: These data suggest an association between the simian virus 40 virus and human mesothelioma that could be exploited for diagnostic/therapeutic options including early detection and potential vaccination strategies.

Animals↗
PubMed1998

Maternal antibody to hepatitis B core antigen detected in dried neonatal blood spot samples.

Despite Department of Health recommendations, universal antenatal testing for hepatitis B virus (HBV) is not performed throughout Scotland. We describe the evaluation of an assay to document past or present infection with HBV, by identifying maternal antibody in routine Guthrie dried neonatal blood spot samples taken when infants are 7 days old. A modified haemagglutination assay to detect antibody to hepatitis B core antigen (CORECELL, Green Cross) was validated and found to be 79% sensitive (44/56) and 100% (105/105) specific when used with dried blood spot samples made from panels of serum of known reactivity. Ninety-three percent (13/14) of HBV carriers were CORECELL positive. Sixty-six (0.5%) of 14044 routine Guthrie samples taken from babies born in Scotland from June August 1992 were CORECELL positive indicating past or present maternal infection with HBV. A cross-sectional survey would document the maternity hospitals where universal antenatal hepatitis B screening should be urgently established.

Adult↗
PubMed1998

Hepatitis A vaccination of child care workers in Victoria: are recommendations being implemented?

This study examined the self-reported hepatitis A and B immunisation status of child care workers, the level of awareness among child care workers of the NHMRC recommendation for immunisation against hep. A and centre practices. A confidential mail survey was conducted in June 1996 with workers and co-ordinators from 113 randomly selected child care centres. Co-ordinators completed a questionnaire on the centre's characteristics and immunisation policy. Child care workers completed a second questionnaire on their immunisation knowledge or beliefs and immunisation status. Ninety-five centres (85%) and 607 (74%) workers participated. Only 11% of workers were vaccinated against hep. A, although the majority of child care worker respondents believed their occupation placed them at increased risk. Those vaccinated were more likely to be aware of the availability of hep. A vaccine, of the NHMRC recommendation for hep. A vaccination, and to have been vaccinated for hep. B. Centres in which co-ordinators perceived hep. A vaccination as important, and those which recorded staff immunisation, particularly hep. A, were more likely to have child care workers who were vaccinated against hep. A. In contrast, nearly two-thirds of child care workers reported that they were vaccinated against hep. B, although hep. B is not routinely recommended by the NHMRC for child care workers. These findings show a need for further policy and educational initiatives in the implementation of an immunisation strategy for child care workers.

Adult↗
PubMed1998

Aftereffects and sense of presence in virtual environments: formulation of a research and development agenda.

This report represents a committee summary of the current state of knowledge regarding aftereffects and sense of presence in virtual environments (VEs). The work presented in this article, and the proposed research agenda, are the result of a special session that was set up in the framework of the Seventh International Conference on Human Computer Interaction. Recommendations were made by the committee regarding research needs in aftereffects and sense of presence, and, where possible, priorities were suggested. The research needs were structured in terms of the short, medium, and long term and, if followed, should lead toward the effective use of VE technology. The 2 most critical research issues identified were (a) standardization and use of measurement approaches for aftereffects and (b) identification and prioritization of sensorimotor discordances that drive aftereffects. Identification of aftereffects countermeasures (i.e., techniques to assist users in readily transitioning between the real and virtual worlds), reduction of system response latencies, and improvements in tracking technology were also thought to be of critical importance.

Adaptation, Physiological↗
PubMed1998

Similarity comparisons with remembered and perceived magnitudes: memory psychophysics and fundamental measurement.

At the outset, subjects learned to associate a label with each element in a set of perceptual magnitudes (visual extents), using traditional paired-associate learning methods. Subsequently, on some trials, subjects indicated which pair of two pairs of labels corresponded to the more similar perceptual referents, and, on other trials, they selected the more dissimilar pair. It is shown that these similarity comparisons satisfy the axioms (transitivity and intradimensional subtractivity) necessary to conclude that they are based on computation of the difference of the differences of analogue-based interval scale representations. The findings also permitted refutation of the idea that memory for elementary percepts arises from their reperception. Notably, the memory exponent was 0.697, but the perception exponent was 0.546, and the reperception idea requires that the memory exponent be the square of the perception exponent (0.546(2) = 0.298). Symbolic distance effects and enhanced response time-based semantic congruity effects, typically found with binary comparisons, extend the range of commonalties found between perceptual and memory psychophysics.

Humans↗
PubMed1998

Mechanism of suppression of natural killer cell activity in trauma patients.

Trauma patients develop a severe immunosuppression that includes suppression of natural killer (NK) cell activity although numbers of NK cells are not reduced. The mechanism of suppression of NK cell activity after major trauma is not known. The aim of the present study was to investigate the in vitro effect of plasma samples from trauma patients (TP) on the cytotoxic activity of normal NK cells. Buffycoat mononuclear cells (5x10(5)/well) were preincubated with either TP or plasma samples from age and sex matched healthy controls (CP) for 0, 16 or 40 h. These effector cells were then cultured with 51Cr labeled K-562 cells (2x10(4)/well) for 4 h at 37 degrees C and % lysis was calculated. No significant differences in % lysis between CP and TP were found with 0 or 16 h preincubation, however 40 h preincubation with TP severely suppressed NK cell function (p=0.003) as compared to preincubation with CP for the same period. Addition of neutralizing anti-IL-4, anti-TGF-beta1, or anti-IL-10 antibodies did not reverse the NK cell suppression. There was a partial reversal of NK cell suppression by catalase but not by SOD or L-NMMA. Removal of monocytes from buffycoat mononuclear cells also significantly reversed the NK cell suppression. These data suggest that suppression of NK cell activity in trauma patients may be an accessory cell dependent phenomenon and may partially depend on production of reactive oxygen metabolites (ROM).

Catalase↗
PubMed1997

Enhanced expression of eotaxin and CCR3 mRNA and protein in atopic asthma. Association with airway hyperresponsiveness and predominant co-localization of eotaxin mRNA to bronchial epithelial and endothelial cells.

Eotaxin is a newly discovered C-C chemokine which preferentially attracts and activates eosinophil leukocytes by acting specifically on its receptor CCR3. The airway inflammation characteristic of asthma is believed to be, at least in part, the result of eosinophil-dependent tissue injury. This study was designed to determine whether there is increased expression of eotaxin and CCR3 in the bronchial mucosa of asthmatics and whether this is associated with disease severity. The major sources of eotaxin and CCR3 mRNA were determined by co-localization experiments. Bronchial mucosal biopsy samples were obtained from atopic asthmatics and normal non-atopic controls. Eotaxin and CCR3 mRNA were identified in tissue sections by in situ hybridization (ISH) using radiolabeled riboprobes and their protein product visualized by immunohistochemistry (IHC). Co-localization experiments were performed by double ISH/IHC. Eotaxin and CCR3 (mRNA and protein) were significantly elevated in atopic asthmatics compared with normal controls. In the asthmatics there was a highly significant inverse correlation between eotaxin mRNA+ cells and the histamine provocative concentration causing a 20% fall in FEV1 (PC20). Cytokeratin-positive epithelial cells and CD31+ endothelial cells were the major source of eotaxin mRNA whereas CCR3 co-localized predominantly to eosinophils. These data are consistent with the hypothesis that damage to the bronchial mucosa in asthma involves secretion of eotaxin by epithelial and endothelial cells resulting in eosinophil infiltration mediated via CCR3. Since selective (eotaxin) and non-selective C-C chemokines such as RANTES, MCP-3 and MCP-4 all stimulate eosinophils via CCR3, this receptor is potentially a prime therapeutic target in the spectrum of diseases involving eosinophil-mediated tissue damage.

Adult↗
PubMed1997

The validation of three human reliability quantification techniques--THERP, HEART and JHEDI: Part II--Results of validation exercise.

This is the second of three papers dealing with the validation of three Human Reliability Assessment (HRA) techniques. The first paper introduced the need for validation, the techniques themselves and pertinent validation issues. This second paper details the results of the validation study carried out on the Human Reliability Quantification techniques THERP, HEART and JHEDI. The validation study used 30 real Human Error Probabilities (HEPs) and 30 active Human Reliability Assessment (HRA) assessors, 10 per technique. The results were that 23 of the assessors showed a significant correlation between their estimates and the real HEPs, supporting the predictive accuracy of the techniques. Overall precision showed 72% (60-87%) of all HEPs to be within a factor of 10 of the true HEPs, with 38% of all estimates being within a factor of three of the true values. Techniques also tended to be pessimistic rather than optimistic, when they were imprecise. These results lend support to the empirical validity of these three approaches.

Benchmarking↗
PubMed1997

Prevention of postsurgical adhesions with N,O-carboxymethyl chitosan: examination of the most efficacious preparation and the effect of N,O-carboxymethyl chitosan on postsurgical healing.

BACKGROUND: Adhesion formation after operation can result in major complications. We have previously demonstrated that N,O-carboxymethyl chitosan (NOCC) is an effective inhibitor of postsurgical peritoneal adhesion formation. However, the optimal form of NOCC (i.e., cross-linked gel versus solution), as well as the best time of administration for optimal reduction in adhesion development, was not investigated. In addition, because adhesion formation and normal wound healing are related events and weakening of wound healing would be a serious drawback to the use of NOCC clinically, we wished to assess the effect of NOCC on the healing of surgical incisions. METHODS: Three surgical models were used: (1) an abdominal aortic anastomosis, (2) a large bowel anastomosis, and (3) an abdominal skin incision. In the first model Sprague-Dawley rats received an abdominal aortic transection and repair. NOCC solution or gel was administered at different time points throughout the procedure. Control and NOCC-treated animals were killed 14 days after operation. The condition of the anastomosed vessel was examined, and adhesion frequency and intensity in the abdomen were scored. In the second model Sprague-Dawley rats underwent large bowel transection and repair. Control and NOCC-treated animals were killed on postoperative days 4, 7, and 14, and strength of repair was assessed by removal of the large bowel and measurement of the bursting strength of the repaired incision. In the third model rats received an abdominal incision and were immediately closed. Control and NOCC-treated animals were killed 14 days after operation, and the skin tensile strength of the wound was measured with a tensiometer. RESULTS: In all three models studied, NOCC treatment did not adversely affect the strength of the repaired incision. NOCC solution administered before operation did not greatly reduce adhesion formation, whereas the delivery of both NOCC gel and solution after operation was most efficacious. CONCLUSIONS: The administration of both NOCC gel and solution after operation is most efficacious, and NOCC does not compromise postsurgical healing in rats at doses that prevent peritoneal adhesion formation.

Abdomen↗
PubMed1997

QC Validator 2.0: a computer program for automatic selection of statistical QC procedures for applications in healthcare laboratories.

A computer program has been developed to help healthcare laboratories select statistical control rules and numbers of control measurements that will assure the quality required by clinical decision interval criteria or analytical total error criteria. The program (QC Validator 2.0 (QC Validator and OPSpecs are registered trademarks of Westgard Quality Corporation, which has applied for a patent for this automatic QC selection process. Windows is a registered trademark of Microsoft Corporation)) runs on IBM compatible personal computers operating under Windows. The user enters information about the method imprecision, inaccuracy, and expected frequency of errors, defines the quality required in terms of a medically important change (clinical decision interval) or an analytical allowable total error, then initiates automatic selection by indicating the number of control materials that are to be analyzed (1, 2, or 3). The program returns with a chart of operating specifications (OPSpecs chart) that displays the selected control rules and numbers of control measurements. The automatic QC selection process is based on user editable criteria for the types of control rules that can be implemented by the laboratory, total numbers of control measurements that are practical, maximum levels of false rejections that can be tolerated and minimum levels of error detection that are acceptable for detection of medically important systematic or random errors.

Biometry↗
PubMed1997

Expression of an antigen homologous to the human CO17-1A/GA733 colon cancer antigen in animal tissues.

The CO17-1A/GA733 antigen is associated with human carcinomas and some normal epithelial tissues. This antigen has shown promise as a target in approaches to passive and active immunotherapy of colorectal cancer. The relevance of animal models for studies of immunotherapy targeting this antigen in patients is dependent on the expression of the antigen on normal animal tissues. Immunohistoperoxidase staining with polyclonal rabbit antibodies to the human antigen revealed the human homologue on normal small intestine, colon and liver of mice, rats and non-human primates, whereas mouse monoclonal antibodies to the CO17-1A or GA733 epitopes on the human antigen did not detect the antigen. Polyclonal rabbit antibodies, elicited by the murine antigen homologue derived from recombinant baculovirus-infected insect cells, immunoprecipitated the antigen from mouse small intestine, colon, stomach, kidney and lung. The isolated recombinant murine protein bound polyclonal, but not monoclonal, antibodies to the human CO17-1A/GA733 antigen, and recombinant human antigen bound polyclonal antibodies elicited by the murine antigen homologue. Thus, the antigen homologue expressed by animal tissues is similar, but not identical, to the human antigen. These results have important implications for experimental active and passive immunotherapy targeting the CO17-1A/GA733 antigen.

Animals↗