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P Cowan

Publications and source records attributed to P Cowan.

At least 19 recordsLinked to original sources
PubMed2005

Prevention of hyperacute rejection in a model of orthotopic liver xenotransplantation from pig to baboon using polytransgenic pig livers (CD55, CD59, and H-transferase).

INTRODUCTION: The search for alternative sources for transplant organs leads us to the search for animals as an inexhaustible source of organs. The objective of this study was to analyze whether livers from polytransgenic pigs expressing the human complement regulatory proteins CD55 (hDAF), CD59, and alfa alpha1,2-fucosyltransferase (H-transferase), protected against hyperacute rejection after orthotopic liver xenotransplantation to a baboon and also to study pig liver function in a nonhuman primate. MATERIALS AND METHODS: Nine liver transplants from pig to baboon were divided into two groups: a control group (n = 4) of genetically unmodified pigs and an experimental group (n = 5) of pigs transgenic for CD55, CD59, and H-transferase as donors. All the donating piglets obtained through hysterectomy were maintained in specific pathogen-free conditions. The selection of transgenic pig donors followed demonstration of transgene expression using monoclonal antibodies (antiCD55, antiCD59) and immunohistological studies on liver biopsies. RESULTS: All animals in the control group developed hyperacute rejection with survival rates less than 16 hours without function of transplanted livers. In the experimental group none of the animals suffered hyperacute rejection. Survival in this group was between 13 and 24 hours. The livers were functional, producing bile and maintaining above 35% prothrombin activity. Only in one case was there primary dysfunction of the xenograft. CONCLUSION: Polytransgenic livers for complement regulatory proteins prevent hyperacute rejection when xenotransplanted into a baboon.

Acute Disease↗
PubMed2005

The launch of MCBEND 10.

MCBEND 10 is the latest release of the general radiation transport Monte Carlo code from the ANSWERS Software Service of Serco Assurance. MCBEND is developed within a Nuclear Code Development (NCD) partnership between Serco Assurance and BNFL. The ANSWERS vision is 'to provide easy-to-use software that meets the current and emerging needs of the user community'. In the case of MCBEND, this vision focuses on the key areas of accuracy, understanding of uncertainties, efficiency and user-friendliness. MCBEND 10 is a major launch of the code with many new and enhanced features. New developments in MCBEND 10 include automatic splitting mesh generation, point energy adjoint for neutrons, calculation of uncertainty in the results due to material cross section uncertainties and a unified source facility. Enhanced features include improved temperature treatment, extended scoring of sensitivity to geometry perturbations, geometry improvements, extensions to formulae and improved user guide image. The user-friendliness of the MCBEND code has been further enhanced by recent developments to the visualisation tools, VISAGE and VISTA-RAY. Developments have been made to the three-dimensional visualisation tool, VISTA-RAY, to simplify the detailed checking of a model, with the option to use a mouse-pointer to select regions of interest for further detail and to visually highlight incorrectly defined areas. A further development to VISTA-RAY is the inclusion of the capability to overlay a representation of a user-designated set of results from a MCBEND analysis on the model. Improvements have also been made to the graphical user interface LaunchPad for submitting and controlling calculation submission, with a common user-image across all the systems. Recent enhancements to LaunchPad include a job-scheduler to simplify processing multiple tasks. A selection of the new developments in MCBEND 10, VISTA-RAY and LaunchPad will be described in this paper.

Algorithms↗
PubMed2003

Mortality rate and movements of brushtail possums with clinical tuberculosis (Mycobacterium bovis) infection.

AIM: To describe the mortality rate and movements of brushtail possums (Trichosurus vulpecula) with clinical tuberculosis (Mycobacterium bovis) from a site in native podocarp/hardwood forest, in the Orongorongo Valley, Wellington. METHODS: Possums with clinical tuberculosis (Tb) were identified through routine trapping on live capture grids and were fitted with radio-collars, and located at approximately monthly intervals for 2.5 years. The survival times of radio-collared tuberculous and non-diseased possums were used to estimate the instantaneous additional mortality rate due to clinical Tb. The spatial behaviour of clinically tuberculous possums was compared with that of non-diseased possums, using both den and trap locations. The frequency of long-distance movements of both tuberculous and non-diseased possums was also determined. A possum was defined as having undertaken along-distance movement when it moved at least 200 m from the centre of its activity range and then returned to its established activity range or died. RESULTS: The mean survival time of clinically tuberculous possums was 4.7 (SE 0.79) months. The instantaneous additional mortality rate due to clinical Tb was estimated to be between 1.08 year-1 and 2.38 year-1, with the lower figure including an unknown portion of the incubation period in the estimate. Estimates of denning and activity ranges of tuberculous possums were approximately 22-30% larger, on average, than the ranges of non-diseased possums, but the differences were not significant. Both tuberculous and non-diseased possums undertook long-distance movements up to 700 m from the centre of their activity range. However, the majority of tuberculous possums died within or near their established activity range. CONCLUSIONS: This study estimated the mortality rate during the clinical stages of Tb and, as such, did not represent a true estimate of the disease-induced mortality rate (alpha) used in most epidemiological models of possums and Tb. However, the lower estimate of the additional mortality rate due to clinical disease could be considered an approximation to alpha. The movement patterns of clinically tuberculous possums were, overall, not substantially different from non-diseased possums. The occurrence of long-distance movements by tuberculous possums sometimes coincided with the advanced stage of clinical disease. However, the majority of tuberculous possums died within their established activity area. Long-distance movements by resident possums during the terminal stages of disease represent a direct risk for transmission of Tb to livestock on farms within approximately 1 km of infected possum populations.

Journal Article↗
PubMed2000

Naturally acquired anti-alpha Gal antibodies in a murine allograft model similar to delayed xenograft rejection.

Antibodies directed against galactose-alpha1,3-galactose (alphaGal) are believed to play an important role in the pathogenesis of delayed xenograft rejection (DXR). This study was designed to determine whether alpha1,3-galactosyltransferase-deficient (Gal KO) mice can naturally acquire a sufficient anti-alphaGal titre to cause the delayed type rejection of alphaGal-expressing hearts. Gal KO mice of various ages were assessed for anti-alphaGal antibody levels. alphaGal-expressing hearts were transplanted heterotopically into these mice and monitored daily. Rejecting and surviving hearts were evaluated histologically. In Gal KO mice greater than 6-month-old, 64% had an anti-alphaGal antibody titre above the background level. When wild-type alphaGal-expressing hearts were transplanted into this group, 45% of grafts rejected within 5 to 13 days. Histological examination of the rejected hearts displayed marked tissue damage and an inflammatory infiltrate of predominantly macrophage/monocytes. Surviving grafts showed preserved morphology. Like humans, Gal KO mice naturally develop anti-alphaGal antibodies with age. The titre in these mice was sufficient to cause a "delayed-type" rejection of a significant proportion of alphaGal-expressing cardiac grafts. This model thus provides an opportunity to investigate the role of naturally acquired anti-alphaGal antibodies in the pathogenesis of DXR.

Animals↗
PubMed2000

Eighteen years of experience with adult and pediatric liver transplantation at the University of Tennessee, Memphis.

1. Since its inception, the liver program at UT Memphis has been striving to serve its population by stressing access, technical innovation, and by its focus on quality of life. The results for both adult and pediatric transplants over the past 18 years demonstrate that small and medium-sized programs can function efficiently and are valuable for their local communities. 2. Patient and graft survival rates exceeded 85% in the pediatric population in the first year with the 5-, 10-, and 15-year results above 75%. 3. Patient and graft survival rates in adults were 83% at one year, 68% at 5 years, and 60% at 10 years. 4. Innovative techniques in liver transplantation have had a dramatic impact on accessibility of pediatric recipients to liver transplantation and recently are becoming crucial for select populations of adults requiring expedited transplantation.

Adult↗
PubMed1999

Protection against hyperacute xenograft rejection of transgenic rat hearts expressing human decay accelerating factor (DAF) transplanted into primates.

BACKGROUND: Production of transgenic pigs for multiple transgenes is part of a potential strategy to prevent immunological events involved in xenograft rejection. Use of a genetically engineerable rodent as a donor in primates could allow testing in vivo of the effects of different transgenes on controlling xenograft rejection. As a first step in the development of a donor containing multiple transgenes, transgenic rats for human decay-accelerating factor (DAF) were used as heart donors to test their resistance against complement (C)-mediated rejection by non-human primates. MATERIALS AND METHODS: Transgenic rats were generated by using a construct containing the human DAF cDNA under the transcriptional control of the endothelial cell (EC)-specific human ICAM-2 promoter. DAF expression was evaluated by immunohistology and by FACS analysis of purified ECs. Resistance of transgenic hearts against C-mediated damage was evaluated by ex vivo perfusion with human serum and by transplantation into cynomolgus monkeys. RESULTS: Immunohistological analysis of DAF expression in several organs from two transgenic lines showed uniform expression on the endothelium of all blood vessels. ECs purified from transgenic hearts showed 50% DAF expression compared to human ECs and >70% reduction of C-dependent cell lysis compared to control rat ECs. Hemizygous transgenic hearts perfused with human serum showed normal function for >60 min vs. 11. 2 +/- 1.7 min in controls. Hemi- or homozygous transgenic hearts transplanted into cynomolgus monkeys showed longer survival (15.2 +/- 7 min and >4.5 hr, respectively) than controls (5.5 +/- 1.4 min). In contrast to hyperacutely rejected control hearts, rejected homozygous DAF hearts showed signs of acute vascular rejection (AVR) characterized by edema, hemorrhage, and an intense PMN infiltration. CONCLUSIONS: We demonstrate that endothelial-specific DAF expression increased heart transplant survival in a rat-to-primate model of xenotransplantation. This will aid in the analysis of AVR and of new genes that may inhibit this form of rejection, thus helping to define strategies for the production of transgenic pigs.

Animals↗
PubMed1997

Genetically variable triplet repeats in a RING-finger ORF of Helicoverpa species baculoviruses.

Nucleotide sequence analysis of the Helicoverpa zea S-type nucleopolyhedrovirus (HzSNPV) genomic interval between the polh and iel genes has revealed an open reading frame (HOAR ORF) that contains a complex A 1-T rich triplet repeat region (RAT-repeats). HOAR ORF is predicted to encode an acidic, arginine residue rich. 712 aa protein, with a C3HC4 (RING-finger) zinc binding motif. RAT-repeats, distributed over 450 bp. consist of GAT. AAT, and GTT codons, correspond to Asp, Asn and Val residues which display an extreme codon bias not seen with nine other genes of this virus. A survey of four other (field) isolates of Helicoverpa sp. NPVs confirms a high incidence of mutation in the RAT-repeat region. A 158-bp conserved block, homologous to the pe38-ien promoter of AcMNPV, was identified upstream of HOAR ORF. The sub-region of the genome in which HOAR ORF is located is susceptible to rearrangement.

Amino Acid Sequence↗
PubMed1997

A randomized trial of group outpatient visits for chronically ill older HMO members: the Cooperative Health Care Clinic.

OBJECTIVE: To compare the impact of group outpatient visits to traditional "physician-patient dyad" care among older chronically ill HMO members on health services utilization and cost, self-reported health status, and patient and physician satisfaction. DESIGN: A 1-year randomized trial. SETTING: A group model HMO in the Denver Metropolitan area. PARTICIPANTS: Three hundred twenty-one members aged 65 and older, randomized to a group visit intervention (n = 160) or to usual care (n = 161). INTERVENTION: Patients with high health services utilization and one or more chronic conditions had monthly group visits with their primary care physician and nurse. Visits included health education, prevention measures, opportunities for socialization, mutual support, and for one-to-one consultations with their physician, where necessary. MEASUREMENTS: Health services utilization and associated cost, health status, and patient and physician satisfaction. RESULTS: Outcome measures obtained after a 1-year follow-up period showed that group participants had fewer emergency room visits (P = .009), visits to subspecialists (P = .028), and repeat hospital admissions per patient (P = .051). Group participants made more visits (P = .021) and calls (P = .038) to nurses than control group patients and fewer calls to physicians (P = .019). In addition, a greater percentage of group participants received influenza and pneumonia vaccinations (P < .001). Group participants had greater overall satisfaction with care (P = .019), and participating physicians reported higher levels of satisfaction with the groups than with individual care. No differences were observed between groups on self-reported health and functional status. Cost of care per member per month was $14.79 less for the group participants. CONCLUSIONS: Group visits for chronically ill patients reduce repeat hospital admissions and emergency care use, reduce cost of care, deliver certain preventive services more effectively, and increase patient and physician satisfaction.

Aged↗
PubMed1995

Who's got the power? Gender differences in partners' perceptions of influence during marital problem-solving discussions.

Previous research on marital communication indicates that women have more influence in marital problem solving because they raise the issues and shape the discussion. Other studies suggest that men have the power in marital problem solving. This study re-examines power and influence from the partners' point of view. Twenty-seven couples-18 with a first child under 2, and 9 undecided about having children-were videotaped while working on a self-selected problem concerning their division of family labor. Data sources included: (a) transcribed audiotaped accounts given by each partner while viewing a videotape of their problem-solving discussion; (b) self-report questionnaires; and (c) ratings by a research team of the concordance between spouses' accounts. Husbands and wives were perceived as having a primary influence on different aspects of the discussion. Women tended to raise the issues and draw men out in the early phase of the discussion, while men controlled the content and emotional depth of the later discussion phases, and largely determined the outcome. The women's accounts emphasized that their influence in the early phase was often illusory: their behavior was shaped primarily by the effort to choose strategies that would avoid upsetting their husbands. In terms of overall satisfaction with marriage, wives had greater tolerance than their husbands for conflict in the area of division of domestic labor, but less tolerance for their husbands' domination of the discussion process. Women's marital satisfaction was higher when there was concordance between spouses in their accounts of their problem-solving discussion. This research highlights the importance of eliciting spouses' own perceptions and definitions in understanding the impact of gender-linked power differences in martial communication.

Adult↗
PubMed1994

Development of exclusivity in perceptually based categories of young infants.

The exclusivity of perceptually defined categorical representations for natural animal categories in young infants was investigated. Previously, as well as in Experiment 1, evidence was obtained for a categorical representation for cats in 3- and 4-month-old infants that excluded dogs but included perceptually similar female lions after a number of different familiarization procedures. However, in Experiment 2 both dogs and female lions were found to be excluded when the initial familiarization with cats alone was followed by six pairings of familiar cats and novel lions intermingled with two added pairings of familiar cats. The present results indicate that a categorical representation can attain a high level of exclusivity during early infancy as a consequence of experience with exemplars of the contrasting categories that accents the perceptual similarities among members of a category and the perceptual differences among exemplars from different categories.

Animals↗
PubMed1994

Nucleotide sequence of the polyhedrin gene region of Helicoverpa zea single nucleocapsid nuclear polyhedrosis virus: placement of the virus in lepidopteran nuclear polyhedrosis virus group II.

The polyhedrin gene (polh) of Helicoverpa zea single nucleocapsid nuclear polyhedrosis virus (HzSNPV) was identified and shown by sequence analysis of the EcoRI I genomic fragment to encode a 246 amino acid polypeptide that has greater than 80% sequence identity to known polyhedrins. It is preceded by an AT-rich region containing the conserved late promoter motif TAAG, which was identified as a transcription start point. Downstream of polh there were several similarities in genome arrangement to other nuclear polyhedrosis viruses (NPVs). These include open reading frame (ORF) 8, immediately downstream of polh, encoding a 412 amino acid protein with multiple tandem proline residues, which is homologous to ORF8 (ORF1629) of Autographa californica multiple nucleocapsid NPV. Phylogenetic analysis of the polh gene region shows that HzSNPV is a member of the previously described lepidopteran NPV group II and that it is most closely related to polh of the NPVs of Malacosoma nuestria, Spodoptera littoralis, Orgyia pseudotsugata (single nucleocapsid-type virus) and Buzura supressaria.

Amino Acid Sequence↗
PubMed1993

Renal responses to nifedipine and captopril in hypertensive insulin-dependent diabetic men: a randomized cross-over study.

The effects of nifedipine retard and captopril on renal haemodynamic parameters have been examined in a double blind randomised cross-over trial in 10 insulin-dependent diabetic males with hypertension (systolic pressure > 150 mmHg or diastolic pressure > 90 mmHg). The acute renal haemodynamic response to nifedipine retard 20 mg and captopril 25 mg was monitored at the start of therapy and again after 8 weeks treatment with nifedipine retard 20 mg b.d. and captopril 25 mg b.d. Blood pressure fell from 148/97 +/- 4/2 (SEM) during the run-in phase to 135/87 +/- 4/1.5 on nifedipine retard and to 131/83 +/- 5/1 on captopril. There was no difference between the initial renal response to the two agents; an increase in renal plasma flow and a non-significant decline in glomerular filtration rate resulted in similar decreases in filtration fraction. After 8 weeks therapy, neither drug had a significant effect on urinary albumin excretion. Baseline renal function did not differ and no acute changes in renal haemodynamics were seen after nifedipine. Following captopril there was no acute change in systemic blood pressure but RPF rose from 572 +/- 41 to 638 +/- 42 ml/min per 1.73 m2 (P < 0.05) and filtration fraction fell from 0.21 to 0.16 (P < 0.02). This sustained acute response of the renal circulation to angiotensin-converting enzyme (ACE) inhibition after chronic therapy may be relevant to the apparent renal protection afforded by ACE inhibitors in experimental nephropathies.

Adult↗
PubMed1993

Going home: easing the transition for the mentally ill.

Health care in the 90s dictates an increased pressure to discharge patients from the hospital into the community, placing much of the burden of care on families. With budget constraints in effect and bed shortages and closures a reality, the health care system is keenly aware of the need to prevent illness relapse and to promote safe functioning in the community, especially for people who suffer from persistent mental health problems.

Caregivers↗