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Biomedical subjects

P A Marshall

Publications and source records attributed to P A Marshall.

At least 19 recordsLinked to original sources

Comparing bleaching and mortality responses of hard corals between southern Kenya and the Great Barrier Reef, Australia.

We compared the bleaching and mortality response (BMI) of 19 common scleractinian corals to an anomalous warm-water event in 1998 to determine the degree of variation between depths, sites, and regions. Mombasa corals experienced a greater temperature anomaly than those on the Great Barrier Reef (GBR) sites and this was reflected in the greater BMI response of most taxa. Comparing coral taxa in different sites at the same depth produced high correlation coefficients in the bleaching response in Kenya at 2 m (r=0.86) and GBR at 6 m depth sites (r=0.80) but less in the GBR for shallow 2 m sites (r=0.49). The pattern of taxa susceptibility was remarkably consistent between the regions. Coral taxa explained 52% of the variation in the response of colonies to bleaching between these two regions (Kenya BMI=0.90 GBR BMI+26; F(1,19) - 18.3; p < 0.001; r2 = 0.52). Stylophora and Pocillopora were consistently susceptible while Cyphastrea, Goniopora Galaxea and Pavona were resistant in both regions. Three taxa behaved differently between the two regions; Acropora, and branching Porites were both moderately affected on the GBR but were highly affected in Kenya while the opposite was true for Pavona. These results suggest that a colonies response to bleaching is phylogenetically constrained, emphasizing the importance of features of the host's physiology or morphology in determining the response to thermal stress.

Animals↗

Detection of high levels of congenital transmission of Toxoplasma gondii in natural urban populations of Mus domesticus.

The relative importance of different transmission routes of Toxoplasma gondii has been a matter for debate. This ubiquitous parasite is generally thought to be transmitted by infective oocysts excreted by the definitive host, the cat. Ingestion of undercooked meat has also been considered an important route of transmission in many mammals while congenital transmission has generally been considered relatively rare. Experimental studies demonstrate the ability of T. gondii to be transmitted congenitally, but few studies have investigated the frequency of this transmission route in natural populations. We use PCR amplification of the SAG1 gene to investigate the frequency of congenital transmission in a wild population of mice (Mus domesticus) and show that congenital transmission is occurring in 75% of pregnancies in this population. Furthermore, for infected pregnant mice, transmission occurs to at least one foetus in 100% of cases while variable penetrance of congenital infection is observed. These high levels of congenital transmission in this wild population of mice, taken together with other recent data on congenital transmission in sheep, suggests that this phenomenon might be more widespread than previously thought.

Animals↗

Ethical challenges in community-based research.

Investigators in population-based studies confront unique ethical challenges due to the community context of their research, their methods of inquiry, and the implications of their findings for social groups. Issues surrounding requirements for informed consent, the protection of privacy and confidentiality, and relationships between investigators and participants take on greater complexity and have significance beyond the individual research subject. In this paper, ethical challenges associated with community-based epidemiological research are briefly examined. We argue that ethically responsible population-based studies must seriously consider community needs and priorities and that researchers should work collaboratively with local populations to implement study goals. Strategies that promote respect for populations in community-based studies are outlined. These include community participation in research development, implementation and interpretation; adequate provision of information about study objectives to community members; and systematic feedback of study results.

Bioethical Issues↗

Ethical challenges in community-based research.

Investigators in population-based studies confront unique ethical challenges due to the community context of their research, their methods of inquiry, and the implications of their findings for social groups. Issues surrounding requirements for informed consent, the protection of privacy and confidentiality, and relationships between investigators and participants take on greater complexity and have significance beyond the individual research subject. In this paper, ethical challenges associated with community-based epidemiological research are briefly examined. We argue that ethically responsible population-based studies must seriously consider community needs and priorities and that researchers should work collaboratively with local populations to implement study goals. Strategies that promote respect for populations in community-based studies are outlined. These include community participation in research development, implementation and interpretation; adequate provision of information about study objectives to community members; and systematic feedback of study results.

Bioethical Issues↗

Teaching anthropology in the medical curriculum.

Practicing medicine well requires recognizing the breadth of human experience and attending to the psychological and sociocultural dimensions of patients as well as their physical needs. Central to the concerns of anthropology are the shared beliefs and values expressed in social practices and traditions that give meaning to everyday life. The relevance of anthropology for biomedical practice and research is grounded in the discipline's emphasis on contextual meaning and its unique strategies for data gathering. In this article, we briefly review the field of anthropology and the discipline of medical anthropology. We argue for incorporating anthropological concepts and methods in medical training, and summarize anthropology's role in medical education over the past century. Finally, we present ideas for including anthropology in the medical curriculum, proposing curricular goals and content, and teaching settings and techniques. An anthropological orientation can foster trainee self-awareness, help trainees prepare for the diverse perspectives they will encounter in our pluralistic society, and facilitate critical analysis of biomedicine and its systems of care.

Anthropology↗

Cultural and psychological dimensions of human organ transplantation.

Human organ transplantation is practiced in local cultural worlds that shape beliefs about appropriate conduct for its development and application. The psychological response of individuals to the transplant experience mediate and condition its life-changing force in the context of family and community. In this paper, three cases are examined to illustrate the impact of cultural and psychological influences on human organ replacement therapies. First, we explore brain death and its implications for the definition of death and the procurement of organs. A case example from Japan provides the framework for addressing the cultural foundations that contribute to perceptions of personhood and the treatment of the body. Second, we examine marketing incentives for organ donation using a case from India where, until recently, explicit forms of financial incentives have played a role in the development of renal transplantation involving non-related living donors. Third, we focus on the psychological remifications of organ transplantation using a case that demonstrates the profound experience of being the recipient of the "gift of life". Resolution of scientific and ethical challenges in the field of organ transplantation must consider the complex and significant impact of cultural and psychological factors on organ replacement therapies.

Attitude to Health↗

Marketing human organs: the autonomy paradox.

The severe shortage of organs for transplantation and the continual reluctance of the public to voluntarily donate has prompted consideration of alternative strategies for organ procurement. This paper explores the development of market approaches for procuring human organs for transplantation and considers the social and moral implications of organ donation as both a "gift of life" and a "commodity exchange." The problematic and paradoxical articulation of individual autonomy in relation to property rights and marketing human body parts is addressed. We argue that beliefs about proprietorship over human body parts and the capacity to provide consent for organ donation are culturally constructed. We contend that the political and economic framework of biomedicine, in western and non-western nations, influences access to transplantation technology and shapes the form and development of specific market approaches. Finally, we suggest that marketing approaches for organ procurement are and will be negotiated within cultural parameters constrained by several factors: beliefs about the physical body and personhood, religious traditions, economic conditions, and the availability of technological resources.

Altruism↗

Redox-sensitive homodimerization of Pex11p: a proposed mechanism to regulate peroxisomal division.

Pex11p (formerly Pmp27) has been implicated in peroxisomal proliferation (Erdmann, R., and G. Blobel. 1995. J. Cell Biol. 128; 509-523; Marshall, P.A., Y.I. Krimkevich, R.H. Lark, J.M. Dyer, M. Veenhuis, and J.M. Goodman, 1995. J. Cell Biol. 129; 345-355). In its absence, peroxisomes in Saccharomyces cerevisiae fail to proliferate in response to oleic acid; instead, one or two large peroxisomes are formed. Conversely, overproduction of Pex11p causes an increase in peroxisomal number. In this report, we confirm the function of Pex11p in organelle proliferation by demonstrating that this protein can cause fragmentation in vivo of large peroxisomes into smaller organelles. Pex11p is on the inner surface of the peroxisomal membrane. It can form homodimers, and this species is more abundant in mature peroxisomes than in proliferating organelles. Removing one of the three cysteines in the protein inhibits homodimerization. This cysteine 3-->alanine mutation leads to an increase in number and a decrease in peroxisomal density, compared with the wild-type protein, in response to oleic acid. We propose that the active species is the "monomeric" form, and that the increasing oxidative metabolism within maturing peroxisomes causes dimer formation and inhibition of further organelle division.

Base Sequence↗

Cross-cultural considerations in clinical ethics consultations.

Cross-cultural encounters between patients and physicians are now commonplace. Although increasing attention has been given to cultural issues in clinical medicine, there has been little discussion of cultural differences presenting as ethical dilemmas. We report four cases in which such differences led to requests for ethics consultations. In analyzing these cases, we identify four elements that are essential for successful resolution of such dilemmas: (1) an ability to communicate effectively with patients and their families; (2) a sufficient understanding of the patient's cultural background; (3) identification of culturally relevant value conflicts; and (4) a willingness to pursue discussion of the ethical dilemma until a compromise is reached or an otherwise satisfactory resolution of the problem is achieved. We conclude with several practical guidelines for clinicians facing ethical dilemmas in cross-cultural interactions with patients.

Adult↗

Medical students' first-person narratives of a patients story of AIDS.

Fourth year U.S. medical students' first-person narratives of a patient's experience of AIDS are analyzed using a conceptual framework that builds on the interactive model of narrative critique. Relational and affective convergence and, conversely, relational and affective dissonance, reveal imaginative reconstructions of emotional and interactional themes depicted in the patient's original story. Attention is focused on representations of isolation, contamination, shame and fear. Elements of indeterminacy and openness in the patient's description of his experience with AIDS provided students with opportunities to create an imagined response to HIV infection in their own narratives. The narratives describe social interaction that is tainted and constrained by the presence of infection and its associated stigma. The emotional content of the student narratives portrays an affective landscape that resonates. elaborates and, in some cases, distorts the feelings expressed in the patient's story. The narratives call attention to the way in which individual meanings are externalized, objectified and projected onto a socially and morally salient 'other'. Using the first-person narrative approach in the seminar on AIDS proved to be an effective method of sensitizing students to the experience of living with HIV infection. The challenge for medical educators lies in creating opportunities for students to develop increased empathy toward individuals with AIDS.

Acquired Immunodeficiency Syndrome↗

Pmp27 promotes peroxisomal proliferation.

Peroxisomes perform many essential functions in eukaryotic cells. The weight of evidence indicates that these organelles divide by budding from preexisting peroxisomes. This process is not understood at the molecular level. Peroxisomal proliferation can be induced in Saccharomyces cerevisiae by oleate. This growth substrate is metabolized by peroxisomal enzymes. We have identified a protein, Pmp27, that promotes peroxisomal proliferation. This protein, previously termed Pmp24, was purified from peroxisomal membranes, and the corresponding gene, PMP27, was isolated and sequenced. Pmp27 shares sequence similarity with the Pmp30 family in Candida boidinii. Pmp27 is a hydrophobic peroxisomal membrane protein but it can be extracted by high pH, suggesting that it does not fully span the bilayer. Its expression is regulated by oleate. The function of Pmp27 was probed by observing the phenotype of strains in which the protein was eliminated by gene disruption or overproduced by expression from a multicopy plasmid. The strain containing the disruption (3B) was able to grow on all carbon sources tested, including oleate, although growth on oleate, glycerol, and acetate was slower than wild type. Strain 3B contained peroxisomes with all of the enzymes of beta-oxidation. However, in addition to the presence of a few modestly sized peroxisomes seen in a typical thin section of a cell growing on oleate-containing medium, cells of strain 3B also contained one or two very large peroxisomes. In contrast, cells in a strain in which Pmp27 was overexpressed contained an increased number of normal-sized peroxisomes. We suggest that Pmp27 promotes peroxisomal proliferation by participating in peroxisomal elongation or fission.

Acetates↗

The Candida boidinii peroxisomal membrane protein Pmp30 has a role in peroxisomal proliferation and is functionally homologous to Pmp27 from Saccharomyces cerevisiae.

The mechanism of peroxisome proliferation is poorly understood. Candida boidinii is a methylotrophic yeast that undergoes rapid and massive peroxisome proliferation and serves as a good model system for this process. Pmp30A and Pmp30B (formerly designated Pmp31 and Pmp32, respectively) are two closely related proteins in a polyploid strain of this yeast that are strongly induced by diverse peroxisome proliferators such as methanol, oleate, and D-alanine. The function of these proteins is not understood. To study this issue, we used a recently described haploid strain (S2) of C. boidinii that can be manipulated genetically. We now report that strain S2 contains a single PMP30 gene very similar in sequence (greater than 93% identity at the DNA level) to PMP30A and PMP30B. When PMP30 was disrupted, cell growth on methanol was greatly inhibited, and cells grown in both methanol and oleate had fewer, larger, and more spherical peroxisomes than wild-type cells. A similar phenotype was recently described for Saccharomyces cerevisiae cultured on oleate in which PMP27, which encodes a protein of related sequence that is important for peroxisome proliferation, was disrupted. To determine whether Pmp27 is a functional homolog of Pmp30, gentle complementation was performed. PMP30A was expressed in the PMP27 disruptant of S. cerevisiae, and PMP27 was expressed in the PMP30 disruptant of C. boidinii S2. Complementation, in terms of both cell growth and organelle size, shape, and number, was successful in both directions, although reversion to a wild-type phenotype was only partial for the PMP30 disruptant. We conclude that these proteins are functional homologs and that both Pmp30 and Pmp27 have a direct role in proliferation and organelle size rather than a role in a specific peroxisomal metabolic pathway of substrate utilization.

Amino Acid Sequence↗

Pharmacy computer prescription databases: methodologic issues of access and confidentiality.

OBJECTIVE: To examine methodologic issues of access and confidentiality regarding the use of pharmacy computer prescription databases (PCPDs) for participant selection to receive mailed, self-administered, hypertensive quality-of-life survey outside a primary-care setting. DESIGN: Two separate PCPD searches by pharmacist owners for patients prescribed at least one of 130 potential antihypertensive medications. The first PCPD used a nonrandom sample of all patients (n = 635); the second PCPD used a random sample (n = 100) of three specific antihypertensive drug groups. Research protocol was approved by the investigators' institutional review board. SETTING: Two independent, privately owned PCPDs. PATIENTS OR OTHER PARTICIPANTS: Individuals prescribed at least 1 of 130 PCPD medications potentially used in antihypertensive treatment. INTERVENTIONS: Individually addressed cover letter on pharmacy letterhead signed by a pharmacist requesting voluntary completion of the enclosed, self-administered, opinion survey on quality of life. MAIN OUTCOME MEASURE: Anonymous survey return to off-site post office box in envelope provided. RESULTS: Favorable or no opposition to PCPD methodology from pharmacist or participants. Ethical opposition was encountered when incorporating PCPD sampling technique into grant proposal. CONCLUSIONS: The American Pharmaceutical Association Code of Ethics is used as a basis to provide recommendations to examine and justify PCPD investigative use. Increasing availability of PCPD technology encourages more efficient and easier methods of research strategy. PCPD use, however, demands identical stringent guidelines used in traditional research and raises potential issues regarding pharmacist-patient confidentiality as well as the right of PCPD use by others.

Clinical Pharmacy Information Systems↗