Article

Personality Changes Following Heart Transplantation: The Role of Cellular Memory

Article

Personality Changes Following Heart Transplantation: The Role of Cellular Memory

If you want to read the PDF, try requesting it from the authors.

Abstract

Personality changes following heart transplantation, which have been reported for decades, include accounts of recipients acquiring the personality characteristics of their donor. Four categories of personality changes are discussed in this article: (1) changes in preferences, (2) alterations in emotions/temperament, (3) modifications of identity, and (4) memories from the donor's life. The acquisition of donor personality characteristics by recipients following heart transplantation is hypothesized to occur via the transfer of cellular memory, and four types of cellular memory are presented: (1) epigenetic memory, (2) DNA memory, (3) RNA memory, and (4) protein memory. Other possibilities, such as the transfer of memory via intracardiac neurological memory and energetic memory, are discussed as well. Implications for the future of heart transplantation are explored including the importance of reexamining our current definition of death, studying how the transfer of memories might affect the integration of a donated heart, determining whether memories can be transferred via the transplantation of other organs, and investigating which types of information can be transferred via heart transplantation. Further research is recommended.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the author.

... Such changes have been categorized as: a. changes in preferences b. alterations in emotions/temperament, c. modifications of identity d. memories from the donor's life [ 28] According to the observations of Dr. Paul Pearsall, the heart transplant recipients seem to be the most susceptible to significant changes in personality. He has published the accounts of seventy-three patients. ...
... The theory of cellular memories states that memories, as well as personality traits, are not only stored in the brain but may also be stored in organs such as the heart. Cellular memory has been suggested to explain the transfer of personal memories from donor to recipient following heart transplantation [28,29]. The various types of cellular memory include Epigenetic memory, RNA memory and Protein memory. ...
... The other types of memory which, in addition, could contribute to the transfer of memories, from donor to recipient are: Cardiac neurological memory: It is known that the heart has two distinct networks of nerves, one consisting of nerve cells within the heart (intracardiac nervous system), and the other made up of nerves originating outside the heart. Whereas both the networks have the potential to encode, store, and retrieve memories, only the nerves within the intracardiac nervous system are transplanted with the heart [28]. The intracardiac nervous system remodels itself after cardiac transplantation, a process known as neuroplasticity. ...
Article
Full-text available
Human heart, "a wondrous magic casket", has been believed to be the seat of intelligence, emotion and sensation in ancient scriptures and non-Abrahamic religions. According to monotheistic religions, it has psychological, moral and spiritual functions. It could either be healthy or diseased. The modern scientific research has proved that an emotional brain is formed long before a rational one, and the heart has its own independent complex nervous system known as 'the brain in the heart.' The heart sends out electromagnetic field which controls our emotions. Whereas the theory of cellular memories states that memories, as well as personality traits, are not only stored in the brain but may also be stored in organs such as the heart, it has been reported that the heart transplant recipients seem to be the most susceptible to significant changes in personality, the possible mechanism being the transfer of memory through heart. The heart also manufactures and secretes oxytocin, referred as "love or social-bonding hormone". Moreover, its role in cognition, tolerance, trust and friendship and the establishment of enduring pair-bonds has been well recognized.
... Although it is considered that personality traits overall are stable across time, people's personality might change under the influence of different environmental and contextual factors such as stressful life events or highly impressive experiences (Liester, 2020;Wagner et al., 2020). Therefore, it fits the logic that certain types of travel experiences might influence tourists' personality traits. ...
... Personality traits are usually stable in different situations across time (Mottus et al., 2017). However, recent research shows that personality might change under the influence of environmental and contextual factors such as significant life events or transformative travel experiences (Bleidorn et al., 2018;Liester, 2020;Wagner et al., 2020). ...
Article
Tourist transformation has recently received ample attention. Although personality traits are considered to be overall stable across time, there is evidence that personality might change under the influence of different environmental and contextual factors such as those offered in transformative travel experiences. This study developed and validated a scale to measure travelers’ personality changes after transformative travel experiences. The steps of the study include personality change scale item generation, scale purification, and construct validation with principal component analysis and confirmatory factor analysis. The study results indicated the validity of a six-dimensional tourist transformation scale that may be effective in capturing travelers’ personality change through travel experiences. Keywords: transformation, transformative experience, tourism, personality traits, self-change
... In searching for the basis of the memory explanation we are up to date coming to the same fundamental problems: How are the memories formed, stored, how long can they last, and how are they recalled/retrieved? Moreover, an increasing number of data (Bunzel et al. 1992;Pearsall et al. 2000;Liester 2020;Tan et al. 2020) suggests that memories can be stored in the heart and recalled/retrieved from this organ. ...
... Exosomes are a subset of EVs, with an average diameter of approximately 30-150 nanometers (for review see Kalluri & LeBleu 2020). Exosomes as the vehicles of RNA memory transfer have been described earlier (Liester 2020), however, among dozens of other possibilities. ...
Article
Full-text available
Here we present a hypothetical explanation of the donor "heart memory transfer" in patients after heart transplantation. The donor heart can accumulate the memory engrams which are formed in the brain of the donor and hypothetically retransfers it to the brain of the recipient in the form of exosomes. The support comes from data obtained from a small albeit statistically not disregarded group of patients.
... However, if we invoke the notion of the "spirit of the gift," we may envisage that the recipient may experience along with the delivery of a gift a particular nature or spirit of the donor that creates a bond between the donor and the recipient. We may also note Mauss's postulation that the "spirit of the gift possessed an inner force that was invested with life and carried the individuality of the donor" [21,22]. ...
... In this sense, the article explains the "absence of investigation" that exists to comprehend "such personality changes and the scepticism regarding whether such changes are possible" [22]. ...
Article
Full-text available
This article aims to describe the relationship between donors and their recipients in the context of organ transplants. This analysis is made in the light of Marcel Mauss’s work, offering an expansion on an analysis of his discussion on the “spirit of the gift” and his idea that gifts require reciprocation. It is argued that some recipients of donated organs receive a personal element from the donor in that there is a transfer or sharing of the donors’ personality and spiritual qualities. The article examines the nature of this form of “interconnectedness”. The article considers the qualities of this form of interconnectedness between donors and recipients by examining two specific cases of gift giving. One such case concerns the accounts of the reception of organs by recipients and how they may feel connected with a donated entity. The second case of gifting is the case of Tibetan lamas concerning their funeral ceremonies, where, following cremation, their relics are donated to disciples. This “donation” does not take place by dissecting useable parts of a body for use in another person, but rather by ingestion of the remains of the corpse following cremation. This example shows how such “donations” are seen as incorporating the spiritual qualities and attributes of the donor [1]. The article concludes that while scholars have employed different forms of metaphors to understand the cultural context of organ donations this article analyzes the elements of the “spirit of the gift.” This form of analysis may best be understood in terms of Mauss’s notions of the return of the gift and the creation of a “communal bond”.
... Hafızanın intrakardiyak nörolojik hafıza ve enerjik hafıza yoluyla transferi gibi diğer olasılıklar da tartışılmaktadır. Mevcut ölüm tanımımızı yeniden gözden geçirmenin önemi, anıların transferinin bağışlanan bir kalbin entegrasyonunu nasıl etkileyebileceğinin araştırılması, anıların diğer organların transplantasyonu yoluyla aktarılıp aktarılamayacağının belirlenmesi ve araştırılması dahil olmak üzere kalp transplantasyonunun ilginç bir çalışma yapılmıştır(53). ...
Chapter
Full-text available
KOKSOY H. (2022). Hücrelerimiz Bizi Duyar mı? Epigenetik, Nöroplastisite ve Genetik Determinizm. Insac World Health Sciences. Eds, Assoc. Prof. Dr. Mehmet DALKILIC and Asst. Prof. Dr. Hale KOKSOY, 1nd ed., pp. 760-774 , Gece Kitaplığı Press. June 2022. ISBN: 978-625-430-152-0.
... Moreover, non-neuronal information processing was reported in skeletal muscle, heart, and fascia, indicating that neuronal cells do not hold the exclusive monopoly on cognitive processes [133,134]. Along this line, the acquisition of donor personality characteristics following heart transplantation, documented by numerous studies, may reflect EC-mediated cognition [135][136][137]. This is in line with the hemo-neural hypothesis that connects information processing to endothelial blood flow [138]. ...
Article
Full-text available
Infection with SARS-CoV-2, the causative agent of the COVID-19 pandemic, originated in China and quickly spread across the globe. Despite tremendous economic and healthcare devastation, research on this virus has contributed to a better understanding of numerous molecular pathways, including those involving γ-aminobutyric acid (GABA), that will positively impact medical science, including neuropsychiatry, in the post-pandemic era. SARS-CoV-2 primarily enters the host cells through the renin–angiotensin system’s component named angiotensin-converting enzyme-2 (ACE-2). Among its many functions, this protein upregulates GABA, protecting not only the central nervous system but also the endothelia, the pancreas, and the gut microbiota. SARS-CoV-2 binding to ACE-2 usurps the neuronal and non-neuronal GABAergic systems, contributing to the high comorbidity of neuropsychiatric illness with gut dysbiosis and endothelial and metabolic dysfunctions. In this perspective article, we take a closer look at the pathology emerging from the viral hijacking of non-neuronal GABA and summarize potential interventions for restoring these systems.
... Interestingly, human tissues, such as the skeletal muscle, fascia and blood cells may process and store information, further implicating microtubules and tubulin in cognition (Moore and Cao, 2008;Tozzi, 2014;Snijders et al., 2020). In this regard, acquisition of donor personality traits, was documented after cardiac transplants, suggesting that information processing and storing may be a decentralized, blockchain phenomenon (Liester, 2020). Indeed, earlier studies have linked cognition to tubulin and tubulin inhibiting chemotherapy with dysfunctional memory (Craddock et al., 2012;Tuszynski et al., 2020;Kalra et al., 2020). ...
Article
Full-text available
A growing body of epidemiological and research data has associated neurotropic viruses with accelerated brain aging and increased risk of neurodegenerative disorders. Many viruses replicate optimally in senescent cells, as they offer a hospitable microenvironment with persistently elevated cytosolic calcium, abundant intracellular iron, and low interferon type I. As cell-cell fusion is a major driver of cellular senescence, many viruses have developed the ability to promote this phenotype by forming syncytia. Cell-cell fusion is associated with immunosuppression mediated by phosphatidylserine externalization that enable viruses to evade host defenses. In hosts, virus-induced immune dysfunction and premature cellular senescence may predispose to neurodegenerative disorders. This concept is supported by novel studies that found postinfectious cognitive dysfunction in several viral illnesses, including human immunodeficiency virus-1, herpes simplex virus-1, and SARS-CoV-2. Virus-induced pathological syncytia may provide a unified framework for conceptualizing neuronal cell cycle reentry, aneuploidy, somatic mosaicism, viral spreading of pathological Tau and elimination of viable synapses and neurons by neurotoxic astrocytes and microglia. In this narrative review, we take a closer look at cell-cell fusion and vesicular merger in the pathogenesis of neurodegenerative disorders. We present a “decentralized” information processing model that conceptualizes neurodegeneration as a systemic illness, triggered by cytoskeletal pathology. We also discuss strategies for reversing cell-cell fusion, including, TMEM16F inhibitors, calcium channel blockers, senolytics, and tubulin stabilizing agents. Finally, going beyond neurodegeneration, we examine the potential benefit of harnessing fusion as a therapeutic strategy in regenerative medicine.
... [6] Some scientists believe that a new heart may cause important physical and mental changes, but these changes are not that extensive to cause deep changes in personality. [7,8] Almgren et al. stated that due to dependence and problems before transplantation, health level and QOL of people improve after transplantation, and changes in peoples' attitude and lifestyle are consistent with their new life conditions. [9] The results of studies are different in this regard. ...
Background: Although the phenomenon of adjustment to a new heart in transplant recipients is very complex, very few studies have been conducted on this important issue. Therefore, no careful and clear definition exists for this concept. Materials and methods: This concept analysis was conducted in Iran in 2018 on 13 patients undergoing heart transplantation. In the theoretical phase, a conceptual framework was created according to the existing data in the literature about the phenomenon. In this study, 13 participants were selected using purposive sampling with maximum diversity.-Ž In the fieldwork phase, 20 deep and semistructured interviews were conducted with patients undergoing heart transplantation over 4 months. After data saturation, interviews were analyzed using the qualitative content analysis method proposed by Granheim and Lundman (2009). At the final analytical phase, the results of the two previous phases were integrated using a hybrid model. Results: Adjustment to a new heart is a unique multiphase process in patients undergoing heart transplantation. The antecedents include the transplantation time, physical conditions, social and family support, relationship with congeners, and spiritual beliefs. The desirable consequences of adjustment to a new heart may include a new life, inner peace, and spiritual excellence, and the undesirable consequences may include psychological abuse and emotional stagnation. Conclusions: According to the results, the health-care team should consider the patient as a unique client and initiate discussions before and following heart transplantation that address patients' adjustment to a new heart in all their physical, sexual, and emotional aspects.
... Sheldrake convincingly argues that in addition to the brain, the rest of the body is involved in the work of the mind. For example, there are documented cases in which organ transplants transferred memories and character traits of transplant donors to recipients (Joshi, 2011;Liester, 2020;Pearsall et al., 2002;Sheldrake, 2009) . This is in agreement with our model that unites the DNA of all the cells of the brain and the rest of the body into a single oscillator. ...
Preprint
Full-text available
This paper continues the series of papers on DNA resonance signaling. Previously the authors proposed that DNA is involved in the work of mind directly and immediately via the network of optical fibers. The authors proposed the mechanism of signal transduction in DNA via a sequence-specific resonance between the clouds of delocalized charges in the base stack. It was computationally demonstrated that certain repetitive patterns of delocalized charge clouds were evolutionarily enriched in various genomes. Here, the authors propose that natural quantum computation in DNA in living cells is based on the tautomerization of basepairs and involves coordinated oscillations of hydrogen-bond protons and aromatic electrons. The authors expand the ORCH-OR theory to include the collapse of the wave function of aromatic electrons in purines and propose that such collapses and expansions produce the experience of consciousness and the perception of time. The above mechanisms are supported by an observation that the majority of the psychoactive drugs are aromatic and the suggestion that they modify the aromaticity of DNA by binding to it. Quantum mechanical considerations for the collapse of aromaticity by double proton transfer in basepairs are discussed in terms of the collapse of the wave function, loss of delocalization, and the dynamic balance between coherence and decoherence in DNA.
Book
Full-text available
INSAC WORLD HEALTH SCIENCES
Chapter
Full-text available
This paper continues the series of papers on DNA resonance signaling. The authors previously proposed that DNA is involved in the work of the mind directly and immediately via the network of optical fibers. The authors proposed the mechanism of signal transduction in DNA via a sequence-specific resonance between the clouds of delocalized charges in the base stack. It was computationally demonstrated that certain repetitive patterns of delocalized charge clouds were evolutionarily enriched in various genomes. Here, the authors propose that natural quantum computation in DNA in living cells is based on the tautomerization of basepairs and involves coordinated oscillations of hydrogen-bond protons and aromatic electrons. The authors expand the ORCH-OR theory to include the collapse of the wave function of aromatic electrons in purines and propose that such collapses and expansions produce the experience of consciousness and the perception of time. The above mechanisms are supported by an observation that the majority of the psychoactive drugs are aromatic and the suggestion that they modify the aromaticity of DNA by binding to it. Quantum mechanical considerations for the collapse of aromaticity by double proton transfer in basepairs are discussed in terms of the collapse of the wave function, loss of delocalization, and the dynamic balance between coherence and decoherence in DNA.
Article
Full-text available
The precise nature of the engram, the physical substrate of memory, remains uncertain. Here, it is reported that RNA extracted from the central nervous system of Aplysia given long-term sensitization (LTS) training induced sensitization when injected into untrained animals; furthermore, the RNA-induced sensitization, like training-induced sensitization, required DNA methylation. In cellular experiments, treatment with RNA extracted from trained animals was found to increase excitability in sensory neurons, but not in motor neurons, dissociated from naïve animals. Thus, the behavioral, and a subset of the cellular, modifications characteristic of a form of nonassociative long-term memory (LTM) in Aplysia can be transferred by RNA. These results indicate that RNA is sufficient to generate an engram for LTS in Aplysia and are consistent with the hypothesis that RNA-induced epigenetic changes underlie memory storage in Aplysia.
Article
Full-text available
Exosomes are involved in the progression of neurodegenerative diseases. The cellular prion protein (PrPC) is highly expressed on exosomes. In neurodegenerative diseases, PrPC has at least two functions: It is the substrate for the generation of pathological prion protein (PrPSc), a key player in the pathophysiology of prion diseases. On the other hand, it binds neurotoxic amyloid-beta (Aß) oligomers, which are associated with initiation and progression of Alzheimer's disease (AD). This has direct consequences for the role of exosomal expressed PrPC. In prion diseases, exosomal PrP leads to efficient dissemination of pathological prion protein, thus promoting spreading and transmission of the disease. In AD, exosomal PrPC can bind and detoxify Aß oligomers thus acting protective. In both scenarios, assessment of the state of PrPC on exosomes derived from blood or cerebrospinal fluid (CSF) may be useful for diagnostic workup of these diseases. This review sums up current knowledge of the role of exosomal PrPC on different aspects of Alzheimer's and prion disease.
Article
Full-text available
Most, if not all, cells of the cardiovascular system secrete small, lipid bilayer vesicles called exosomes. Despite technical challenges in their purification and analysis, exosomes from various sources have been shown to be powerfully cardioprotective. Indeed, it is possible that much of the so-called "paracrine" benefit in cardiovascular function obtained by stem cell therapy can be replicated by the injection of exosomes produced by stem cells. However, exosomes purified from plasma appear to be just as capable of activating cardioprotective pathways. We discuss the potential roles of endogenous exosomes in the cardiovascular system, how this is perturbed in cardiovascular disease, and evaluate their potential as therapeutic agents to protect the heart.
Article
Full-text available
Epigenetic programming and reprogramming are at the heart of cellular differentiation and represent developmental and evolutionary mechanisms both in germ-line and somatic cell lines. Only about 2% of our genome is composed of protein-coding genes, while the remaining 98%, once considered "junk" DNA, codes for regulatory/epigenetic) elements that control how genes are expressed in different tissues and across time from conception to death. While we already know that epigenetic mechanisms are at play in cancer development and in regulating metabolism (cellular and whole body), the role of epigenetics in the developing prenatal and postnatal brain, and in maintaining a proper brain activity throughout the various stages of life, in addition to having played a critical role in human evolution, is a relatively new domain of knowledge. Here we present the current state-of-the-art techniques and results of these studies within the domain of emotions, and then speculate how genomic and epigenetic mechanisms can modify and potentially alter our emotional, limbic, brain and affect our social interactions. This article is protected by copyright. All rights reserved.
Article
Full-text available
The mechanism of memory remains one of the great unsolved problems of biology. Grappling with the question more than a hundred years ago, the German zoologist Richard Semon formulated the concept of the engram, lasting connections in the brain that result from simultaneous "excitations", whose precise physical nature and consequences were out of reach of the biology of his day. Neuroscientists now have the knowledge and tools to tackle this question, however, and this Forum brings together leading contemporary views on the mechanisms of memory and what the engram means today.
Article
Full-text available
Our memories are the records of the experiences we gain in our everyday life. Over time, they slowly transform from an initially unstable state into a long-lasting form. Many studies have been investigating from different aspects how a memory could persist for sometimes up to decades. In this review, we highlight three of the greatly addressed mechanisms that play a central role for a given memory to endure: the allocation of the memory to a given neuronal population and what brain areas are recruited for its storage; the structural changes that underlie memory persistence; and finally the epigenetic control of gene expression that might regulate and support memory perseverance. Examining such key properties of a memory is essential towards a finer understanding of its capacity to last.
Article
Full-text available
This paper will focus on electromagnetic fields generated by the heart that permeate every cell and may act as a synchronizing signal for the body in a manner analogous to information carried by radio waves. Particular emphasis will be devoted to evidence demonstrating that this energy is not only transmitted internally to the brain but is also detectable by others within its range of communication. Finally, data will be discussed indicating that cells studied in vitro are also responsive to the heart’s bioelectromagnetic field.
Article
Full-text available
Of heart transplant recipients, 30 per cent report ongoing or episodic emotional issues post-transplant, which are not attributable to medications or pathophysiological changes. To this end, our team theorized that cardiac transplantation introduces pressing new questions about how patients incorporate a transplanted heart into their sense of self and how this impacts their identity. The work of Merleau-Ponty provided the theoretical underpinning for this project as it rationalizes how corporeal changes affect one's self and offer an innovative framework to access these complex aspects of living with a transplanted heart. We used visual methodology and recorded 25 semi-structured interviews videographically. Both visual and verbal data were analyzed at the same time in an iterative process. The most common theme was that participants expressed a disruption to their own identity and bodily integrity. Additionally, participants reported interconnectedness with the donor, even when the transplanted heart was perceived as an intruder or stranger. Finally, transplant recipients were very vivid in their descriptions and speculation of how they imagined the donor. Receiving an anonymous donor organ from a stranger often leaves the recipient with questions about who they themselves are now. Our study provides a nuanced understanding of heart transplant recipients' embodied experiences of self and identity. Insights gained are valuable to educate transplant professionals to develop new supportive interventions both pre- and post-transplant, and to improve the process of informed consent. Ultimately, such insights could be used to enable heart transplant recipients to incorporate the graft optimally over time, easing distress and improving recovery. © The Author(s) 2014.
Article
Full-text available
Exosomes are tiny vesicles (30-150 nm) constantly secreted by all healthy and abnormal cells, and found in abundance in all body fluids. These vesicles, loaded with unique RNA and protein cargo, have a wide range of biological functions, including cell-to-cell communication and signalling. As such, exosomes hold tremendous potential as biomarkers and could lead to the development of minimally invasive diagnostics and next generation therapies within the next few years. Here, we describe the strategies for isolation of exosomes from human blood serum and urine, characterization of their RNA cargo by sequencing, and present the initial data on exosome labelling and uptake tracing in a cell culture model. The value of exosomes for clinical applications is discussed with an emphasis on their potential for diagnosing and treating neurodegenerative diseases and brain cancer.
Article
Full-text available
Although genetics has an essential role in defining the development, morphology, and physiology of an organism, epigenetic mechanisms have an essential role in modulating these properties by regulating gene expression. During development, epigenetic mechanisms establish stable gene expression patterns to ensure proper differentiation. Such mechanisms also allow organisms to adapt to environmental changes and previous experiences can impact the future responsiveness of an organism to a stimulus over long timescales and even over generations. Here, we discuss the concept of epigenetic memory, defined as the stable propagation of a change in gene expression or potential induced by developmental or environmental stimuli. We highlight three distinct paradigms of epigenetic memory that operate on different timescales.
Article
Full-text available
How epigenetic information is transmitted from generation to generation remains largely unknown. Deletion of the C. elegans histone H3 lysine 4 dimethyl (H3K4me2) demethylase spr-5 leads to inherited accumulation of the euchromatic H3K4me2 mark and progressive decline in fertility. Here, we identified multiple chromatin-modifying factors, including H3K4me1/me2 and H3K9me3 methyltransferases, an H3K9me3 demethylase, and an H3K9me reader, which either suppress or accelerate the progressive transgenerational phenotypes of spr-5 mutant worms. Our findings uncover a network of chromatin regulators that control the transgenerational flow of epigenetic information and suggest that the balance between euchromatic H3K4 and heterochromatic H3K9 methylation regulates transgenerational effects on fertility.
Article
Full-text available
Exosomes are small vesicles (50–150 nm) of endocytic origin that are released by many different cell types. Exosomes in the tumor microenvironment may play a key role in facilitating cell-cell communication. Exosomes are reported to predominantly contain RNA and proteins. In this study, we investigated whether exosomes from pancreatic cancer cells and serum from patients with pancreatic ductal adenocarcinoma contain genomic DNA. Our results provide evidence that exosomes contain >10-kb fragments of double-stranded genomic DNA. Mutations in KRAS and p53 can be detected using genomic DNA from exosomes derived from pancreatic cancer cell lines and serum from patients with pancreatic cancer. In addition, using whole genome sequencing, we demonstrate that serum exosomes from patients with pancreatic cancer contain genomic DNA spanning all chromosomes. These results indicate that serum-derived exosomes can be used to determine genomic DNA mutations for cancer prediction, treatment, and therapy resistance.
Article
Full-text available
Background Exosomes, endosome-derived membrane microvesicles, contain specific RNA transcripts that are thought to be involved in cell-cell communication. These RNA transcripts have great potential as disease biomarkers. To characterize exosomal RNA profiles systemically, we performed RNA sequencing analysis using three human plasma samples and evaluated the efficacies of small RNA library preparation protocols from three manufacturers. In all we evaluated 14 libraries (7 replicates). Results From the 14 size-selected sequencing libraries, we obtained a total of 101.8 million raw single-end reads, an average of about 7.27 million reads per library. Sequence analysis showed that there was a diverse collection of the exosomal RNA species among which microRNAs (miRNAs) were the most abundant, making up over 42.32% of all raw reads and 76.20% of all mappable reads. At the current read depth, 593 miRNAs were detectable. The five most common miRNAs (miR-99a-5p, miR-128, miR-124-3p, miR-22-3p, and miR-99b-5p) collectively accounted for 48.99% of all mappable miRNA sequences. MiRNA target gene enrichment analysis suggested that the highly abundant miRNAs may play an important role in biological functions such as protein phosphorylation, RNA splicing, chromosomal abnormality, and angiogenesis. From the unknown RNA sequences, we predicted 185 potential miRNA candidates. Furthermore, we detected significant fractions of other RNA species including ribosomal RNA (9.16% of all mappable counts), long non-coding RNA (3.36%), piwi-interacting RNA (1.31%), transfer RNA (1.24%), small nuclear RNA (0.18%), and small nucleolar RNA (0.01%); fragments of coding sequence (1.36%), 5′ untranslated region (0.21%), and 3′ untranslated region (0.54%) were also present. In addition to the RNA composition of the libraries, we found that the three tested commercial kits generated a sufficient number of DNA fragments for sequencing but each had significant bias toward capturing specific RNAs. Conclusions This study demonstrated that a wide variety of RNA species are embedded in the circulating vesicles. To our knowledge, this is the first report that applied deep sequencing to discover and characterize profiles of plasma-derived exosomal RNAs. Further characterization of these extracellular RNAs in diverse human populations will provide reference profiles and open new doors for the development of blood-based biomarkers for human diseases.
Article
Full-text available
Extracellular vesicles (EVs) carry signals within or at their limiting membranes, providing a mechanism by which cells can exchange more complex information than what was previously thought. In addition to mRNAs and microRNAs, there are DNA fragments in EVs. Solexa sequencing indicated the presence of at least 16434 genomic DNA (gDNA) fragments in the EVs from human plasma. Immunofluorescence study showed direct evidence that acridine orange-stained EV DNAs could be transferred into the cells and localize to and inside the nuclear membrane. However, whether the transferred EV DNAs are functional or not is not clear. We found that EV gDNAs could be homologously or heterologously transferred from donor cells to recipient cells, and increase gDNA-coding mRNA, protein expression, and function (e.g. AT1 receptor). An endogenous promoter of the AT1 receptor, NF-κB, could be recruited to the transferred DNAs in the nucleus, and increase the transcription of AT1 receptor in the recipient cells. Moreover, the transferred EV gDNAs have pathophysiological significance. BCR/ABL hybrid gene, involved in the pathogenesis of chronic myeloid leukemia, could be transferred from K562 EVs to HEK293 cells or neutrophils. Our present study shows that the gDNAs transferred from EVs to cells have physiological significance, not only to increase the gDNA-coding mRNA and protein levels, but also to influence function in recipient cells.
Article
Full-text available
Digital production, transmission and storage have revolutionized how we access and use information but have also made archiving an increasingly complex task that requires active, continuing maintenance of digital media. This challenge has focused some interest on DNA as an attractive target for information storage because of its capacity for high-density information encoding, longevity under easily achieved conditions and proven track record as an information bearer. Previous DNA-based information storage approaches have encoded only trivial amounts of information or were not amenable to scaling-up, and used no robust error-correction and lacked examination of their cost-efficiency for large-scale information archival. Here we describe a scalable method that can reliably store more information than has been handled before. We encoded computer files totalling 739 kilobytes of hard-disk storage and with an estimated Shannon information of 5.2 × 10(6) bits into a DNA code, synthesized this DNA, sequenced it and reconstructed the original files with 100% accuracy. Theoretical analysis indicates that our DNA-based storage scheme could be scaled far beyond current global information volumes and offers a realistic technology for large-scale, long-term and infrequently accessed digital archiving. In fact, current trends in technological advances are reducing DNA synthesis costs at a pace that should make our scheme cost-effective for sub-50-year archiving within a decade.
Article
Full-text available
Shedding microvesicles are membrane released vesicles derived directly from the plasma membrane. Exosomes are released membrane vesicles of late endosomal origin that share structural and biochemical characteristics with prostasomes. Microvesicles/exosomes can mediate messages between cells and affect various cell-related processes in their target cells. We describe newly detected microvesicles/exosomes from cardiomyocytes and depict some of their biological functions. Microvesicles/exosomes from media of cultured cardiomyocytes derived from adult mouse heart were isolated by differential centrifugation including preparative ultracentrifugation and identified by transmission electron microscopy and flow cytometry. They were surrounded by a bilayered membrane and flow cytometry revealed presence of both caveolin-3 and flotillin-1 while clathrin and annexin-2 were not detected. Microvesicle/exosome mRNA was identified and out of 1520 detected mRNA, 423 could be directly connected in a biological network. Furthermore, by a specific technique involving TDT polymerase, 343 different chromosomal DNA sequences were identified in the microvesicles/exosomes. Microvesicle/exosomal DNA transfer was possible into target fibroblasts, where exosomes stained for DNA were seen in the fibroblast cytosol and even in the nuclei. The gene expression was affected in fibroblasts transfected by microvesicles/exosomes and among 333 gene expression changes there were 175 upregulations and 158 downregulations compared with controls. Our study suggests that microvesicles/exosomes released from cardiomyocytes, where we propose that exosomes derived from cardiomyocytes could be denoted "cardiosomes", can be involved in a metabolic course of events in target cells by facilitating an array of metabolism-related processes including gene expression changes.
Article
Full-text available
The existence of circulating microRNAs (miRNAs) in the blood of cancer patients has raised the possibility that miRNAs may serve as a novel diagnostic marker. However, the secretory mechanism and biological function of extracellular miRNAs remain unclear. Here, we show that miRNAs are released through a ceramide-dependent secretory machinery and that the secretory miRNAs are transferable and functional in the recipient cells. Ceramide, whose biosynthesis is regulated by neutral sphingomyelinase 2 (nSMase2), triggers secretion of small membrane vesicles called exosomes. The decreased activity of nSMase2 with a chemical inhibitor, GW4869, and a specific small interfering RNA resulted in the reduced secretion of miRNAs. Complementarily, overexpression of nSMase2 increased extracellular amounts of miRNAs. We also revealed that the endosomal sorting complex required for transport system is unnecessary for the release of miRNAs. Furthermore, a tumor-suppressive miRNA secreted via this pathway was transported between cells and exerted gene silencing in the recipient cells, thereby leading to cell growth inhibition. Our findings shed a ray of light on the physiological relevance of secretory miRNAs.
Article
Cardiac transplantation is a viable therapeutic alternative for patients with end‐stage heart disease, which offers a favourable short‐ and medium‐term prognosis. The survival has improved from 20% of patients who survived at one year after transplantation in the 1960s to the present figures of 80%‐85% of patients who are alive at one year, and 50%‐70% of patients who are alive at five years, after transplantation. Therefore, it seems timely to focus attention on the psychological well‐being of cardiac‐ transplant recipients. The medical literature is scant in regard to the psychiatric and the psychosocial impact of cardiac transplantation on recipients, and a systematic and prospective study of the psychosocial adaptation of recipients is lacking. Since 1984, we have been studying the emotional impact of cardiac transplantation on recipients and their families. This article presents the results for a group of recipients who have been assessed before transplantation, then followed‐up at discharge from hospital and at four, eight and 12 months after transplantation. The study attempted to quantitate the recipients' anxiety, depression, body image and subjective quality of life by way of standardized self‐assessment questionnaires. The recipients' satisfaction with relationships or their marital situation also was reported, as were their degree of rehabilitation at 12 months and their attitudes to various aspects of treatment after the transplantation. Before the transplantation, 53% of patients reported an increase in anxiety and 34% of patients recorded scores that indicated mild‐to‐moderate levels of depression. Thirty‐seven per cent of patients showed a deterioration in the quality of their lives and 34% of patients had a negative body image. After the transplantation, significant improvements occurred in all parameters, which were maintained at follow‐up.
Article
Exosomes have become an important player in intercellular signaling. These lipid microvesicles can stably transfer miRNA, protein, and other molecules between cells and circulate throughout the body. Exosomes are released by almost all cell types and are present in most if not all biological fluids. The biologically active cargo carried by exosomes can alter the phenotype of recipient cells. Exosomes increasingly are recognized as having an important role in the progression and treatment of cardiac disease states. Injured cardiac cells can release exosomes with important pathological effects on surrounding tissue, in addition to effecting other organs. But of equal interest is the possible benefit(s) conferred by exosomes released from stem cells for use in treatment and possible repair of cardiac damage.
Article
Cardiac function is under the control of the autonomic nervous system, composed by the parasympathetic and sympathetic divisions, which are finely tuned at different hierarchical levels. While a complex regulation occurs in the central nervous system involving the insular cortex, the amygdala and the hypothalamus, a local cardiac regulation also takes place within the heart, driven by an intracardiac nervous system. This complex system consists of a network of ganglionic plexuses and interconnecting ganglions and axons. Each ganglionic plexus contains numerous intracardiac ganglia that operate as local integration centres, modulating the intricate autonomic interactions between the extrinsic and intracardiac nervous systems. Herein, we summarize the current understanding on the intracardiac nervous system, and acknowledge its role in the pathophysiology of cardiovascular diseases.
Article
Prions are proteins that can adopt self-perpetuating conformations and are traditionally regarded as etiological agents of infectious neurodegenerative diseases in humans, such as Creutzfeldt-Jakob disease, kuru, and transmissible encephalopathies. More recently, a growing consensus has emerged that prion-like, self-templating mechanisms also underlie a variety of neurodegenerative disorders, including amyotrophic lateral sclerosis, Alzheimer's disease, and Huntington's disease. Perhaps most surprising, not all prion-like aggregates are associated with pathological changes. There are now several examples of prion-like proteins in mammals that serve positive biological functions in their aggregated state. In this review, we discuss functional prions in the nervous system, with particular emphasis on the cytoplasmic polyadenylation element-binding protein (CPEB) and the role of its prion-like aggregates in synaptic plasticity and memory. We also mention a more recent example of a functional prion-like protein in the brain, TIA-1, and its role during stress. These studies of functional prion-like proteins have provided a number of generalizable insights on how prion-based protein switches may operate to serve physiological functions in higher eukaryotes.
Article
It is becoming increasingly clear that small vesicles released from cells (extracellular vesicles [EVs]) represent a heterogeneous population implicated in cell-to-cell communication. The classifications and nomenclature of EVs are evolving as enrichment strategies and specific characteristics are being unraveled. At present, physical properties of EVs-namely, size, shape, and density-are often used to identify subpopulations of EVs. A distinct group of EVs, termed exosomes, largely defined by their small size (∼40-150 nm) and proposed subcellular origin, has been extensively studied in several aspects of cancer biology. Exosomes are implicated in modulating behavior of cancer cells as well as the immune and angiogenic responses in tumors, possibly contributing to cancer progression locally and systemically. Most intriguingly, the nucleic acid content of exosomes has been proposed to play a role in oncogenic transformation and transfer of cancer-specific genome to promote cancer pathogenesis. Here, we specifically focus on the discovery of exosomal DNA, studies related to the origin of genomic DNA in exosomes, and its utility in cancer diagnosis and disease monitoring.
Article
In the embryonic and adult brain, neural stem cells proliferate and give rise to neurons and glia through highly regulated processes. Epigenetic mechanisms - including DNA and histone modifications, as well as regulation by non-coding RNAs - have pivotal roles in different stages of neurogenesis. Aberrant epigenetic regulation also contributes to the pathogenesis of various brain disorders. Here, we review recent advances in our understanding of epigenetic regulation in neurogenesis and its dysregulation in brain disorders, including discussion of newly identified DNA cytosine modifications. We also briefly cover the emerging field of epitranscriptomics, which involves modifications of mRNAs and long non-coding RNAs.
Article
Prions are a self-templating amyloidogenic state of normal cellular proteins, such as prion protein (PrP). They have been identified as the pathogenic agents, contributing to a number of diseases of the nervous system. However, the discovery that the neuronal RNA-binding protein, cytoplasmic polyadenylation element-binding protein (CPEB), has a prion-like state that is involved in the stabilization of memory raised the possibility that prion-like proteins can serve normal physiological functions in the nervous system. Here, we review recent experimental evidence of prion-like properties of neuronal CPEB in various organisms and propose a model of how the prion-like state may stabilize memory. © 2016 Cold Spring Harbor Laboratory Press; All rights reserved.
Article
Consolidation of implicit memory in the invertebrate Aplysia and explicit memory in the mammalian hippocampus are associated with remodeling and growth of preexisting synapses and the formation of new synapses. Here, we compare and contrast structural components of the synaptic plasticity that underlies these two distinct forms of memory. In both cases, the structural changes involve time-dependent processes. Thus, some modifications are transient and may contribute to early formative stages of long-term memory, whereas others are more stable, longer lasting, and likely to confer persistence to memory storage. In addition, we explore the possibility that trans-synaptic signaling mechanisms governing de novo synapse formation during development can be reused in the adult for the purposes of structural synaptic plasticity and memory storage. Finally, we discuss how these mechanisms set in motion structural rearrangements that prepare a synapse to strengthen the same memory and, perhaps, to allow it to take part in other memories as a basis for understanding how their anatomical representation results in the enhanced expression and storage of memories in the brain. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.
Article
Consolidation of long-term memories depends on de novo protein synthesis. Several translational regulators have been identified, and their contribution to the formation of memory has been assessed in the mouse hippocampus. None of them, however, has been implicated in the persistence of memory. Although persistence is a key feature of long-term memory, how this occurs, despite the rapid turnover of its molecular substrates, is poorly understood. Here we find that both memory storage and its underlying synaptic plasticity are mediated by the increase in level and in the aggregation of the prion-like translational regulator CPEB3 (cytoplasmic polyadenylation element-binding protein). Genetic ablation of CPEB3 impairs the maintenance of both hippocampal long-term potentiation and hippocampus-dependent spatial memory. We propose a model whereby persistence of long-term memory results from the assembly of CPEB3 into aggregates. These aggregates serve as functional prions and regulate local protein synthesis necessary for the maintenance of long-term memory. Copyright © 2015 Elsevier Inc. All rights reserved.
Article
-Whether biomechanical force on the heart can induce exosome secretion to modulate cardiovascular function is not known. We investigated the secretion and activity of exosomes containing a key receptor in cardiovascular function, the Angiotensin II Type I Receptor (AT1R). -Exosomes containing AT1Rs were isolated from the media overlying AT1R-overexpressing cells exposed to osmotic stretch and from sera of mice undergoing cardiac pressure overload. The presence of AT1Rs in exosomes was confirmed by both electron microscopy and radioligand receptor binding assays, and shown to require β-arrestin2, a multifunctional adaptor protein essential for receptor trafficking. We show that functional AT1Rs are transferred via exosomes in an in vitro model of cellular stretch. Using mice with global and cardiomyocyte conditional deletion of β-arrestin2, we show that under conditions of in vivo pressure overload the cellular source for the exocytosis of exosomes containing AT1R is the cardiomyocyte. Exogenous administered AT1R-enriched exosomes target cardiomyocytes, skeletal myocytes and mesenteric resistance vessels, and is sufficient to confer blood pressure responsiveness to angiotensin II infusion in AT1R knockout mice. -This work reveals that AT1R-enriched exosomes are released from the heart under conditions of in vivo cellular stress to likely modulate vascular responses to neurohormonal stimulation. In the context of the whole organism, the concept of G protein-coupled receptor trafficking should consider circulating exosomes as part of the reservoir of functional AT1Rs.
Article
Research efforts during the past decades have provided intriguing evidence suggesting that stressful experiences during pregnancy exert long-term consequences on the future mental wellbeing of both the mother and her baby. Recent human epidemiological and animal studies indicate that stressful experiences in utero or during early life may increase the risk of neurological and psychiatric disorders, arguably via altered epigenetic regulation. Epigenetic mechanisms, such as miRNA expression, DNA methylation, and histone modifications are prone to changes in response to stressful experiences and hostile environmental factors. Altered epigenetic regulation may potentially influence fetal endocrine programming and brain development across several generations. Only recently, however, more attention has been paid to possible transgenerational effects of stress. In this review we discuss the evidence of transgenerational epigenetic inheritance of stress exposure in human studies and animal models. We highlight the complex interplay between prenatal stress exposure, associated changes in miRNA expression and DNA methylation in placenta and brain and possible links to greater risks of schizophrenia, attention deficit hyperactivity disorder, autism, anxiety - or depression-related disorders later in life. Based on existing evidence, we propose that prenatal stress, through the generation of epigenetic alterations, becomes one of the most powerful influences on mental health in later life. The consideration of ancestral and prenatal stress effects on lifetime health trajectories is critical for improving strategies that support healthy development and successful aging.
Article
Discusses the nature of the synthetic unity of consciousness. The phenomena is also known as 'knowing of things together'. There are 2 ways of knowing things - knowing them immediately or intuitively, and knowing them conceptually or representatively. To know an object, is to lead to it through a context which the world supplies. To know immediately or intuitively, implies that the mental content and object are identical. The general nature of being-known together can never be accounted for, as it seems to be the ultimate essence of all experience. Several factors are responsible for the union in consciousness: Attention, reminiscence, synergy, relating to self, relating to other objects, the individual soul, and the world-soul. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Chapter
Immunological memory is a distinct characteristic of the immune system and it relates to its ability to remember antigens on pathogens, tumour cells, tissue of the immunological self, and cells and tissues derived from other individuals of the species and mount an immunological response of greater magnitude and with faster kinetics upon re-encounter of the same antigens. This property provides an advantage in the course of protective responses against pathogens and tumour cells, but represents a threat in the case of allogeneic cell or tissue transplant. During the past decade considerable progress has been made in the elucidation of the multiple cellular and molecular mechanisms regulating the induction and maintenance of immunological memory. Although our understanding remains imperfect, the current cumulative information allows one to recognise operational patterns and identify those principles that will aid in the design of better vaccines and better understanding the role of immune system in protection against disease.
Article
Transplantation represents in the popular mind the pinnacle of biomedical knowledge and skill. Its feasibility depends upon the management of conflicting cultural values surrounding death and dying, where diverse parties consider bodies and their parts to be personal property, sacred entities, or offerings to the common good. Specifically within the specialized transplant community, viable organs are scarce, socially valuable resources. The ideology that guides transplant professionals, however, is rife with contradictions: close inspection reveals unease over definitions of death and rights to body parts. Ideological disjunction arises from the competing needs to personalize and to objectify organs and bodies. Organ recipients struggle with these contradictory messages as they rebuild their sense of self and self-worth following transplantation. This transformative process is explored by analyzing professional writings and data generated from ethnographic research in the United States. The study ends by examining transformed identity as fictionalized and extended biography.
Article
Background: Whether cardiac reinnervation occurs after transplantation remains controversial. If reinnervation does occur, how sympathetic and parasympathetic efferent neurons do this remains unknown. Methods: Power spectral analysis of heart rate variability was assessed for 1 year after cardiac autotransplantation in 9 dogs. After induction of anesthesia 13 months after transplantation, cardiac and intrinsic cardiac neuronal responses elicited by both electrical stimulation of parasympathetic or sympathetic efferent neurons and systemic or local coronary artery administration of nicotine (5 microg/kg), angiotensin II (0.75 microg/kg), and tyramine (1.2 microg/kg) were studied. The transmembrane electrical properties of intrinsic cardiac neurons were studied in vitro. Ventricular tissue catecholamine content, alpha-tubulin expression, and beta-adrenergic receptor density and affinity were studied. The presence of axons crossing suture lines was sought histologically. Results: Nerves were identified crossing suture lines. Electrical or chemical (ie, nicotine or angiotensin II) activation of sympathetic efferent neurons enhanced cardiodynamics, as did tyramine. Stimulating vagal efferent preganglionic axons induced bradycardia in half of the dogs. Functional reinnervation did not correlate with specific power spectra derived from rate variability in the conscious state. Responding to nicotine and angiotensin II in situ, transplanted intrinsic cardiac neurons generated spontaneous activity. These neurons displayed nicotine-dependent synaptic inputs in vitro. Ventricular tissue had normal beta-adrenergic receptor affinity and density but reduced catecholamine and alpha-tubulin contents. Conclusions: The intrinsic cardiac nervous system receives reduced input from extracardiac sympathetic efferent neurons after transplantation and inconsistent input from parasympathetic efferent preganglionic neurons. These heterogeneous neuronal inputs are not reflected in heart rate variability or ventricular beta-adrenergic receptor function. Transplanted angiotensin II-sensitive intrinsic cardiac neurons exert greater cardiac control than do nicotine-sensitive ones. The intrinsic cardiac nervous system remodels itself after cardiac transplantation, and this indicates that direct assessment of extracardiac and intrinsic cardiac neuronal behavior is required to fully understand cardiac control after transplantation.
Article
The cytoplasmic polyadenylation element-binding protein 3 (CPEB3), a regulator of local protein synthesis, is the mouse homolog of ApCPEB, a functional prion protein in Aplysia. Here, we provide evidence that CPEB3 is activated by Neuralized1, an E3 ubiquitin ligase. In hippocampal cultures, CPEB3 activated by Neuralized1-mediated ubiquitination leads both to the growth of new dendritic spines and to an increase of the GluA1 and GluA2 subunits of AMPA receptors, two CPEB3 targets essential for synaptic plasticity. Conditional overexpression of Neuralized1 similarly increases GluA1 and GluA2 and the number of spines and functional synapses in the hippocampus and is reflected in enhanced hippocampal-dependent memory and synaptic plasticity. By contrast, inhibition of Neuralized1 reduces GluA1 and GluA2 levels and impairs hippocampal-dependent memory and synaptic plasticity. These results suggest a model whereby Neuralized1-dependent ubiquitination facilitates hippocampal plasticity and hippocampal-dependent memory storage by modulating the activity of CPEB3 and CPEB3-dependent protein synthesis and synapse formation.
Article
There have been great advances in the neurological sciences in recent years including some in the higher functions of the brain such as memory but one of the more critical of these with close ties to memory is consciousness which remains an enigma. Revolutionary developments in genetics during the last two decades, referred to as epigenetics, have provided opportunity for discovery. The chromatin in the cell nucleus consists mainly of DNA nucleotides and histone proteins and the DNA is dynamically and epigenetically altered by the local actions of enzymes and trans-acting factors on the adjacent histone amino acids. DNA is also directly activated or inhibited by methyl groups and by non-coding RNAs. Epigenetics is a determinant in long-term cell memory consolidation and, as recently demonstrated in animal and human studies and described here, these effects enable a rapid and extraordinarily complex cognitive matching of cell memory to experience during consciousness.
Article
Although the critical role for epigenetic mechanisms in development and cell differentiation has long been appreciated, recent evidence reveals that these mechanisms are also employed in postmitotic neurons as a means of consolidating and stabilizing cognitive-behavioral memories. In this review, we discuss evidence for an "epigenetic code" in the central nervous system that mediates synaptic plasticity, learning, and memory. We consider how specific epigenetic changes are regulated and may interact with each other during memory formation and how these changes manifest functionally at the cellular and circuit levels. We also describe a central role for mitogen-activated protein kinases in controlling chromatin signaling in plasticity and memory. Finally, we consider how aberrant epigenetic modifications may lead to cognitive disorders that affect learning and memory, and we review the therapeutic potential of epigenetic treatments for the amelioration of these conditions.
Article
Quality of life (QoL) studies in heart transplant recipients generally rely on quantifiable self-report questionnaires and have shown that approximately 20% of patients undergo distress and poor QoL not clearly related to medical variables. Building on existing qualitative research, we used a phenomenologically informed audiovisual method to explore the nature of "distress" in heart transplant recipients. Focused open-ended interviews were conducted in non-clinical settings with 27 medically stable heart transplant recipients (70% male, mean age 53 ± 13 years, range 18 to 72 years; mean time since transplant 4.1 ± 2.4 years). Interviews were audio/videotaped and transcribed verbatim. A qualitative software program (NVIVO8) was used to code interview transcripts and videotaped bodily gestures and "expressive artifacts" as well as vocal tone and volume. Distress was displayed by 88% of patients during the interview, and 52% displayed a profound disjunct between the words they used to describe their quality of life (e.g., "wonderful") and their embodied expressions of the same (e.g., protective body posturing, distressed facial expression). Most also expressed significant distress when discussing issues such as the donor and their "gift of life," as well as a disrupted sense of bodily integrity and identity that they felt could only be appreciated by fellow heart recipients. Increased awareness of this distress and disruption related to bodily integrity and identity after heart transplant may allow transplant professionals and researchers to see beyond "words" to more effectively reduce distress and improve quality of life.
Article
Heart transplantation is not simply a question of replacing an organ that no longer functions. The heart is often seen as source of love, emotions, and focus of personality traits. To gain insight into the problem of whether transplant patients themselves feel a change in personality after having received a donor heart, 47 patients who were transplanted over a period of 2 years in Vienna, Austria, were asked for an interview. Three groups of patients could be identified: 79% stated that their personality had not changed at all postoperatively. In this group, patients showed massive defense and denial reactions, mainly by rapidly changing the subject or making the question ridiculous. Fifteen per cent stated that their personality had indeed changed, but not because of the donor organ, but due to the life-threatening event. Six per cent (three patients) reported a distinct change of personality due to their new hearts. These incorporation fantasies forced them to change feelings and reactions and accept those of the donor. Verbatim statements of these heart transplant recipients show that there seem to be severe problems regarding graft incorporation, which are based on the age-old idea of the heart as a centre that houses feelings and forms the personality.
Article
For the patient, heart transplantation means more than an operation; adjustment to its rigors requires a high degree of personal strength and adequacy of coping skills. The goal of our study was to gain insight into how heart transplant patients cope with the fact that their own heart has been replaced by a donor organ from an unknown dead donor who was the target of disease, accident, or even suicide. Over a period of 2 years 44 transplant patients were interviewed after rehabilitation in a semi-structured interview regarding their feelings about and reactions to the graft and the donor. Their answers were recorded, transcribed, and analyzed as to content. Three groups of patients were identified: (1) the complete deniers (N = 15), who denied thinking about the donor; (2) the partial deniers (N = 17), who were aware of avoiding thinking about the donor; and those who coped (N = 12), who accepted the death of the donor as reality and also reported having more or less close connections with the donor. Eighty-two percent of the patients interviewed accepted the donor heart immediately as their own, whereas the remaining 18% avoided talking and thinking about the graft and donor. The findings are supported by verbatim statements of patients. The role of defense mechanisms in heart transplant patients is discussed.
Article
Sexual concerns after heart transplantation are commonly experienced yet seldom voiced. Forty-five patients approved for this procedure were surveyed regarding sexual issues. Twenty-one (47%) persons responded, of whom 16 had undergone heart transplantation, and five were waiting for a donor. Sexual dysfunction included impotence, ejaculation problems, altered libido, and avoidance of sexual opportunities. Contributing factors to these sexual difficulties were fear of death during coitus, effects of medication on interest and ability to function, body-image concerns, depression, uncertainty about the sexuality of the donor, and altered roles and responsibilities within the family. Recommendations for members of heart transplant teams include (1) obtaining a routine sexual history during the evaluation of candidates, (2) heightening awareness of the sexual concerns of these persons, (3) aggressively treating clinical depression, (4) establishing peer support groups for spouses of transplant patients, (5) presenting didactic material on sexual issues after transplant, (6) adjusting medications when sexual problems arise, and (7) addressing one's own level of comfort in discussing sex-related topics with transplant patients.
Article
Cardiac transplantation is viable therapeutic alternative for patients with end-stage heart disease, which offers a favourable short- and medium-term prognosis. The survival has improved from 20% of patients who survived at one year after transplantation in the 1960s to the present figures of 80%-85% of patients who are alive at one year, and 50%-70% of patients who are alive at five years, after transplantation. Therefore, it seems timely to focus attention on the psychological well-being of cardiac-transplant recipients. The medical literature is scant in regard to the psychiatric and the psychosocial impact of cardiac transplantation on recipients, and a systematic and prospective study of the psychosocial adaptation of recipients is lacking. Since 1984, we have been studying the emotional impact of cardiac transplantation on recipients and their families. This article presents the results for a group of recipients who have been assessed before transplantation, then followed-up at discharge from hospital and at four, eight and 12 months after transplantation. The study attempted to quantitate the recipients' anxiety, depression, body image and subjective quality of life by way of standardized self-assessment questionnaires. The recipients' satisfaction with relationships or their marital situation also was reported, as were their degree of rehabilitation at 12 months and their attitudes to various aspects of treatment after the transplantation. Before the transplantation, 53% of patients reported an increase in anxiety and 34% of patients recorded scores that indicated mild-to-moderate levels of depression. Thirty-seven per cent of patients showed a deterioration in the quality of their lives and 34% of patients had a negative body image. After the transplantation, significant improvements occurred in all parameters, which were maintained at follow-up.
Article
This study was designed to assess aspects of the quality of life and rehabilitation of heart transplant recipients who had transplantations at St. Vincent's Hospital, New South Wales, Australia, between February 1984 and March 1987. Factors determining return to full-time employment were delineated. A questionnaire was sent to 51 recipients. The response rate was 92%. The questionnaire measured employment status and satisfaction with family, social, marital, and sexual life. Financial status, exercise ability, and participation in daily activities were also assessed. Analysis showed that 53% of recipients had returned to either full-time or part-time employment, home duties, or full-time study. A further 28% were receiving a pension, 9% had chosen voluntary retirement, 6% were receiving unemployment benefits, and 4% were getting paid leave. Ability to exercise was improved for 77% of recipients and remained the same for another 14%. Financial status was unchanged for 45% and improved for 17%. Thirty-eight percent believed that they were worse off financially. Ratings of social, family, and marital life showed nearly complete or complete satisfaction in most cases. Satisfaction with sex life was less favorable. Comparison of the group who had returned to full-time employment with the group receiving a pension identified two variables of work status--length of time since transplantation and employment status before transplantation. There were also some differences between the two groups on quality of life ratings.
Article
Psychodiagnostic data are reported on 69 heart transplant candidates. Twenty-seven patients actually received a transplantation. A high prevalence of anxiety and depression appeared related to their desperate cardiac status. Distressful symptoms did not predict postoperative psychiatric complications. Reduced coping skills as reflected by diagnoses of personality disorders or organic mental impairment were associated with many behavioral problems capable of jeopardizing survival. Psychiatric input is necessary for, and was helpful in, the management of these patients.
Article
This paper explores the problems of benefit measurement in the economic evaluation of heart transplant programmes. We present data from our evaluation of the U.K. heart transplant programmes on both survival and quality of life and we examine the relationship between the two. The quality of life measure used, the Nottingham Health Profile (NHP), is described and results presented. We attempt to aggregate this profile measure into a single index score and combine these data with life expectancy gains to produce estimates of Quality Adjusted Life Years (QALYs) gained for heart transplantation. In addition we examine the extent to which pre-transplant NHP scores can be used as predictors of post-transplant survival.
Article
Heart transplantation necessarily involves allocation of a scarce resource. Seventy candidates for the operation were evaluated by a psychiatrist providing consultation for a transplantation team. Thirteen patients were determined to be unsuitable for the surgery owing to psychiatric factors. The psychiatric recommendation to the team for selection or nonselection was based on evaluation of the patient's ability to overcome such challenges of transplantation as waiting for a donor, psychological incorporation of the new organ, and, especially, compliance with the medical regimen. Certain DSM-III diagnoses proved to be major impediments to patient selection. Based on their experience, the authors present specific recommendations for assessing candidates.