Chronic myeloid leukemia (CML) is a cancer of the hematopoietic system initiated by a single genetic mutation which results in the oncogenic fusion protein Bcr-Abl. Untreated, patients pass through different phases of the disease beginning with the rather asymptomatic chronic phase and ultimately culminating into blast crisis, an acute leukemia resembling phase with a very high mortality. Although many processes underlying the chronic phase are well understood, the exact mechanisms of disease progression to blast crisis are not yet (...) revealed. In this paper we develop a mathematical model of CML based on causal Bayesian networks in order to study possible disease progression mechanisms. Our results indicate that an increase of Bcr-Abl levels alone is not sufficient to explain the phenotype of blast crisis and that secondary changes such as additional mutations are necessary to explain disease progression and the poor therapy response of patients in blast crisis. (shrink)

The fight to find effective, long-lasting treatments for cancer has led many researchers to consider protein degrading entities. Recent developments in PROteolysis TArgeting Chimeras (PROTACs) have signified their potential as possible cancer therapies. PROTACs are small molecule, protein degraders that function by hijacking the built-in Ubiquitin-Proteasome pathway. This review mainly focuses on the general design and functioning of PROTACs as well as current advancements in the development of PROTACs as anticancer therapies. Particular emphasis is given to PROTACs designed against various (...) types of Leukemia/Blood malignancies. (shrink)

Acute Myeloid Leukemia is a kind of fatal blood cancer with a high death rate caused by abnormal cells’ rapid growth in the human body. The usual method to detect AML is the manual microscopic examination of the blood sample, which is tedious and time-consuming and requires a skilled medical operator for accurate detection. In this work, we proposed an AlexNet-based classification model to detect Acute Myeloid Leukemia in microscopic blood images and compared its performance with LeNet-5-based model (...) in Precision, Recall, Accuracy, and Quadratic Loss. The experiments are conducted on a dataset of four thousand blood smear samples. The results show that AlexNet was able to identify 88.9% of images correctly with 87.4% precision and 98.58% accuracy, whereas LeNet-5 correctly identified 85.3% of images with 83.6% precision and 96.25% accuracy. (shrink)

B‐cell acute lymphoblastic leukaemia (B‐ALL) is a clonal malignant disease originated in a single cell and characterized by the accumulation of blast cells that are phenotypically reminiscent of normal stages of B‐cell differentiation. B‐ALL origin has been a subject of continuing discussion, given the fact that human disease is diagnosed at late stages and cannot be monitored during its natural evolution from its cell of origin, although most B‐ALLs probably start off with chromosomal changes in haematopoietic stem cells. However, the (...) cells responsible for maintaining the disease appear to differ between the different types of B‐ALLs and this remains an intriguing and exciting topic of research, since these cells have been posited to be responsible for resistance to conventional therapies, recurrence and dissemination. During the last years this problem has been addressed primarily by transplantation of purified subpopulations of human B‐ALL cells into immunodeficient mice. The results from these different reconstitution experiments and their interpretations are compared in this review in the context of normal B‐cell developmental plasticity. While the results from different research groups might appear mutually exclusive, we discuss how they could be reconciled with the biology of normal B‐cells and propose research avenues for addressing these issues in the future. (shrink)

Throughout this paper PJ Kearney attempts to balance the risks and benefits of different approaches in paediatric oncology. Decisions have to be considered both in the short and the long term. Where religious beliefs, such as those held by Jehovah's Witnesses in relation to blood transfusions, conflict with normal medical practice the decision is often removed from the doctor, parents or patient to the courts. This sort of solution can be counter-productive, especially as good health care and subsequent recovery rely, (...) to a large extent, on good relationships between and among the parties concerned. Destruction of these relationships, for whatever reason, often has a detrimental effect on the patient, in whose best interest everyone believes they are acting. (shrink)

The ability to improve diagnosis and refine prognosis in children with acute leukaemia is improving steadily. A growing number of tests can and are being performed on leukaemic cells. These include surface-marker analysis, DNA content, cytogenetics and studies of gene rearrangements. Increasingly large bone-marrow samples, now usually obtained under general anaesthesia, are required to make secure diagnoses. Ethical issues arise from three major areas. 1) Current research on leukaemia cells requested by the Medical Research Council is considered by local research (...) ethics committees, but parents are not regularly given detailed information about or asked specifically to consent to such research; 2) substantial quantities of excess cells are stored indefinitely. This archive of stored material is a valuable resource for research but there has been little consideration of the ethical issues which arise from this practice, and 3) there is a potential for pressure to obtain increasingly large samples. 'Creeping growth' in sample size is likely to continue unless ethics committees consider future research proposals in more detail. These issues deserve attention in order that worthwhile research and its publication are not impeded for want of ethical consideration. The implications extend beyond the field of childhood leukaemia. (shrink)

Mutations in the CEBPA gene are present in 10–15% of acute myeloid leukemia (AML) patients. The most frequent type of mutations leads to the expression of an N‐terminally truncated variant of the transcription factor CCAAT/enhancer‐binding protein alpha (C/EBPα), termed p30. While initial reports proposed that p30 represents a dominant‐negative version of the wild‐type C/EBPα protein, other studies show that p30 retains the capacity to actively regulate gene expression. Recent global transcriptomic and epigenomic analyses have advanced the understanding of the (...) distinct roles of the p30 isoform in leukemogenesis. This review outlines direct and indirect effects of the C/EBPα p30 variant on oncogenic transformation of hematopoietic progenitor cells and discusses how studies of N‐terminal CEBPA mutations in AML can be extrapolated to identify novel gain‐of‐function features in oncoproteins that arise from recurrent truncating mutations in transcription factors. (shrink)

Mixed lineage leukemia (MLL) fusion protein (FP)‐induced acute leukemia is highly aggressive and often refractory to therapy. Recent progress in the field has unraveled novel mechanisms and targets to combat this disease. Menin, a nuclear protein, interacts with wild‐type (WT) MLL, MLL‐FPs, and other partners such as the chromatin‐associated protein LEDGF and the transcription factor C‐Myb to promote leukemogenesis. The newly solved co‐crystal structure illustrating the menin–MLL interaction, coupled with the role of menin in recruiting both WT MLL (...) and MLL‐FPs to target genes, highlights menin as a scaffold protein and a central hub controlling this type of leukemia. The menin/WT MLL/MLL‐FP hub may also cooperate with several signaling pathways, including Wnt, GSK3, and bromodomain‐containing Brd4‐related pathways to sustain MLL‐FP‐induced leukemogenesis, revealing new therapeutic targets to improve the treatment of MLL‐FP leukemias. (shrink)

Abstractβ‐Catenin/CTNNB1 is critical for leukemia initiation or the stem cell capacity of several hematological malignancies. This review focuses on a general evaluation of β‐catenin function in normal T‐cell development and T‐cell acute lymphoblastic leukemia (T‐ALL). The integration of the existing literature offers a state‐of‐the‐art dissection of the complexity of β‐catenin function in leukemia initiation and maintenance in both Notch‐dependent and independent contexts. In addition, β‐catenin mutations are screened for in T‐ALL primary samples, and it is found that (...) they are rare and with little clinical relevance. Transcriptional analysis of Wnt family members (Ctnnb1, Axin2, Tcf7, and Lef1) and Myc in different publicly available T‐ALL cohorts indicates that the expression of these genes may correlate with T‐ALL subtypes and/or therapy outcomes. (shrink)

The Gardner report, recently published in the UK, showing a correlation between incidence of childhood leukaemia and paternal exposure to ionising radiations (amongst fathers working in nuclear power plants) has added a new element to debates about both the risk factors in nuclear power plants and the relationships between ionising radiations and leukaemogenesis. The epidemiologic and genetic evidence concerning leukaemias is reviewed here and it is concluded that the leukaemogenic agent, whose existence is indicated in the Gardner report, is unlikely (...) to be paternal radiation dose per se but rather exposure to another factor that is correlated with paternal radiation dose received. (shrink)

The theoretical rationale was the author’s Functional Model of Health, where health is construed as a function of creative coping with stress. Participants in the study were 141 patients with blood cancer treated with bone marrow transplantation at the Hematology Clinic, Jagiellonian University Collegium Medicum. Besides a standardized interview the following instruments were used: STAI by Spielberger, CISS and CHIP by Endler and Parker, and SOC-29 by Antonovsky. Health status was operationalized using 10-point self-rating scales to assess the patients’ perceived (...) health and sense of calmness, while their objective health was rated by a medical expert - hematologist. In the statistical analyses significant correlations were found between stress level and the patients’ subjective health. The following variables predicted stress intensity: anxious personality, distraction coping strategy, female sex, and sense of meaningfulness. Subjective health predictors of leukemia patients are: objective health, level of stress, by the patient’s sense of meaningfulness and focusing on negative emotions. To promote patients’ health moreover, their sense of meaningfulness in life and in being active should be supported and enhanced. (shrink)

Hematopoiesis is the complex developmental process through which undifferentiated, pluripotent, hematopoietic stem cells come to generate mature, functional blood cells. This process is regulated in large part by specific transcription factors that control expression of genes necessary for the developmental sequence. Leukemias represent one form of disruption of this normal developmental process, and studies over the past few years have shown that many of the genes that underlay leukemogenesis are also essential for normal hematopoiesis. In an interesting recent example, Song (...) et al.(1) demonstrate that haploinsufficiency of the AML1 gene is the genetic basis of a form of familial thrombocytopenia which predisposes the affected individuals to the development of acute myeloid leukemia. Here we summarize Song's paper and current information describing the interesting dosage effects of this gene and other members of its gene family. BioEssays 22:214–218, 2000. © 2000 John Wiley & Sons, Inc. (shrink)

A human retrovirus etiologically related to a unique leukemia, adult T‐cell leukemia, has been discovered. This retrovirus is endemic in certain areas and ethnic groups, such as the Japanese in Japan and Blacks in Africa. The virus is transmitted from mother to child and husband to wife and by blood transfusion. In addition, a virus like the human retrovirus has been found in various species of monkeys in Asia and Africa. This review describes and discusses recent results on (...) the natural history of these primate lymphotropic retroviruses. (shrink)

The DNA hypomethylating agents (HMA) azacitidine (AZA) and decitabine (DAC) improve survival and transfusion independence in myelodysplastic syndrome (MDS) and enable a low intensity cytotoxic treatment for aged AML patients unsuitable for intensive chemotherapy, particularly in combination with novel agents. The proposed mechanism of AZA and DAC relies on active DNA replication and therefore patient responses are only observed after multiple cycles of treatment. Although extended dosing may provide the optimal scheduling, the reliance of injectable formulation of the drug limits (...) it to intermittent treatment. Recently, an oral formulation of AZA demonstrated significantly improved patient relapse free survival (RFS) and overall survival (OS) when used as maintenance after chemotherapy for AML. In addition, both DAC and AZA were found to be highly effective to improve survival in elderly patients with AML through combination with other drugs. These recent exciting results have changed the therapeutic paradigm for elderly patients with AML. In light of this, we review current knowledge on HMA mechanism of action, clinical trials exploring dosing and scheduling, and recent HMA combination therapies to enhance efficacy. (shrink)

Objective: This study examined the process through which elderly patients with new-onset acute leukemia make treatment decisions from the time of diagnosis, in order to identify factors influencing this decision-making process in Japan. Methods: Semi-structured interviews were conducted with twenty-two elderly patients with leukemia. The data were analyzed using the modified grounded theory approach. Results: The process of decision-making in elderly patients with leukemia includes three stages: Initial reactions at diagnosis, change in attitudes, and entrusting the physician (...) with the treatment plan. Initial reactions at diagnosis were affected by interactions with others that brought peace of mind to the patients. Change in attitudes was affected by encouragement from others to undergo treatment and their own motivation to face treatment. Patients came to entrust their treatment plan completely to their physician, because they wanted to feel relief and did not want to have to grapple with difficult medical information that was relevant to decision-making about their disease and treatment options. Conclusions: The process of decision-making in elderly patients with leukemia is affected by several factors and included three stages. Our present study findings can provide suggestions on how medical professionals might better support the process of decision-making in elderly patients with leukemia. (shrink)

This study described parent participation in the informed consent conference for randomized clinical trials (RCTs) in childhood leukemia and documented the relationship of physician communication to parent participation. Parents of 140 children with newly diagnosed leukemia who were eligible for RCTs were studied at six sites using comprehensive methods involving direct observation and transcripts of parent-physician communication based on audiotapes. Parent participation during the informed consent conference reflected a wide range of content categories. Consistent with hypotheses, Physician Rapport (...) and Partnership Building related to parent participation in the informed consent conference but Information Giving did not. Higher parent socioeconomic status also was related to greater parent participation for two of three measures of parent participation. Findings suggest that physician behaviors that provide support and facilitate communication may enhance parental participation in the informed consent conference for RCTs in childhood leukemia. (shrink)

Cell lines and cell samples from patients provide opportunities for studying the mechanisms of leukemic cellular differentiation and proliferation. Phorbol esters and 1,25 dihydroxy vitamin D3 can induce differentiation of myeloid leukemic cells to macrophages. Differentiation to granulocytes can be induced by several different compounds. Myeloid differentiation is associated closely with the alteration in expression of several oncogenes. These regulatory events may be associated with the extent of methylation, unfolding or association of chromatin to the nuclear matrix. Oncogene amplification, mutation, (...) or deletion can occur with malignant transformation. Future studies point to the development of specific pharmacological agents which can modify the neoplastic transformation. (shrink)

Diagnostik und Klassifikation der akuten myeloischen Leukämie (AML) beruhen auf zytologischen und zytogenetischen Charakteristika. Eine Individualisierung der Diagnostik und Therapie wird für AML mit normalem Karyotyp (CN-AML) durch den Nachweis spezifischer Genmutationen zunehmend ermöglicht. In einem systematischen Literaturreview und Metanalyse wurde die Mutation FLT3-ITD bei CN-AML untersucht. Eine systematische Literaturrecherche aller Veröffentlichungen der Datenbanken Embase, Pubmed, Healthstar, BIOSIS, ISI Web of Knowledge und Cochrane wurde für den Zeitraum 2000 bis März 2012 im Hinblick auf die Mutation FLT3-ITD bei Patienten mit (...) CN-AML und einem Alter von 15–65 Jahren durchgeführt. Der Literaturrecherche folgte eine Literaturselektion, eine Datenextraktion und eine qualitative sowie quantitative Informationssynthese in Form einer Metaanalyse. Achtzehn Veröffentlichungen konnten in die qualitative Analyse zur CN-AML eingeschlossen werden. Daten von 3 Publikationen zum Gesamtüberleben mit insgesamt 1.203 Patienten gingen mit Bezug auf den Marker FLT3-ITD in die Metaanalyse ein. Für FLT3-ITD zeigte sich eine statistisch signifikante schlechtere Prognose mit einer hazard ratio von 2,19 für das Gesamtüberleben bei CN-AML. FLT3-ITD ist im Vergleich zum Wildtyp mit einer schlechteren Prognose in Bezug auf den Krankheitsverlauf bei AML assoziiert. Die Analyse von FLT3 sollte bei der AML berücksichtigt werden. (shrink)

While outcomes for children with T-cell acute lymphoblastic leukemia have improved dramatically, survival rates for patients with relapsed/refractory disease remain dismal. Prior studies indicate that glucocorticoid resistance is more common than resistance to other chemotherapies at relapse. In addition, failure to clear peripheral blasts during a prednisone prophase correlates with an elevated risk of relapse in newly diagnosed patients. Here we show that intrinsic GC resistance is present at diagnosis in early thymic precursor T-ALLs as well as in a (...) subset of non-ETP T-ALLs. GC-resistant non-ETP T-ALLs are characterized by strong induction of JAK/STAT signaling in response to interleukin-7 stimulation. Removing IL7 or inhibiting JAK/STAT signaling sensitizes these T-ALLs, and a subset of ETP T-ALLs, to GCs. The combination of the GC dexamethasone and the JAK1/2 inhibitor ruxolitinib altered the balance between pro- and anti-apoptotic factors in samples with IL7-dependent GC resistance, but not in samples with IL7-independent GC resistance. Together, these data suggest that the addition of ruxolitinib or other inhibitors of IL7 receptor/JAK/STAT signaling may enhance the efficacy of GCs in a biologically defined subset of T-ALL.Leukemia advance online publication, 30 May 2017; doi:10.1038/leu.2017.136. (shrink)

Cancer is an evolutionary and ecological process in which complex interactions between tumour cells and their environment share many similarities with organismal evolution. Tumour cells with highest adaptive potential have a selective advantage over less fit cells. Naturally occurring transmissible cancers provide an ideal model system for investigating the evolutionary arms race between cancer cells and their surrounding micro‐environment and macro‐environment. However, the evolutionary landscapes in which contagious cancers reside have not been subjected to comprehensive investigation. Here, we provide a (...) multifocal analysis of transmissible tumour progression and discuss the selection forces that shape it. We demonstrate that transmissible cancers adapt to both their micro‐environment and macro‐environment, and evolutionary theories applied to organisms are also relevant to these unique diseases. The three naturally occurring transmissible cancers, canine transmissible venereal tumour (CTVT) and Tasmanian devil facial tumour disease (DFTD) and the recently discovered clam leukaemia, exhibit different evolutionary phases: (i) CTVT, the oldest naturally occurring cell line is remarkably stable; (ii) DFTD exhibits the signs of stepwise cancer evolution; and (iii) clam leukaemia shows genetic instability. While all three contagious cancers carry the signature of ongoing and fairly recent adaptations to selective forces, CTVT appears to have reached an evolutionary stalemate with its host, while DFTD and the clam leukaemia appear to be still at a more dynamic phase of their evolution. Parallel investigation of contagious cancer genomes and transcriptomes and of their micro‐environment and macro‐environment could shed light on the selective forces shaping tumour development at different time points: during the progressive phase and at the endpoint. A greater understanding of transmissible cancers from an evolutionary ecology perspective will provide novel avenues for the prevention and treatment of both contagious and non‐communicable cancers. (shrink)

Stem cells and their malignant counterparts require the support of a specific microenvironment or “niche”. While various anti‐cancer therapies have been broadly successful, there are growing opportunities to target the environment in which these cells reside to further improve therapeutic efficacy and outcome. This is particularly true when the aim is to target normal or malignant stem cells. The field aiming to target or use the niches that harbor, protect, and support stem cells could be designated as “nichotherapy”. In this (...) essay, we provide a few examples of nichotherapies. Some have been employed for decades, such as hematopoietic stem cell mobilization, whereas others are emerging, such as chemosensitization of leukemia stem cells by targeting their niche. (shrink)

Stem cells and their malignant counterparts require the support of a specific microenvironment or “niche”. While various anti‐cancer therapies have been broadly successful, there are growing opportunities to target the environment in which these cells reside to further improve therapeutic efficacy and outcome. This is particularly true when the aim is to target normal or malignant stem cells. The field aiming to target or use the niches that harbor, protect, and support stem cells could be designated as “nichotherapy”. In this (...) essay, we provide a few examples of nichotherapies. Some have been employed for decades, such as hematopoietic stem cell mobilization, whereas others are emerging, such as chemosensitization of leukemia stem cells by targeting their niche. (shrink)

Promyelocytic leukaemia nuclear bodies (PML NBs) are generally present in all mammalian cells, and their integrity correlates with normal differentiation of promyelocytes. Mice that lack PML NBs have impaired immune function, exhibit chromosome instability and are sensitive to carcinogens. Although their direct role in nuclear activity is unclear, PML NBs are implicated in the regulation of transcription, apoptosis, tumour suppression and the anti‐viral response. An emerging view is that they represent sites where multi‐subunit complexes form and where post‐translational modification of (...) regulatory factors, such as p53, occurs in response to cellular stress. Following DNA damage, several repair factors transit through PML NBs in a temporally regulated manner implicating these bodies in DNA repair. We propose that PML NBs are dynamic sensors of cellular stress, which rapidly disassemble following DNA damage into large supramolecular complexes, dispersing associated repair factors to sites of damage. The dramatically increased total surface area available would enhance interactions between PML‐associated factors regulating DNA repair and apoptosis. BioEssays 26:963–977, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

My little girl has leukemia; she has had it for over a year, and now she needs at least five pints of blood a day. Not the whole blood, just the platelets. Most of our relatives and friends have given at least a few times. But we need more. Now I have to go to strangers.So begins Roberta Silman's short story, “Giving Blood,” a story about illness and charity. When the narrator's husband solicited blood donations at his workplace, “he (...) thought everyone would help…He must have asked a hundred people. Thirty gave. His officemate…turned green and said, ‘Oh, no, anything but that. I'm scared of needles.'”. (shrink)

Although the promyelocytic leukemia (PML) protein is renowned for regulating a wide range of cellular processes and as an essential component of PML nuclear bodies (PML‐NBs), the mechanisms through which it exerts its broad physiological impact are far from fully elucidated. Here, we review recent studies supporting an emerging view that PML's pleiotropic effects derive, at least partially, from its role in regulating histone H3.3 chromatin assembly, a critical epigenetic mechanism. These studies suggest that PML maintains heterochromatin organization by (...) restraining H3.3 incorporation. Examination of PML's contribution to H3.3 chromatin assembly in the context of the cell cycle and PML‐NB assembly suggests that PML represses heterochromatic H3.3 deposition during S phase and that transcription and SUMOylation regulate PML's recruitment to heterochromatin. Elucidating PML’ s contributions to H3.3‐mediated epigenetic regulation will provide insight into PML's expansive influence on cellular physiology and open new avenues for studying oncogenesis linked to PML malfunction. (shrink)

According to the somatic mutation theory (SMT), cancer begins with a genetic change in a single cell that passes it on to its progeny, thereby generating a clone of malignant cells. It is strongly supported by observations of leukemias that bear specific chromosome translocations, such as Burkitt's lymphoma, in which a translocation activates the c‐myc gene, and chronic myeloid leukemia (CML), in which the Philadelphia chromosome causes production of the BCR‐ABL oncoprotein. Although the SMT has been modified and extended (...) to encompass tumor suppressor genes, epigenetic inheritance, and tumor progression through accumulation of further mutations, perhaps the strongest validation comes from the successful treatment of certain malignancies with drugs that directly target the product of the mutant gene.magnified imageDavid Vaux is at the Walter and Eliza Hall Institute and La Trobe Institute for Molecular Science, Melbourne, Australia. (shrink)

Love, fear, hope, calculus, and game shows-how do all these spring from a few delicate pounds of meat? Neurophysiologist Ian Glynn lays the foundation for answering this question in his expansive An Anatomy of Thought, but stops short of committing to one particular theory. The book is a pleasant challenge, presenting the reader with the latest research and thinking about neuroscience and how it relates to various models of consciousness. Combining the aim of a textbook with the style of a (...) popularization, it provides all the lay reader needs to know to participate in the philosophical debate that is redefining our attitudes about our minds. Drawing on the rich history of neurological case studies, Glynn picks through the building blocks of our nervous system, examines our visual and linguistic systems, and probes deeply into our higher thought processes. The stories of great scientists, like Ramon y Cajal, and famous patients, like Sperry's split-brained epileptics, illuminate the scientific issues Glynn selects as essential for understanding consciousness. Some might argue that his lengthy explorations of natural selection overemphasize evolutionary explanations of psychological phenomena, but they must also agree that evolutionary psychology has distanced itself mightily from social Darwinism in recent years and merits a reappraisal. The great consciousness debate may form the core of the 21st-century Zeitgeist; get ready for it with An Anatomy of Thought. -Rob Lightner From Publishers Weekly How do we know? What do we think? How could a philosophical problem-'the mind-body problem,' say-induce a headache? What can evolutionary theory, molecular biology, the history of medicine and experimental psychology tell us about the features of human consciousness, and (once again) how do we know? Glynn, a physician and Cambridge University professor, meticulously attempts to answer these questions and more, setting forth the results of all sorts of research relevant to our brains-from 19th-century dissections to Oliver Sacks-like case studies, work with monkeys and supercomputers, and the enduring puzzles of philosophy, which he rightly saves for near the end. After explaining evolution by natural selection and 'clearing away much dross,' Glynn lays out the experiments and theories that have shown 'how nerve cells can carry information about the body, how they can interact' and how sense organs work; demonstrates the 'mixture of parallel and hierarchical organization' in our brains and 'the striking localization of function within it'; considers where neuroscience is likely to go; and admits that, among the many fields of exciting research just ahead, 'we can be least confident of progress toward a complete, scientific explanation of our sensations and thoughts and feelings.' Other recent explaining-the-brain books have sometimes advanced simplistic, or implausibly grand, claims about the nature and features of consciousness in general. Instead, Glynn offers a patient, informative, well-laid-out researcher's-eye view of what we have learned, how we figured it out and what we still don't know about neurons, senses, feelings, brains and minds. (Apr.) Copyright 2000 Reed Business Information, Inc. From Library Journal The nature of consciousness, which perennially troubles the minds of scientists and philosophers, is the subject of an ever-growing body of literature. Two of the latest entries approach the topic from different perspectives. Glynn, a professor of physiology and head of the Physiological Laboratory at Cambridge, offers a comprehensive summary of what we know about the brain-both its evolution and its mechanisms. Among the topics he covers are natural selection, molecular evolution, nerves and the nervous system, sensory perception, and the specific structures responsible for our intellect. Using the mechanisms involved in vision and speech as models, Glynn skillfully describes various neurological deficiencies that can lead to 'disordered seeing' and problems with the use of language. He carefully distinguishes what we know through experimental evidence from what we know through the observation of patients with neurological damage. He also describes some of the major theories that attempt to explain why these structures arose. While his book concentrates on the structures that make up the mind, Glynn is well aware that some physical events appear explicable only in terms of conscious mental events-a situation that conflicts with the laws of modern physics. Only briefly, however, does he consider the various approaches that have been taken to deal with the issues of mind/body and free will. In contrast, this is the primary focus of The Physics of Consciousness. After reviewing the fundamentals of classic physics, Walker (who has a Ph.D. in physics) summarizes elements of the new physics in which our knowledge of space, time, matter, and energy are all dependent on the moment of observation. Walker explores the meaning of consciousness as a characteristic of the observer. In this context both the observer and the act of measurement are critical. In essence, Walker leads his reader on a journey through his concept of a 'quantum mind,' which can both affect matter (including other minds) and can be affected by other distant matter/minds. To break up what would otherwise be an extremely dense text, Walker also relates the very touching story of the loss of his high-school sweetheart to leukemia. Indeed, it is his memory of their relationship that drives Walker to seek an understanding of ultimate reality. At times, he has a tendency to be dogmatic-as when he concludes, 'our consciousness, our mind, and the will of God are the same mind.' While An Anatomy of Thought is appropriate for most academic libraries, the Physics of Consciousness will be most accessible to readers with some knowledge of advanced physics. -Laurie Bartolini, Illinois State Lib., Springfield Copyright 2000 Reed Business Information, Inc. From Booklist The codiscoverers of natural selection-Charles Darwin and Alfred Wallace-disagreed over the possibility of finding an evolutionary explanation for the human mind. Glynn here argues Darwin's side of the debate, tracing an eons-long path of development starting from simple amino acids floating in primal seas and extending through the erect hominids in which the powers of a massive brain first manifest themselves. Patiently adducing evidence of an evolutionary origin for the underlying molecular machinery, Glynn dissects the nerve centers that make possible speech and hearing, sight, and reading. Pressing deeper, he lays bare the cortical foundations of personality. But those who deal with the mind must attend also to the arguments advanced by philosophers. And it is when he turns from dendrites to syllogisms (especially the vexing mind-body paradox) that Glynn's empirical reasoning fails him. In the end, he concedes his perplexity in trying to conceive of an evolutionary origin for human consciousness. This concession may set the shade of Alfred Wallace to chortling, but it will draw readers into an honest confrontation with a profound enigma. Bryce Christensen. (shrink)

Since the birth of the first test-tube baby, Louise Brown, in 1977, we have seen truly remarkable advances in biotechnology. We can now screen the fetus for Down Syndrome, Spina Bifida, and a wide range of genetic disorders. We can rearrange genes in DNA chains and redirect the evolution of species. We can record an individual's genetic fingerprint. And we can potentially insert genes into human DNA that will produce physical warning signs of cancer, allowing early detection. In fact, biotechnology (...) has progressed to such a point that virtually any kind of genetic manipulation, if not already possible, is just around the corner. But these breakthroughs also raise serious ethical and moral dilemmas that we are only now beginning to confront. In Wonderwoman and Superman, noted medical ethicist John Harris offers the first thorough analysis of the moral dilemmas created by the revolution in molecular biology. Covering a wide array of recent innovations, Harris discusses, for example, the moral decisions involved and the consequences of creating egg and embryo banks. Who should be allowed to use such resources? Should recipients be screened? Should such banks be open for public or private use? And does it cheapen life to make embryos available for sale? In another chapter, Harris examines the question of conceiving children chiefly for organ donation, focusing on the recent case of a woman who wanted to have a second child to provide a bone marrow donor for her first child sick with leukemia (she intended to abort the fetus if its bone marrow did not genetically match that of her living child). In this case, the medical staff had to decide whether they should perform in-vitro fertilization, knowing that the mother did not satisfy the clinic's criteria (there was no father), and also knowing the potential for abortion. Discussing the ethics of the mother's choice and the clinic's choice, Harris asks whether it is morally correct to create a child as an organ donor, whether the future child would suffer, whether it is worth any suffering to be born, and who has the right to weigh the various factors (both moral and physiological) involved in making these decisions. Delving into a multitude of issues such as when life begins, when suffering is needless, and whether we should play God, Wonderwoman and Superman provides not only a thought-provoking inquiry into the potential and actual ethical dilemmas created by the many advances in biotechnology, but challenges us to learn to choose responsibly and to face the moral implications of the choices that confront us. (shrink)

Does a human right to healthcare imply individual obligations to healthy behavior? Or put another way: Is a self-induced condition a relevant criterion for some sort of restriction of this right—like withholding or modifying treatment in circumstances where choices have to be made? For instance, should a drunk driver bear the costs of medical care that he needs after a car accident he has caused? Should there be a difference in healthcare entitlements between the smoker with a heart attack who (...) is seriously overweight and the 60-year old man who has always taken excellent care of himself and is suddenly stricken by leukemia? And how should we think about the risk-taking behavior of all the persons going on a skiing holiday or an exotic hiking trip? a. (shrink)

In 1999, a case was described on national television in which a woman had enlisted onto an international bone marrow registry with the altruistic desire to offer her bone marrow to some unidentified individual in need of a transplant. The potential donor then was notified that she was a compatible match with someone dying from leukemia and gladly donated her marrow, which cured the recipient of the disease. Years later, though, the recipient developed end-stage renal disease, a consequence of (...) the high-dose chemotherapy she received earlier to destroy her stem cells and prepare her for the bone marrow transplant. Finding a suitable donor for a kidney transplant proved extremely difficult. Desperate, she requested that the donor registry personnel help her locate the individual who earlier was determined to be a compatible donor and asked this now-identifiable individual to consider donating one of her two normally functioning kidneys for a kidney transplant. (shrink)

In 2008, researchers reported that Timothy Brown , a man with HIV infection and leukemia, received a stem-cell transplant that removed HIV from his body as far as can be detected. In 2013, an infant born with HIV infection received anti-retroviral treatment shortly after birth, but was then lost to the health care system for the next six months. When tested for HIV upon return, the child had no detectable viral load despite cessation of treatment. These remarkable clinical developments (...) have helped reinvigorate the field of ‘HIV cure’ research. (shrink)

This article examines how parents should make health decisions for one child when they may have a negative impact on the health interests or other interests of their siblings. The authors discuss three health decisions made by the parents of Alex Jones, a child with developmental disabilities with two older neurotypical siblings over the course of eight years. First, Alex’s parents must decide whether to conduct sequencing on his siblings to help determine if there is a genetic cause for Alex’s (...) developmental disabilities. Second, Alex’s parents must decide whether to move to another town to maximize the therapy options for Alex. Third, Alex’s parents must decide whether to authorize the collection of stem cells from Alex for a bone marrow transplant for his sibling who developed leukemia. We examine whether the consensus recommendations by Salter and colleagues (2023) regarding pediatric decision-making apply in families with more than one child. (shrink)

The protein tyrosine kinase activity of the v‐abl oncogene has been demonstrated to subvert the normal second messenger systems used by lymphoid cells for growth and differentiation. Transformation of bone marrow with the Abelson murine leukemia virus results in the appearance of B cell lineage cells arrested at the pre‐B cell stage. Recent reports have characterized these cells expressing high v‐abl kinase activity as deficient in detectable NF‐kB DNA binding activity and low level RAG gene expression. These observations suggest (...) that v‐abl may be inhibiting the differentiation of B cells by blocking these two crucial elements in the maturation pathway. (shrink)

Departing from a contemporary novel about a boy who is going to die from leukaemia, this article shows how the dimension of time can be seen as a morally relevant category that bridges both ‘dramatic’ issues, which constitute the dominant focus of bioethical decision making, and ‘undramatic’ issues, which characterize the lived experience of patients, relatives and health care workers. The moral task of comparing the various time dimensions of a given situation is explained as an act of ‘synchronizing’ the (...) clocks. Ethical sensitivity and competence are presented as core skills that allow a continuity of care in situations where dramatic issues seem to be resolved, but undramatic ones are still not addressed. A nine-step model of shared decision making is proposed as an approach to identifying critical junctures within an illness trajectory and synchronizing the clocks of the involved actors. (shrink)

This academic paper on Ethical issues of using umbilical cord blood stem cell therapy of John Stuart Mill perspective aim to investigate the new approaches in the treatment of diseases by using umbilical cord blood stem cells. And also to study ethical issues from the use of umbilical cord blood stem cells in the treatment of diseases considered by Mill’s utilitarianism. 21st century, the medical industry was interested in organ transplantation from stem cells especially stem cells from the umbilical cord (...) to treat chronic and degenerative organ diseases, blood cancer and organ transplantation which successful and widespread throughout the world. Thailand has about 900 new children with Leukemia every year. About 50 percent are leukemia which needs to be treated correctly and urgently. In general Standardized chemotherapy but if the cancer patient has a bad prognosis Or have recurrent cancer Patients need to be treated with bone marrow transplants or stem cells to have a chance to heal. According to Mill’s Utilitarianism, the ethical concepts that determine what is the basic criterion used to determine whether it should or should not concern with the popular benefit that the criterion used is the amount of happiness that results from actions. Treating the disease using stem cells will make the patient recover from the disease, healthier and happier in life. As Mill said "The correctness of an action depends on the tendency that the action will lead to happiness. (shrink)

Over the past two decades we have seen dramatic improvements in the efficacy, safety and availibity of antiretroviral therapy (ART). In the USA and Europe, life expectancy in people living with HIV disease approaches that of the HIV-uninfected.1 Even in regions hardest hit by the HIV epidemic, effective HIV therapy has reversed more than a decade of HIV-related decreased survival. Despite these advances in ART, motivations to pursue HIV cure remain strong due to the toxicity, adherence challenges, cost and access (...) to care issues associated with HIV therapy, as well as the persistant stigma associated with having HIV infection. Further and renewed motivation comes from a single case of HIV cure after stem cell transplantation for acute leukaemia. Given the tremendous improvements in ART, it is important to assess how effective and safe an HIV cure would need to be in order to be a viable option compared to ART. We argue that this should be done prior to the availability of a cure to provide realistic goals for researchers and policy makers. One methodology that has been increasingly popular over the past decade is the use of mathematical simulation modelling to assess the clinical impact, cost-effectiveness and clinical role of different treatment strategies in HIV disease, as well as in medicine broadly.2 Such models provide a framework and approach for using the best available data at any point in time, and assessing the potential impact of emerging innovations. Further, unlike individual trials focused on a single endpoint, these models can integrate multiple data sources to project beyond the timeline or outcomes of individual studies and project long-term outcomes in many domains, including virologic, immunologic, clinical and cost.3 Mathematical models have particular value in their ability to assess uncertainty in clinical care. Examples include parameters determined in …. (shrink)

A family had a child in large part to use its marrow in the hopes of saving the life of an older child afflicted with leukaemia. Public response from medical ethicists was negative. This paper argues that what the family did was not clearly wrong and that the ethicists should not have made public pronouncements calling the morals of the family into question.