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1.
Sci Eng Ethics ; 25(5): 1409-1423, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30357560

RESUMO

The bioethical principle of autonomy is problematic regarding the future of the embryo who lacks the ability to self-advocate but will develop this defining human capacity in time. Recent experiments explore the use of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 for germline engineering in the embryo, which alters future generations. The embryo's inability to express an autonomous decision is an obvious bioethical challenge of germline engineering. The philosopher Joel Feinberg acknowledged that autonomy is developing in children. He advocated that to reserve this future autonomy, parents should be guided to make ethical decisions that provide children with open futures. Here, Feinberg's 1980 open future theory is extended to the human embryo in the context of CRISPR germline engineering. Although the embryo does not possess the autonomous decision-making capacity at the time of germline engineering, the parental decision to permanently change the unique genetic fabric of the embryo and subsequent generations disregards future autonomy. Therefore, germline engineering in many instances is objectionable considering Feinberg's open future theory.


Assuntos
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Desenvolvimento Embrionário , Teoria Ética , Engenharia Genética/ética , Engenharia Genética/tendências , Células Germinativas , Autonomia Pessoal , Tomada de Decisões/ética , Eticistas , Feminino , Engenharia Genética/legislação & jurisprudência , História do Século XX , Humanos , Masculino , Pais , Pessoalidade
3.
Rambam Maimonides Med J ; 14(4)2023 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-37917864

RESUMO

Xenotransplantation represents a viable solution to meet the great need to provide organ donors at a time when there are not enough human organ donors. A lot of clinical studies have focused on using genetically engineered pigs as the prime source for organ transplantation. However, several religions, such as Judaism and Islam, have restrictions on the use of pigs for food or in business. In this article, we review the Jewish perspectives on xenotransplantation. Overall, the preservation of human life trumps most of the potential religious concerns associated with xenotransplantation. However, there are religious nuances related to xenotransplantation that are highlighted here, and that must be addressed by rabbinical scholars.

4.
Rambam Maimonides Med J ; 13(4)2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36394501

RESUMO

Clustered regularly interspaced short palindromic repeats (CRISPR) gene editing is an innovative and potentially game-changing biotechnology that can potentially reverse DNA mutations in a tissue-specific manner. In addition, CRISPR is being targeted for xenotransplantation, for increasing human longevity, in animal breeding, and in plant science. However, there are many ethical challenges that emerge from CRISPR technology. This article discusses several positions that relate to these ethical challenges from a Jewish legal perspective. In addition, we present several other applications of CRISPR technology that lack a defined Jewish legal precedent and require rabbinical scholars to address and resolve them in the future.

5.
Nat Med ; 9(4): 453-7, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12612547

RESUMO

Alzheimer disease (AD) is a progressive neurodegenerative disorder characterized by excessive deposition of amyloid-beta (Abeta) peptides in the brain. One of the earliest neuropathological changes in AD is the accumulation of astrocytes at sites of Abeta deposition, but the cause or significance of this cellular response is unclear. Here we show that cultured adult mouse astrocytes migrate in response to monocyte chemoattractant protein-1 (MCP-1), a chemokine present in AD lesions, and cease migration upon interaction with immobilized Abeta(1-42). We also show that astrocytes bind and degrade Abeta(1-42). Astrocytes plated on Abeta-laden brain sections from a mouse model of AD associate with the Abeta deposits and reduce overall Abeta levels in these sections. Our results suggest a novel mechanism for the accumulation of astrocytes around Abeta deposits, indicate a direct role for astrocytes in degradation of Abeta and implicate deficits in astroglial clearance of Abeta in the pathogenesis of AD. Treatments that increase removal of Abeta by astrocytes may therefore be a critical mechanism to reduce the neurodegeneration associated with AD.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Astrócitos/metabolismo , Fragmentos de Peptídeos/metabolismo , Animais , Astrócitos/imunologia , Movimento Celular , Quimiocina CCL2/farmacologia , Camundongos
6.
J Exp Med ; 200(5): 613-22, 2004 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-15353554

RESUMO

We showed previously that the competition between bacterial killing by neutrophils and bacterial growth in stirred serum-containing suspensions could be modeled as the competition between a first-order reaction (bacterial growth) and a second-order reaction (bacterial killing by neutrophils). The model provided a useful parameter, the critical neutrophil concentration (CNC), below which bacterial concentration increased and above which it decreased, independent of the initial bacterial concentration. We report here that this model applies to neutrophil killing of bacteria in three-dimensional fibrin matrices and in rabbit dermis. We measured killing of 10(3)-10(8) colony forming units/ml Staphylococcus epidermidis by 10(5)-10(8) human neutrophils/ml in fibrin gels. The CNC was approximately 4 x 10(6) neutrophils/ml gel in the presence of normal serum and approximately 1.6 x 10(7) neutrophils/ml gel in the presence of C5-deficient serum. Application of our model to published data of others on killing of approximately 5 x 10(7) to 2 x 10(8) E. coli/ml rabbit dermis yielded CNCs from approximately 4 x 10(6) to approximately 8 x 10(6) neutrophils/ml dermis. Thus, in disparate tissues and tissuelike environments, our model fits the kinetics of bacterial killing and gives similar lower limits (CNCs) to the neutrophil concentration required to control bacterial growth.


Assuntos
Neutrófilos/microbiologia , Neutrófilos/patologia , Animais , Divisão Celular , Meios de Cultura/metabolismo , Escherichia coli/metabolismo , Fibrina/química , Fibrina/metabolismo , Humanos , Cinética , Microscopia Confocal , Neutrófilos/metabolismo , Coelhos , Pele/microbiologia , Staphylococcus epidermidis/metabolismo , Fatores de Tempo
9.
Kennedy Inst Ethics J ; 18(4): 347-67, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19143409

RESUMO

The potential use of stem cells in the treatment of a variety of human diseases has been a major driving force for embryonic stem cell research. Another productive area of research has been the use of human stem cells to reconstitute human organ systems in animals in an attempt to create new animal models for human diseases. However, the possibility of transplanting human embryonic brain cells or precursor brain cells into an animal fetus presents numerous ethical challenges. This paper examines, from a Jewish perspective on human dignity, several bioethical concerns related to the reconstitution of animal brains with human neurons.


Assuntos
Transplante de Tecido Encefálico , Encéfalo/citologia , Pesquisas com Embriões/ética , Células-Tronco Embrionárias , Características Humanas , Direitos Humanos , Judaísmo , Animais , Quimera , Desumanização , Modelos Animais de Doenças , Ética em Pesquisa , Humanos , Especificidade da Espécie
10.
Rambam Maimonides Med J ; 9(1)2018 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-29406847

RESUMO

A great deal of biomedical research focuses on new biotechnologies such as gene editing, stem cell biology, and reproductive medicine, which have created a scientific revolution. While the potential medical benefits of this research may be far-reaching, ethical issues related to non-medical applications of these technologies are demanding. We analyze, from a Jewish legal perspective, some of the ethical conundrums that society faces in pushing the outer limits in researching these new biotechnologies.

12.
J Leukoc Biol ; 71(5): 798-806, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-11994504

RESUMO

fMLP- or TNF-alpha-stimulated neutrophils produced H(2)O(2) when they adhered to fibrinogen-coated surfaces but not when they adhered to collagen I-, collagen IV-, or Matrigel-coated surfaces. In contrast, LTB4- or IL-8-stimulated neutrophils did not produce H(2)O(2) when they adhered to any of these surfaces. fMLP and TNF-alpha were much more potent than LTB4 and IL-8 in stimulating neutrophils to up-regulate and to activate their alpha(M)beta(2) integrins, as measured by the binding of specific monoclonal antibodies. Pretreatment of neutrophils with pertussis toxin completely blocked their production of H(2)O(2) on fibrinogen-coated surfaces in response to fMLP and their migration through Matrigel in response to fMLP, LTB4, and IL-8. These data show that although the fMLP, LTB4, and IL-8 receptors are coupled to pertussis toxin-sensitive Galpha proteins, they signal neutrophils to initiate qualitatively different effector functions. We propose that the qualitative differences in effector functions signaled by different chemoattractants reflect qualitative differences in using G-protein beta and/or gamma subunits or other factors by their cognate receptors.


Assuntos
Fatores Quimiotáticos/farmacologia , Quimiotaxia de Leucócito , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Neutrófilos/imunologia , Receptores Imunológicos/metabolismo , Antígenos CD18/fisiologia , Adesão Celular , Células Cultivadas , Fatores Quimiotáticos/antagonistas & inibidores , Quimiotaxia de Leucócito/efeitos dos fármacos , Proteínas da Matriz Extracelular/farmacologia , Proteínas Heterotriméricas de Ligação ao GTP/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Cinética , Neutrófilos/efeitos dos fármacos , Toxina Pertussis , Transdução de Sinais , Fatores de Virulência de Bordetella/farmacologia
13.
Curr Top Behav Neurosci ; 22: 237-70, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25293443

RESUMO

The motor symptoms of Parkinson's disease are due to the progressive degeneration of dopaminergic neurons in the substantia nigra. Multiple neuroinflammatory processes are exacerbated in Parkinson's disease, including glial-mediated reactions, increased expression of proinflammatory substances, and lymphocytic infiltration, particularly in the substantia nigra. Neuroinflammation is also implicated in the neurodegeneration and consequent behavioral symptoms of many Parkinson's disease animal models, although it is not clear whether these features emulate pathogenic steps in the genuine disorder or if some inflammatory features provide protective stress responses. Here, we compare and summarize findings on neuroinflammatory responses and effects on behavior in a wide range of toxin-based, inflammatory and genetic Parkinson's disease animal models.


Assuntos
Modelos Animais de Doenças , Inflamação , Doença de Parkinson , Animais , Inflamação/imunologia , Inflamação/patologia , Inflamação/fisiopatologia , Doença de Parkinson/imunologia , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia
14.
Rambam Maimonides Med J ; 6(3)2015 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-26241230

RESUMO

The transition of new biotechnologies into clinical trials is a critical step in approving a new drug or therapy in health care. Ethically recruiting appropriate volunteers for these clinical trials can be a challenging task for both the pharmaceutical companies and the US Food and Drug Administration. In this paper we analyze the Jewish halachic perspectives of volunteering for clinical trials by focusing on an innovative technology in reproductive medicine, mitochondrial replacement therapy. The halachic perspective encourages individuals to volunteer for such clinical trials under the ethical principles of beneficence and social responsibility, when animal studies have shown that health risks are minimal.

15.
J Clin Invest ; 125(2): 539-50, 2015 02.
Artigo em Inglês | MEDLINE | ID: mdl-25562324

RESUMO

In contrast to microbially triggered inflammation, mechanisms promoting sterile inflammation remain poorly understood. Damage-associated molecular patterns (DAMPs) are considered key inducers of sterile inflammation following cell death, but the relative contribution of specific DAMPs, including high-mobility group box 1 (HMGB1), is ill defined. Due to the postnatal lethality of Hmgb1-knockout mice, the role of HMGB1 in sterile inflammation and disease processes in vivo remains controversial. Here, using conditional ablation strategies, we have demonstrated that epithelial, but not bone marrow-derived, HMGB1 is required for sterile inflammation following injury. Epithelial HMGB1, through its receptor RAGE, triggered recruitment of neutrophils, but not macrophages, toward necrosis. In clinically relevant models of necrosis, HMGB1/RAGE-induced neutrophil recruitment mediated subsequent amplification of injury, depending on the presence of neutrophil elastase. Notably, hepatocyte-specific HMGB1 ablation resulted in 100% survival following lethal acetaminophen intoxication. In contrast to necrosis, HMGB1 ablation did not alter inflammation or mortality in response to TNF- or FAS-mediated apoptosis. In LPS-induced shock, in which HMGB1 was considered a key mediator, HMGB1 ablation did not ameliorate inflammation or lethality, despite efficient reduction of HMGB1 serum levels. Our study establishes HMGB1 as a bona fide and targetable DAMP that selectively triggers a neutrophil-mediated injury amplification loop in the setting of necrosis.


Assuntos
Proteína HMGB1/metabolismo , Elastase de Leucócito/metabolismo , Infiltração de Neutrófilos , Neutrófilos/metabolismo , Receptores Imunológicos/metabolismo , Acetaminofen/efeitos adversos , Acetaminofen/farmacologia , Analgésicos não Narcóticos/efeitos adversos , Analgésicos não Narcóticos/farmacologia , Animais , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Proteína HMGB1/genética , Hepatócitos/metabolismo , Hepatócitos/patologia , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Elastase de Leucócito/genética , Lipopolissacarídeos/toxicidade , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Camundongos Knockout , Necrose/induzido quimicamente , Necrose/genética , Necrose/metabolismo , Necrose/patologia , Neutrófilos/patologia , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos/genética , Choque Séptico/induzido quimicamente , Choque Séptico/genética , Choque Séptico/metabolismo , Choque Séptico/patologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Receptor fas/genética , Receptor fas/metabolismo
18.
Kennedy Inst Ethics J ; 12(4): 343-50, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12645611

RESUMO

Research in genomics, human cloning, and transgenic technology has challenged bioethicists and scientists to rethink the definition of human beings as a species. For example, should the definition incorporate a genetic criterion and how does the capacity to genetically engineer human beings affect the definition of our species? In considering these contemporary bioethical dilemmas, we revisit an ancient source, the Talmud, and highlight how it provides specific biological, cultural, and genetic criteria to define the human species.


Assuntos
Engenharia Genética/ética , Características Humanas , Judaísmo , Animais , Animais Geneticamente Modificados/fisiologia , Clonagem de Organismos/ética , Haplorrinos/genética , Haplorrinos/fisiologia , Humanos , Religião e Ciência , Especificidade da Espécie
19.
J Microbiol Biol Educ ; 15(2): 186-90, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25574276

RESUMO

The field of assisted reproduction is renowned for its remarkable advances and constant pushing forward of research boundaries in an effort to offer innovative and effective methods for enhancing fertility. Accompanying these advances, however, are physiological, psychological, and bioethical consequences that must be considered. These concomitant advances and consequences make assisted reproduction an excellent educational paradigm for inculcating responsible conduct in both research and clinical practice. Ultimately, responsible conduct rests on the ethical researcher and clinician. Here, we present the as-yet unapproved, contentious assisted reproductive technology of mitochondrial replacement transfer (MRT) as an ideal educational platform to foster the responsible conduct of research by advancing dialogue among multi-disciplinary scholars, researchers, and students. Using a likely future case, we present the basic science, legal, and ethical considerations, and the pedagogical principles and strategies for using MRT as an effective educational paradigm. Society will benefit when the ethical issues inherent in creating children with three genetic parents as well as germline interference are discussed across multiple academic levels that include researchers, legal experts, bioethicists, and government-appointed commissions. Furthermore, undergraduate and graduate students should be included because they will likely determine the ethical fates of these biotechnologies. While emerging assisted reproduction technologies such as MRT are highly complex and will take years to be readily available for patients in need, now is the time to consider their scientific, legal, ethical, and cultural/religious implications for ensuring the responsible conduct of research.

20.
Front Neuroanat ; 8: 114, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25352786

RESUMO

Neuronal expression of major histocompatibility complex I (MHC-I) has been implicated in developmental synaptic plasticity and axonal regeneration in the central nervous system (CNS), but recent findings demonstrate that constitutive neuronal MHC-I can also be involved in neurodegenerative diseases by playing a neuroinflammtory role. Recent reports demonstrate its expression in vitro and in human postmortem samples and support a role in neurodegeneration involving proinflammatory cytokines, activated microglia and increased cytosolic oxidative stress. Major histocompatibility complex I may be important for both normal development and pathogenesis of some CNS diseases including Parkinson's.

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