Abstract：
:The exact contribution of the sirtuin family of NAD+-dependent histone deacetylases to longevity in metazoans is, at present, not completely understood but nonetheless regarded as significant. Despite the rapidly accreting evidence solidifying the role of NAD+-dependent histone deacetylase activity in longevity-promoting experimental interventions, the utility of histone-deacetylase inhibitors in the management of a diverse group of oncologic conditions draws question to the notion of universally beneficial effects of experimental interventions designed to promote deacetylase activity. The recent determination that overexpression of any one of the seven human sirtuin deacetylases fails to extend replicative lifespan in differentiated human cells calls attention to the possibility of unforeseen complexity in the determinants of human lifespan. Furthermore, inhibitors of histone deacetylases have been shown to actually increase lifespan in Drosophila. Delineation of the disparate effects of histone-deacetylase activity in stem cells, progenitor cells, and fully differentiated cells may confirm initial findings suggesting that histone-deacetylase inhibitors push malignant cells towards terminal differentiation, while simultaneously exerting a proliferative and differentiating effect on normal stem cells. This effect may ultimately exert an accelerating influence on the aging of the stem cell population and consequently produce detrimental alterations in stem and progenitor cell populations that compromise organismal-level longevity in mammals, in contrast to findings in Drosophila. This opens the possibility of a new side effect to a widely used chemotherapeutic, as well as the possibility of the generation of novel experimental systems that could leverage the putatively pro-aging influence of histone-deacetylase inhibitors to explore aging.
journal_name
Med Hypothesesjournal_title
Medical hypothesesauthors
Tapia PCdoi
10.1016/j.mehy.2005.08.032keywords:
subject
Has Abstractpub_date
2006-01-01 00:00:00pages
332-6issue
2eissn
0306-9877issn
1532-2777pii
S0306-9877(05)00437-8journal_volume
66pub_type
杂志文章abstract：:A high incidence of sudden unexplained nocturnal deaths has been reported among young Asian males. These deaths are known as Pokkuri in Japan, Bangungut in the Philippines and Sudden Unexplained Nocturnal Death in the United States. Post mortem analysis has demonstrated cardiac conduction defects in many of the victim...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(88)90071-0
更新日期：1988-06-01 00:00:00
abstract：:Increased level of oxalates in urine and plasma can be attributed to endogenous overproduction, increased ingestion or excessive intestinal absorption. When a supersaturation status is reached, oxalates combine with calcium and crystallize to form 80% of the urinary stones. Several cardiovascular diseases such as coro...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2020.109570
更新日期：2020-04-01 00:00:00
abstract：:Novel coronavirus (NCoV-19), also known as SARS CoV-2, is a pathogen causing an emerging infection that rapidly increases in incidence and geographic range, is associated with the ever-increasing morbidity and mortality rates, and shows sever economic impact worldwide. The WHO declares the NCoV-19 infection disease (C...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2020.109790
更新日期：2020-04-24 00:00:00
abstract：:The incidence rate of cutaneous melanoma has been increasing faster than that of any other cancer in white-skinned populations over the past decades. The main risk factors for melanoma (i.e. exposure to sunlight, naevus count, phototype, and family history of melanoma) may not wholly explain the epidemiological trends...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2010.03.010
更新日期：2010-09-01 00:00:00
abstract：:The etiologic basis of urinary tract anomalies and dysfunctional voiding largely remain unknown. However, the travel of urine from renal pelvis into the amniotic cavity under the pressures exerted by amniotic fluid satisfactorily explains the etiologic basis. Amniotic pressure is affected by the changes in maternal in...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1054/mehy.1998.0819
更新日期：2000-01-01 00:00:00
abstract：:Intrinsic radio-sensitivity is the determinant of differential response of tumours to low LET ionising radiations. The probabilistic DNA fibril both model shows intrinsic radio-sensitivity factor [I] as function of nuclear diameter (Nd) and intra cellular hydrogen ion concentration [H+]. Linking probabilities of letha...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2013.09.031
更新日期：2013-12-01 00:00:00
abstract：:The goal in the treatment of osteonecrosis of the femoral head is to preserve, not replace, the femoral head. Although many methods have been proposed, none has proved completely satisfactory. Cellular mediators as a supplement to bone grafting and decompression is an attractive approach to this problem because it com...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2006.08.024
更新日期：2007-01-01 00:00:00
abstract：:A new approach to antiviral therapy is proposed, taking advantage of the recently investigated innervation of immune tissues by the sympathetic nervous system, which establishes a functional connection between the nervous and the immune system, where the sympathetic nervous system exerts a varying tonic inhibitory inf...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(95)90097-7
更新日期：1995-10-01 00:00:00
abstract：:Although many risk factors influence atherogenesis, LDL appears to play a primary role in this process. In prospective epidemiology, coronary risk increases as LDL cholesterol increases, throughout the entire range of concentrations encountered in healthy humans. Coronary risk is minimal in individuals and populations...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2003.12.051
更新日期：2005-01-01 00:00:00
abstract：:The largely empirical dopamine theory has limited value in clarifying the pathogenesis of schizophrenia, due to its inability to explain consistent imaging findings, such as cortical grey matter loss, reduced frontal and thalamic activity, and, reduced D1 receptor load. Furthermore, the most effective drug for treatin...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2005.06.022
更新日期：2005-01-01 00:00:00
abstract：:Computer algorithms can only produce seemingly random or pseudorandom numbers whereas certain natural phenomena, such as the decay of radioactive particles, can be utilized to produce truly random numbers. In this study, the ability of humans to generate random numbers was tested in healthy adults. Subjects were simpl...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2005.02.019
更新日期：2005-01-01 00:00:00
abstract：:Except for a few diseases of molecular mimicry such as rheumatic fever, post-streptococcal glomerulonephritis in children, and gluten-sensitive enteropathy, the cause of autoimmune diseases is unknown. Most autoimmune diseases are remitting-relapsing and the pathophysiology of either the initial attack or subsequent r...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2013.01.015
更新日期：2013-05-01 00:00:00
abstract：:Chronic idiopathic axonal polyneuropathy (CIAP) is referred to as axonal neuropathy after an adequate workup fails to determine a cause. A subgroup of patients with CIAP has impaired glucose tolerance (IGT). These patients have been considered by some investigators to have a neuropathy as a result of IGT and/or metabo...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2010.12.012
更新日期：2011-04-01 00:00:00
abstract：:Radiotherapy (RT) has been established to improve both local control as well as overall survival rates in breast cancer. However, RT especially in left-sided breast cancer also irradiates a portion of the heart. Radiation associated toxicity to the heart assumes significance because of improval in survival of breast c...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2011.12.009
更新日期：2012-03-01 00:00:00
abstract：:The pancreatic leakage is a lethal postoperative complication to the patients after duodenopancreatectomy for carcinoma of head of pancreas. However, we found that the patients who survived this lethal postoperative complication could potentially acquire a longer survival time comparing with those without postoperativ...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2009.02.024
更新日期：2009-08-01 00:00:00
abstract：:Cardiac chambers have afferent connections to the brainstem and to the spinal cord. Vagal afferents mediate depressor responses and become activated by volume expansion, increased myocardial contractility and atrial natriuretic factor. Sympathetic afferents, on the contrary, are activated by metabolic mediators, myoca...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1054/mehy.1999.0029
更新日期：2000-02-01 00:00:00
abstract：:Timely recanalization of infarct related artery along with effective myocardial cell reperfusion represents a major challenge in the management of STEMI. The reperfusion of coronary arteries can induce further cardiomyocyte death by generating oxidative stress, which itself can mediate myocardial damage through a numb...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2017.03.010
更新日期：2017-05-01 00:00:00
abstract：:HLA-G is a nonclassical HLA immunotolerogenic molecule expressed in different human cell types. Successful embryo implantation is a consequence of information exchange between the uterus and the blastocyst. It is widely accepted that HLA-G expression by the fetus promotes the establishment of several mechanisms that, ...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2017.03.030
更新日期：2017-05-01 00:00:00
abstract：:Transient period represents the time window between the exposure and response to the given stimuli inflicting the stress on the host. However, this time window is unlikely to engage in variety of signaling to culminate drastic impact on the host cell rather it is evolutionary in its sense implying a slow process. But ...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2003.04.001
更新日期：2004-01-01 00:00:00
abstract：:Prepulse inhibition (PPI) of acoustic startle reflex is a measure of sensorimotor gating that may reflect the biological processes underlying gaiting impairments in schizophrenia. Although PPI is clinically useful, why PPI is inhibited in schizophrenia is largely unknown. Prepulse inhibition is mediated by M2-like mus...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2020.109901
更新日期：2020-10-01 00:00:00
abstract：:A role for lipopolysaccharides (endotoxins, LPS) in 7 the pathogenesis of Reye's syndrome (RS) has previously been suggested. Impairment of hepatic LPS clearance can lead to systemic endotoxemia as previous studies by this and other laboratories have suggested for several hepatic disorders including RS. Systemic LPS m...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(92)90115-s
更新日期：1992-11-01 00:00:00
abstract：:In endemic pemphigus foliaceus (EPF) or "fogo selvagem" the epidemiological evidence shows that all the described outbreaks occur on the banks of rivers where there is mercury contamination from alluvium gold mining and deforestation. Pathophysiological evidence shows a similarity to pemphigus induced by sulphydryl (S...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2011.09.041
更新日期：2012-01-01 00:00:00
abstract：:Atrial fibrillation (Af) is the most common disorder of cardiac rhythm and is responsible for substantial morbidity and mortality in the general population. A recent community-based observational study revealed that diabetes and hypertension were associated with the development of Af. Since there is no definite eviden...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2005.07.018
更新日期：2006-01-01 00:00:00
abstract：:Genetic and environmental influences are both known to be causal factors in the development and maintenance of obesity. Stress related chronic stimulation of the hypothalamic-pituitary-adrenal (HPA) axis and resulting increased glucocorticoid exposure are known to be important pathophysiological mechanisms in the deve...
journal_title：Medical hypotheses
pub_type： 杂志文章,评审
doi：10.1016/j.mehy.2010.10.049
更新日期：2011-03-01 00:00:00
abstract：:We describe here a new technique for analyzing human growth curves using a first order kinetic representation. Plotting in ([h infinity-ht)/h infinity] vs time (where h infinity and ht represent the final and instantaneous heights) transforms growth curves into 3 linear phases and 2 interphases. These growth parameter...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(85)90073-8
更新日期：1985-02-01 00:00:00
abstract：:High level contamination by natural and industrial sources of the alkali earth metal, barium (Ba) has been identified in the ecosystems/workplaces that are associated with high incidence clustering of multiple sclerosis (MS) and other neurodegenerative diseases such as the transmissible spongiform encephalopathies (TS...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2003.12.034
更新日期：2004-01-01 00:00:00
abstract：:The internal thoracic arteries (ITAs) are a source of "noncoronary collateral circulation" (NCCC), or "noncoronary collateral blood flow" (NCCBF). The hypothesis herein is that enhancement of NCCC may represent an alternative means of myocardial blood supply: (1) Ligature of the ITAs creates a local hypertensive statu...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2009.08.027
更新日期：2010-01-01 00:00:00
abstract：:The Davson-Danielli model of the cell membrane accounted for nearly all the space within it by suggesting that it was composed of structural proteins and lipids; this would leave virtually no space for the large number of enzymes, carriers, antigens, antibodies, and receptors for hormones, transmitters, drugs and toxi...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(88)90100-4
更新日期：1988-07-01 00:00:00
abstract：:'Electrohypersensitivity' is often explained as a psychological syndrome. Our modern environment contains a lot of different substances and some of them are toxic. Mycotoxins are types of toxins that are biologically very active and that affect living organisms. Mycotoxins and fungi capable of producing toxins have be...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1054/mehy.1999.1045
更新日期：2000-09-01 00:00:00
abstract：:Autism is a complex and heterogeneous neurodevelopmental disorder of unknown etiology but very likely resulting from both genetic and environmental factors. Recent estimates suggest that it affects 1 in 100-150 individuals in the US. Oxidative stress, inflammation and mitochondrial dysfunction have all been suggested ...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2012.01.032
更新日期：2012-04-01 00:00:00
