Abstract:
:The mechanism by which polyglutamine expansions in several proteins lead to neurodegenerative disorders remains largely unknown. The biochemical properties of polyglutamine repeats suggest one possible explanation; endolytic cleavage at a glutaminyl-glutaminyl bond followed by pyroglutamate formation may contribute to the pathogenesis through augmenting the catabolic stability, hydrophobicity, amyloidogenicity, and neurotoxicity of the polyglutaminyl proteins. The hypothesis points out novel therapeutic strategies to delay disease onset in genetically diagnosed presymptomatic patients.
journal_name
Med Hypothesesjournal_title
Medical hypothesesauthors
Saido TCdoi
10.1054/mehy.1999.0866keywords:
subject
Has Abstractpub_date
2000-03-01 00:00:00pages
427-9issue
3eissn
0306-9877issn
1532-2777pii
S0306-9877(99)90866-6journal_volume
54pub_type
杂志文章abstract::The exact nature of the mechanism that triggers initiation of chromosome replication in the best understood of all organisms, Escherichia coli, remains mysterious. Here, I suggest that this mechanism evolved in response to the problems that arise if chromosome replication does not occur. E. coli is now known to be hig...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2011.02.002
更新日期:2011-05-01 00:00:00
abstract::The author reviews the criticism aimed at medical education and suggests that its shortcomings could be corrected by modifying the curriculum so that irrelevant material is eliminated and replaced in part with the humanities. ...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/0306-9877(80)90104-8
更新日期:1980-05-01 00:00:00
abstract::Space adaptation syndrome (SAS) incapacitates about 50% of the astronauts with symptoms of headache, malaise, vomiting, vertigo, etc. A hypothesis that SAS is caused by elevated intracranial pressure secondary to the cephalad fluid shift in zero G is proposed. A mechanism of how the cephalad fluid shift could cause el...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/0306-9877(90)90108-q
更新日期:1990-08-01 00:00:00
abstract::Several studies have described unusually high incidence of vascular thrombosis in coronavirus disease-2019 (COVID-19) patients. Pathogenesis of the vascular thrombosis in COVID-19 is least understood for now and presents a challenge to the treating physicians. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2020.110320
更新日期:2020-12-01 00:00:00
abstract::We describe a new term: glutamate-based depression (GBD). GBD is defined as a chronic depressive illness associated with environmental stress and diseases associated with altered glutamate neurotransmission. We hypothesize that glutamate-induced over-activation of extrasynaptic NMDA receptors in the subgenual cingulat...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2012.02.009
更新日期:2012-05-01 00:00:00
abstract::Homocysteine is a sulfur-containing amino acid produced by the breakdown of methionine. Plasma homocysteine levels can be elevated due to a variety of genetic and nutritional factors. Poor nutrition from diets low in folate and vitamin B12 can lead to hyperhomocysteinemia. Mildly elevated levels of homocysteine have b...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1054/mehy.2000.1116
更新日期:2001-01-01 00:00:00
abstract::This thesis explores the activation of chemicals in metabolic systems from the viewpoint that this activation is under the control of elements of the space-sea in which the chemicals are immersed. Themselves inert, the chemicals are theorised to exploit a force or action issuing from space (fluctuation) and characteri...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1054/mehy.2001.1298
更新日期:2001-07-01 00:00:00
abstract::By influencing fetal brain development pregnancy may be prolonged beyond term for an unknown time period. In late gestation the mother animal (host) is nephrectomized. The urine of the fetus (transplant) is guided to the outside so that the fetal kidneys excrete the host's urinary secretory substances and eventually h...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/0306-9877(82)90078-0
更新日期:1982-10-01 00:00:00
abstract::Information about the etiology of pressure sores has been contradictory and is inconsistent with the idea that pressure sore formation is due extensively to depriving a tissue region of blood. Based on these observations and on studies done in the cooperating laboratories, an hypothesis has been formulated that integr...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/0306-9877(83)90067-1
更新日期:1983-06-01 00:00:00
abstract::Recently, a mini-review was published in the Medical Hypotheses journal by Usul Afsar entitled 2019-nCoV-SARS-CoV-2 (COVID-19) infection: Cruciality of Furin and relevance with cancer. Previous studies have pointed out that disruption of the proteolytic cleavage of proteins can promote infectious and non-infectious di...
journal_title:Medical hypotheses
pub_type: 信件
doi:10.1016/j.mehy.2020.109893
更新日期:2020-10-01 00:00:00
abstract::With spinal anesthesia the level of surgical analgesia is mostly reported without reference to the neuroanatomic map of spinal nerves. The classical maps are variably and inconsistently reported in many textbooks. Because of the differences between the classical maps of Keegan and Garrett and of Foerster, and also bec...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/s0306-9877(97)90116-x
更新日期:1997-06-01 00:00:00
abstract::Triggering receptor expressed on myeloid cells-1 (TREM-1) is a recently identified cell surface receptor that is expressed mainly on monocytes and neutrophils, and plays an important role as an amplifier of inflammatory response in acute and chronic inflammatory conditions. Recent studies suggested that TREM-1 contrib...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2011.10.042
更新日期:2012-02-01 00:00:00
abstract::It is proposed here that the initial events in gastric carcinogenesis occur at the junction of the oxyntic and antral mucosae. Intestinal metaplasia represents an adaptive counter-response to early neoplastic change at this site. Chronic gastric ulceration may arise due to the elimination of overtly dedifferentiated c...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/0306-9877(91)90229-r
更新日期:1991-07-01 00:00:00
abstract::The activity of the lithium ion against DNA type viruses is explained by its competition with magnesium ions. Magnesium acts as the cofactor of the enzymes responsible for the replicative building of viral proteins and nucleosides. When lithium replaces magnesium, it appears to render the polymerase enzymes impotent. ...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/0306-9877(87)90152-6
更新日期:1987-06-01 00:00:00
abstract::COVID-19 due to the SARS-CoV-2 infection is a multi-systemic immune syndrome affecting mainly the lungs, oropharyngeal region, and other vascular endothelial beds. There are tremendous ongoing efforts for the aim of developing drugs against the COVID-19 syndrome-associated inflammation. However, currently no specific ...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2020.110150
更新日期:2020-10-01 00:00:00
abstract::Alzheimer's disease is a debilitating age-related disorder characterized by distinct pathological hallmarks, such as progressive memory loss and cognitive impairment. During the last few years, several cellular signaling pathways have been associated with the pathogenesis of Alzheimer's disease, such as Notch, mTOR an...
journal_title:Medical hypotheses
pub_type: 杂志文章,评审
doi:10.1016/j.mehy.2015.01.026
更新日期:2015-04-01 00:00:00
abstract::In Burkitt's lymphoma, dental structures may provide the route for Epstein-Barr virus (EBV) in saliva to penetrate the jaws, thereby promoting tumor formation. In children, EBV could enter tooth sockets exposed following deciduous tooth loss and thereby contact jaw marrow lymphocytes stimulating neoplastic transformat...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/0306-9877(83)90105-6
更新日期:1983-12-01 00:00:00
abstract::Recent findings indicate a principal role for Hepcidin in iron homeostasis. Hepcidin is also thought to play a vital role in the pathogenic mechanism of anaemia in patients with inflammation or chronic disease. Under normal conditions influx and efflux of iron from duodenal enterocytes is regulated by Ferroportin. Fer...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2007.10.007
更新日期:2008-01-01 00:00:00
abstract::Breast cancer associated with pregnancy is defined as the one in which the diagnosis is made in a pregnancy or within one year of delivery. Breast cancer is the second most common malignancy during pregnancy and it is generally considered to have a worse prognosis than the one that is not associated with pregnancy. Th...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2006.05.072
更新日期:2007-01-01 00:00:00
abstract::The pathogenesis of seasonal affective disorder (SAD) has been attributed to abnormal melatonin metabolism. Perorally administered psoralens increase the daytime levels of melatonin via the competitive inhibition of hepatic melatonin metabolism. Some findings among SAD patients are parallel to those observed after the...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/s0306-9877(98)90267-5
更新日期:1998-06-01 00:00:00
abstract::While cigarette smoking is recognized as an important risk factor in human oral cancers, the effect of water pipe smoking (WPS) on these cancers is not known. WPS is very common in the young adult population, especially in the Middle East, and has been associated with several respiratory problems. However, to date, th...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2009.10.013
更新日期:2010-03-01 00:00:00
abstract::Long pentraxin 3 (PTX3) is a recently discovered multimeric inflammatory mediator that is structurally linked to short pentraxins, such as C-reactive protein (CRP) and serum amyloid P component. PTX3 is produced by a variety of tissues and cells, including vascular endothelial cells and macrophages. Because of its ext...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2012.05.011
更新日期:2012-09-01 00:00:00
abstract::Bony abnormalities are common findings in cases of neurofibromatosis 1. We might hypothesize that neurofibromin, the protein encoded by the neurofibromatosis 1 gene, plays important roles in bone development. Loss of function of oligodendrocyte-myelin glycoprotein gene and increased activity of ras p21 might increase ...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/s0306-9877(02)00225-6
更新日期:2003-04-01 00:00:00
abstract::Although membrane sphingomyelin (SPH) serves as the precursor for many signaling molecules, its presence in large amounts, and its specific localization in the outer monolayer of the plasma membrane suggest that it may have a cytoprotective function. We propose that SPH helps maintain the integrity of the plasma membr...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1054/mehy.2001.1336
更新日期:2001-08-01 00:00:00
abstract::There are different theories and hypotheses related to the aetiology of depression. The interaction between brain 5-HT level and the activity of its autoreceptors plays a role in mood changes and depression. In major depression, activation of the inflammatory response system (IRS) and, increased concentrations of proi...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/s0306-9877(03)00207-x
更新日期:2003-11-01 00:00:00
abstract::Alcoholism is a major and world-wide health problem. A characteristic pattern of congenital defects, known as the fetal alcohol syndrome, has been detected in the offspring of mothers who are chronic alcoholics. The mechanism underlying the teratogenic effects of ethanol is not known. An important hypothesis is that e...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/0306-9877(91)90185-2
更新日期:1991-02-01 00:00:00
abstract::Trypanosomiasis (whether African sleeping sickness, or American Chaga's disease) is caused by an infection with a protozoan parasite, i.e. the trypanosome. This carries fatal sequences in the untreated host. Currently available chemotherapeutic drugs (some of which cure by involving reactive oxygen species (ROS] are n...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/0306-9877(91)90142-l
更新日期:1991-11-01 00:00:00
abstract::This paper outlines a method of demonstrating hepatitis B virus (HBV)-related transcriptional activity based on the random amplification of cDNA ends (RACE) protocol. Following RNA extraction from the appropriate tissue, cDNA is synthesized using a long oligo d(T) based primer containing unique 5' oligonucleotide sequ...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/0306-9877(95)90056-x
更新日期:1995-08-01 00:00:00
abstract::It is sometimes asserted that UK science is thriving, at other times that it has declined. We suggest that both assertions are partly true because the UK is thriving with respect to the volume of 'normal' science production but at the same time declining in the highest level of 'revolutionary' science. Revolutionary s...
journal_title:Medical hypotheses
pub_type: 社论
doi:10.1016/j.mehy.2007.12.004
更新日期:2008-01-01 00:00:00
abstract::Thrombotic thrombocytopenic purpura (TTP) is a severe, occlusive, thrombotic microangiopathy characterized by a systemic platelet aggregation, organ ischemia, profound thrombocytopenia and erythrocyte fragmentation. Recent observations have documented that a deficiency of a von Willebrand factor (VWF)-cleaving proteas...
journal_title:Medical hypotheses
pub_type: 临床试验,杂志文章
doi:10.1016/j.mehy.2005.06.015
更新日期:2005-01-01 00:00:00