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Allen D. Roses Margaret A. Pericak-Vance Ann M. Saunders Donald Schmechel Dmitry Goldgaber Warren Strittmatter 《Epilepsia》1994,35(S1):S20-S28
Summary: Strategies used in molecular genetics have changed modern neurology. The gene or genes responsible for several major neurologic diseases have now been identified using "reverse" or positional genetics. Unexpected new genetic mechanisms have been discovered in human neurologic diseases, including (a) identical mutations of the prion protein gene in Creutzfeldt-Jakob disease and fatal familial insomnia with the phenotypic expression directed by an accompanying polymorphism; (b) stable duplications of chromosome 17 in Charcot-Marie-Tooth disease (type 1 A) that involve many genes, only one of which appears to cause neuropathy; and (c) highly variable, dynamic mutations in myotonic dystrophy, fragile X syndrome, and Kennedy's syndrome that modulate variable expressivity in multiple tissues. There is growing recognition that neurologic diseases are often complex genetic diseases with multifactorial rather than simple modes of inheritance. For example, genetic association/linkage strategies have interacted with biochemistry and immunopathology studies to produce new insights into the disease mechanism of late-onset Alzheimer's disease. The role of apolipoprotein E in late-onset Alzheimer's disease is an example of how new analytical techniques of genetic disease can be applied to dissect multiple genes. Similar research strategies are suggested for the study of epilepsy as a complex disease. 相似文献
5.
Ischemic postconditioning: brief ischemia during reperfusion converts persistent ventricular fibrillation into regular rhythm 总被引:31,自引:0,他引:31
Michael Galagudza Dmitry Kurapeev Sarkis Minasian Guro Valen Jarle Vaage 《European journal of cardio-thoracic surgery》2004,25(6):406-1010
Objectives: Brief episodes of myocardial ischemia-reperfusion employed during reperfusion after a prolonged ischemic insult may attenuate the total ischemia-reperfusion injury. This phenomenon has been termed ischemic postconditioning. In the present study, we studied the possible effect of postconditioning on persistent reperfusion-induced ventricular fibrillation (VF) in the isolated rat heart model. Methods: Isolated Langendorff-perfused rat hearts (n=46) were subjected to 30 min of regional ischemia and reperfusion. The hearts with persistent VF (n=11) present after 15 min of reperfusion were then randomly assigned into one of the two groups: (1) control hearts (n=6), in which perfusion was continued without intervention; (2) postconditioned hearts (n=5) subjected to 2 min of global ischemia followed by reperfusion. Left ventricular pressures, heart rate, coronary flow, and electrogram were monitored throughout the experiment. Results: Conversion of VF into regular rhythm was observed in all hearts subjected to postconditioning. Regular beating was maintained by all postconditioned hearts during the subsequent reperfusion. None of the hearts in the control group had normal rhythm at the end of the experiment. At the end of reperfusion, the left ventricular developed pressure was lower in beating postconditioned hearts compared to the hearts that did not develop persistent VF. Conclusions: Ischemic postconditioning possesses strong antiarrhythmic effect against persistent reperfusion-induced tachyarrhythmias. Postconditioning may be an interesting, novel adjunct strategy to protect the heart. 相似文献
6.
P. A. Galenko-Yaróshevskii I. S. Chekman O. S. Medvedev V. I. Kondratyuk K. S. Vas'kov A. V. Uvarov S. E. Gumenyuk V. N. Kovalenko P. B. Popov V. L. Popkov 《Bulletin of experimental biology and medicine》1998,126(4):1017-1020
Sodium succinate improves the survival of a skin graft in mice, rats, and dogs normalizes histamine and serotonin concentrations
in the epidermis and blood, exhibits antitoxic activity, improves microcirculation in the skin, brain, heart, kidneys, and
testes without any appreciable effect on systemic arterial pressure, cardiac function, and liver blood flow in rats.
Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 10, pp. 420–424, October, 1998 相似文献
7.
Verbenko DA Pogoda TV Spitsyn VA Mikulich AI Bets LV Bebyakova NA Ivanov VP Abolmasov NN Pocheshkhova EA Balanovskaya EV Tarskaya LA Sorensen MV Limborska SA 《European journal of human genetics : EJHG》2003,11(6):444-451
Apolipoprotein B 3' (3' ApoB) minisatellite polymorphism was studied in healthy unrelated individuals from the Russian Federation and the Republic of Belarus, in 10 populations from five ethnic groups: Russians, Byelorussians, Adygeis, Kalmyks and Yakuts. The analysis was carried out using PCR and electrophoresis followed by silver staining. Overall, 25 alleles of the 3' ApoB minisatellite, ranging from 25 to 55 repeats, were detected. Heterozygosity indices were high and varied from 0.73 to 0.84. The distributions of alleles of this minisatellite in the Caucasoid populations (Russians, Byelorussians and Adygeis) had a bimodal character, whereas that for Mongoloid populations (Kalmyks and Yakuts) had a unimodal distribution. Nei's genetic distances between the populations studied and some reference populations of Europe and Asia were estimated. Despite their allele distribution homogeneity, different East Slavonic ethnic groups were clearly resolved by multidimensional analyses. The East Slavonic and Adygei populations revealed a high similarity with European Caucasoids. The Mongoloid populations (Kalmyks and Yakuts) were considerably different from those of the European Caucasoid populations, but were similar to other Asian Mongoloid populations. The results demonstrate the variability of 3' ApoB minisatellite polymorphism not only in distant populations but also, to a certain extent, in genetically relative ones. 相似文献
8.
Laura McGillis Nimish Mittal Daniel Santa Mina Joyce So Medha Soowamber Aliza Weinrib Leslie Soever Dmitry Rozenberg Louis Liu Yvonne Tse Joel Katz George S Charames Kieran Murphy Peter Vadas Maxwell P Slepian Scott Walsh Lindsay Wilson Arnon Adler Alyssa Franzese Laura Hussey Dayna‐Lynn Nevay Juan Guzman Hance Clarke 《American journal of medical genetics. Part A》2020,182(3):484-492
The new 2017 diagnostic criteria for hypermobile Ehlers–Danlos Syndrome (hEDS) provide a framework for diagnosing hEDS but are more stringent than the previous Villefranche criteria. Our clinical experience at the GoodHope EDS clinic was that the 2017 criteria left many highly symptomatic patients without a diagnosis of hEDS. We conducted a retrospective cohort study to confirm our clinic experience and assess the accuracy of the 2017 diagnostic criteria for hEDS in patients who had a previous hEDS diagnosis based on the Villefranche criteria. Our study found that 15% (n = 20 of 131) of patients with a prior diagnosis of hEDS met the 2017 diagnostic criteria, and many of the traits used to distinguish hEDS were not significantly more frequent in patients who met 2017 criteria versus those who did not. In both groups objective systemic manifestations were found less frequently than subjective systemic manifestations. Beighton score (BS) as assessed by primary care practitioner was found to be higher than assessment by EDS practitioner in 81% (n = 74 of 91) of cases. Generalized joint hypermobility was confirmed in only 46% (n = 51 of 111) of patients who had a previous diagnosis of hEDS. Higher BS did not correlate with increased number of systemic manifestations in our cohort. Common comorbidities of hEDS were found with similar frequency in those who met 2017 criteria and those who did not. Based on our cohort, the 2017 hEDS diagnostic criteria require refinement to improve its diagnostic accuracy. 相似文献
9.
The effect of extracellular pH (pHe 6.9–8.1) and intracellular pH (pHi 6.4–8.1) on the non-inactivating voltage-sensitive M-like potassium current (IKx) was studied in patch-clamped salamander rod photoreceptors. The midpoint of the IKx activation curve shifted by 6.6 mV per pHe unit, with acidification producing positive shifts and alkalinization producing negative shifts. The time constant of IKx activation shifted with pHe in a manner consistent with the shifts in the activation curve. Maximum conductance and gating charge were unaffected by changes in pHe. IKx did not depend on pHi. Given the importance of IKx in rod function, these results suggest that pHe could affect the signal transmitted from rods by changing IKx activation parameters. 相似文献
10.
Shebzukhov YV Koroleva EP Khlgatian SV Lagarkova MA Meshcheryakov AA Lichinitser MR Karbach J Jager E Kuprash DV Nedospasov SA 《Immunology letters》2005,100(1):88-93
Thymidylate synthase (TYMS), the critical enzyme for DNA synthesis and a target for chemotherapy, was recently characterized as an oncogene and a potential target for specific immunotherapy. Here we report TYMS-specific antibody response in a fraction of colon cancer patients. Humoral immune response to TYMS is induced by chemotherapy using TYMS inhibitors, such as 5-fluorouracil (5-FU), and may be associated with tumor burden. Therefore, TYMS may serve as a useful serological biomarker for monitoring the course of disease and treatment in cancer patients. 相似文献