scholarly journals Propensity for somatic expansion increases over the course of life in Huntington disease

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Radhia Kacher ◽  
François-Xavier Lejeune ◽  
Sandrine Noël ◽  
Cécile Cazeneuve ◽  
Alexis Brice ◽  
...  
Keyword(s):  
Computational Model ◽  
Recent Work ◽  
Huntington Disease ◽  
Blood Cells ◽  
Cag Repeat ◽  
Post Mortem ◽  
Blood Samples ◽  
Somatic Instability ◽  
Mutation Carriers ◽  
Better Than

Recent work on Huntington disease (HD) suggests that somatic instability of CAG repeat tracts, which can expand into the hundreds in neurons, explains clinical outcomes better than the length of the inherited allele. Here, we measured somatic expansion in blood samples collected from the same 50 HD mutation carriers over a twenty-year period, along with post-mortem tissue from 15 adults and 7 fetal mutation carriers, to examine somatic expansions at different stages of life. Post-mortem brains, as previously reported, had the greatest expansions, but fetal cortex had virtually none. Somatic instability in blood increased with age, despite blood cells being short-lived compared to neurons, and was driven mostly by CAG repeat length, then by age at sampling and by interaction between these two variables. Expansion rates were higher in symptomatic subjects. These data lend support to a previously proposed computational model of somatic instability-driven disease.

Msh2 deficiency prevents in vivo somatic instability of the CAG repeat in Huntington disease transgenic mice

10.1038/70598 ◽  
1999 ◽  
Vol 23 (4) ◽  
pp. 471-473 ◽  
Author(s):  
Kevin Manley ◽  
Thomas L. Shirley ◽  
Lorraine Flaherty ◽  
Anne Messer
Keyword(s):  
Transgenic Mice ◽  
Huntington Disease ◽  
Cag Repeat ◽  
Somatic Instability

A Better Solution to the General Problem of Creation

2017 ◽  
Vol 9 (1) ◽  
pp. 147-162
Author(s):  
Jeremy W. Skrzypek
Keyword(s):  
Recent Work ◽  
General Problem ◽  
The State ◽  
State Of Affairs ◽  
Better Than

It is often suggested that, since the state of affairs in which God creates a good universe is better than the state of affairs in which He creates nothing, a perfectly good God would have to create that good universe. Making use of recent work by Christine Korgaard on the relational nature of the good, I argue that the state of affairs in which God creates is actually not better, due to the fact that it is not better for anyone or anything in particular. Hence, even a perfectly good God would not be compelled to create a good universe.

Real-time Red Blood Cell Counting and Osmolarity Analysis using a Photoacoustic-based Microfluidic System

Lab on a Chip ◽  
2021 ◽  
Author(s):  
Wenxiu Zhao ◽  
Haibo Yu ◽  
Yangdong Wen ◽  
Hao Luo ◽  
Boliang Jia ◽  
...  
Keyword(s):  
Blood Cell ◽  
Physical Properties ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Diagnostic Procedure ◽  
Microfluidic System ◽  
Cell Counting ◽  
Blood Samples ◽  
System P ◽  
Blood Cell Counting

Counting the number of red blood cells (RBCs) in blood samples is a common clinical diagnostic procedure, but conventional methods are unable to provide the size and other physical properties...

scholarly journals Evaluation of the effect of an extract of sabugueiro (Sambucus australis) on the labeling of blood constituents with technetium-99m

2007 ◽  
Vol 50 (spe) ◽  
pp. 161-166
Author(s):  
Camila Godinho Ribeiro ◽  
Bernardo Machado Rebello ◽  
Rosane de Figueiredo Neves ◽  
Sebastião David Santos-Filho ◽  
Adenilson de Souza da Fonseca ◽  
...  
Keyword(s):  
Nuclear Medicine ◽  
Blood Cells ◽  
Trichloroacetic Acid ◽  
Wistar Rats ◽  
Blood Samples ◽  
Chemical Substances ◽  
Blood Constituents ◽  
Technetium 99M

Sambucus australis (sabugueiro) has been used to treat inflammatory and rheumatologic disorders. Blood constituents labeled with technetium-99m (99mTc) have been used in nuclear medicine to obtain diagnostic images. The aim of this work was to evaluate the effect of a sabugueiro extract on the labeling of blood cells with 99mTc. Blood samples from Wistar rats were incubated with sabugueiro extract and the radiolabeling assay of blood constituents was carried out. After centrifugation, samples of plasma and blood cells were separated. Aliquots of plasma and blood cells were precipitated with trichloroacetic acid and centrifuged to isolate soluble and insoluble fractions. The radioactivity in each fraction was counted and the percentage of activity (%ATI) was determined. Incubation with sabugueiro extract altered significantly (p<0.05) the %ATI incorporated to the blood constituents. These results could be explained due the presence of chemical substances in the sabugueiro extract that present redox and/or chelating action altering the labeling of the blood constituents with 99mTc.

Probing the extracellular release site of the plasma membrane calcium pump

2000 ◽  
Vol 278 (5) ◽  
pp. C965-C972 ◽  
Author(s):  
Wanyan Xu ◽  
Betty Jo Wilson ◽  
Lin Huang ◽  
Emma L. Parkinson ◽  
Brent J. F. Hill ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Blood Cells ◽  
High Field ◽  
Release Site ◽  
Calcium Pump ◽  
Maximal Inhibition ◽  
Human Red Blood Cells ◽  
Access Channel ◽  
Extracellular Release ◽  
Better Than

The plasma membrane Ca2+ pump is known to mediate Ca2+/H+ exchange. Extracellular protons activated 45Ca2+ efflux from human red blood cells with a half-maximal inhibition constant of 2 nM when the intracellular pH was fixed. An increase in pH from 7.2 to 8.2 decreased the IC50 for extracellular Ca2+ from ∼33 to ∼6 mM. Changing the membrane potential by >54 mV had no effect on the IC50 for extracellular Ca2+. This argues against Ca2+ release through a high-field access channel. Extracellular Ni2+ inhibited Ca2+ efflux with an IC50 of 11 mM. Extracellular Cd2+ inhibited with an IC50 of 1.5 mM, >10 times better than Ca2+. The Cd2+ IC50 also decreased when the pH was raised from 7.1 to 8.2, consistent with Ca2+, Cd2+, and H+ competing for the same site. The higher affinity for inhibition by Ni2+and Cd2+ is consistent with a histidine or cysteine as part of the release site. The cysteine reagent 2-(trimethylammonium)ethyl methanethiosulfonate did not inhibit Ca2+ efflux. Our results are consistent with the notion that the release site contains a histidine.

scholarly journals Incidence of Huntington disease in a northeastern Spanish region: a 13-year retrospective study at tertiary care centre

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Paula Sienes Bailo ◽  
Raquel Lahoz ◽  
Juan Pelegrín Sánchez Marín ◽  
Silvia Izquierdo Álvarez
Keyword(s):  
Retrospective Study ◽  
Huntington Disease ◽  
Tertiary Care ◽  
Genetic Diagnosis ◽  
Repeat Length ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Incomplete Penetrance ◽  
Predictive Test ◽  
Incident Cases

Abstract Background Despite the progress in the knowledge of Huntington disease (HD) in recent years, the epidemiology continues uncertain, so the study of incidence becomes relevant. This is important since various factors (type of population, diagnostic criteria, disease-modifying factors, etc.) make these data highly variable. Therefore, the genetic diagnosis of these patients is important, since it unequivocally allows the detection of new cases. Methods Descriptive retrospective study with 179 individuals. Incidence of HD was calculated from the ratio of number of symptomatic cases newly diagnosed per 100,000 inhabitants per year during the period 2007–2019 in Aragon (Spain). Results 50 (27.9%) incident cases of HD (CAG repeat length ≥ 36) were identified from a total of 179 persons studied. The remaining 129/179 (72.1%) were HD negative (CAG repeat length < 36). 29 (58.0%) females and 21 (42.0%) males were confirmed as HD cases. The overall incidence was 0.648 per 100,000 patient-years. 11/50 positive HD cases (22.0%) were identified by performing a predictive test, without clinical symptoms. The minimum number of CAG repeats found was 9 and the most common CAG length among HD negative individuals was 16. Conclusions Our incidence lied within the range reported for other Caucasian populations. Implementation of new techniques has allowed to determine the exact number of CAG repeats, which is especially important in patients with triplet expansions in an HD intermediate and/or incomplete penetrance allele, both in diagnostic, predictive and prenatal tests.

scholarly journals Reliable Measurements of theβ-Amyloid Pool in Blood Could Help in the Early Diagnosis of AD

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Pedro Pesini ◽  
Virginia Pérez-Grijalba ◽  
Inmaculada Monleón ◽  
Mercè Boada ◽  
Lluís Tárraga ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Early Diagnosis ◽  
Small Proportion ◽  
Blood Cells ◽  
Plasma Proteins ◽  
Blood Samples ◽  
Striking Result ◽  
Healthy Control ◽  
Amnesic Mild Cognitive Impairment

The present study was aimed at assessing the capability of Aβ1-40 and Aβ1-42 levels in undiluted plasma (UP), diluted plasma (DP), and cell bound (CB) to distinguish between early stages of Alzheimer's disease (AD), amnesic mild cognitive impairment (MCI), and healthy control (HC). Four blood samples from each participant were collected during one month and the levels of Aβ1-40 and Aβ1-42 were determined by a blinded proprietary ELISA sandwich (Araclon Biotech. Zaragoza, Spain). First striking result was that the amount of Aβ1-40 and Aβ1-42 in UP represented only a small proportion (~15%) of the total beta-amyloid pool in blood (βAPB) described here as the sum of Aβ1-40 and Aβ1-42 in blood where they are free in plasma, bound to plasma proteins, and bound to blood cells. Furthermore, we found that levels of Aβ1-40 and Aβ1-42 in UP, DP, and CB were significantly higher in MCI when compared to HC. On average, the totalβAPB was 1.8 times higher in MCI than in HC (P=0.03) and allowed to discriminate between MCI and HC with a sensitivity and specificity over 80%. Thus, quantification of several markers of theβAPB could be useful and reliable in the discrimination between MCI and HC.

scholarly journals Acetylsalicylic acid and morphology of red blood cells

2010 ◽  
Vol 53 (3) ◽  
pp. 575-582 ◽  
Author(s):  
Jacques Natan Grinapel Frydman ◽  
Adenilson de Souza da Fonseca ◽  
Vanessa Câmara da Rocha ◽  
Monica Oliveira Benarroz ◽  
Gabrielle de Souza Rocha ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Control Group ◽  
Blood Samples ◽  
Morphological Alterations ◽  
Blood Smears ◽  
In Vivo Treatment ◽  
Microscopy Data

This work evaluated the effect of in vitro and in vivo treatment with ASA on the morphology of the red blood cells. Blood samples or Wistar rats were treated with ASA for one hour. Blood samples or animals treated with saline were used as control group. Blood smears were prepared, fixed, stained and the qualitative and quantitative morphology of red blood cells were evaluated under optical microscopy. Data showed that the in vitro treatment for one hour with ASA at higher dose used significantly (p<0.05) modified the perimeter/area ratio of the red blood cells. No morphological alterations were obtained with the in vivo treatment. ASA use at highest doses could interfere on shape of red blood cells.

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