scholarly journals Prodromal dysfunction of α5GABA-A receptor modulated hippocampal ripples in Alzheimer′s disease

2021 ◽  
Author(s):  
Marcia H Ratner ◽  
Scott S Downing ◽  
Ouyang Guo ◽  
KathrynAnn Odamah ◽  
Tara M Stewart ◽  
...  
Keyword(s):  
Early Stage ◽  
High Serum ◽  
Tonic Inhibition ◽  
Memory Dysfunction ◽  
Swedish Mutation ◽  
Familiar Environment ◽  
Ripple Amplitude ◽  
Exon 9 ◽  
Orally Bioavailable ◽  
Memory Enhancer

Decades of research attempting to slow the onset of Alzheimer′s disease (AD) indicates that a better understanding of memory will be key to the discovery of effective therapeutic approaches. Here, we ask whether prodromal neural network dysfunction might occur in the hippocampal trisynaptic circuit by using α5IA as a selective negative modulator of extrasynaptic α5GABA-A receptors in TgF344-AD transgenic rats, a model for early onset AD. The results demonstrate that orally bioavailable α5IA, an established memory enhancer, increases CA1 pyramidal cell mean firing rates and peak CA1 ripple amplitude during wakeful immobility in wild type F344 rats resting in a familiar environment. We show that TgF344-AD rats, which express human amyloid-beta precursor protein (with the Swedish mutation) and human presenilin-1 (with a Δ exon 9 mutation), exhibit high serum Aβ42 and Aβ40 levels by 3 months of age. By 9 months of age, CA1 ripples in young adult TgF344-AD rats are nonresponsive to α5IA indicating network dysfunction prior to the onset of AD pathology and memory dysfunction. These results demonstrate, to the best of our knowledge, the first evidence for prodromal α5GABA-A receptor dysfunction in the AD hippocampal trisynaptic circuit. Moreover, as α5GABA-A receptors are located extrasynaptically and subserve the function of tonic inhibition we posit that an early stage of memory dysfunction involves the disruption of tonic inhibition in the hippocampus.

scholarly journals Contribution of Impaired Early-Stage Visual Processing to Working Memory Dysfunction in Adolescents With Schizophrenia

2007 ◽  
Vol 64 (11) ◽  
pp. 1229 ◽  
Author(s):  
Corinna Haenschel ◽  
Robert A. Bittner ◽  
Fabian Haertling ◽  
Anna Rotarska-Jagiela ◽  
Konrad Maurer ◽  
...  
Keyword(s):  
Working Memory ◽  
Visual Processing ◽  
Early Stage ◽  
Memory Dysfunction

scholarly journals Serum Hydroxybutyrate dehydrogenase as an early predictive marker of the severity of acute pancreatitis: a retrospective study

2020 ◽  
Author(s):  
weiming xiao ◽  
Weili Liu ◽  
Ling Yin ◽  
Yong Li ◽  
Guotao Lu ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Retrospective Study ◽  
Organ Failure ◽  
Early Stage ◽  
Laboratory Data ◽  
Elevated Serum ◽  
High Serum ◽  
Normal Serum ◽  
Receiver Operating Curve ◽  
Persistent Organ Failure

Abstract Background: To investigate the value of serum hydroxybutyrate dehydrogenase (HBDH) level, an isozyme of lactate dehydrogenase (LDH), in evaluating the severity of acute pancreatitis (AP).Methods: Patients diagnosed with AP from January 2013 to December 2018 were included in this retrospective study. Patients were divided into the normal serum HBDH levels group (n-HBDH group) and the high serum HBDH levels group (h-HBDH group) according to the criteria HBDH ≥ 182 U/L after admission. The demographic parameters, laboratory data and the severity of AP in the two groups were compared. The receiver operating curve (ROC) was used to evaluate the efficacy of serum HBDH in predicting persistent organ failure and systemic inflammatory response syndrome (SIRS).Results: A total of 260 AP patients were enrolled, including 176 cases in the n-HBDH group and 84 cases in the h-HBDH group. The incidence of SIRS and organ failure in the h-HBDH group were significantly higher than those in n-HBDH group (both P < 0.001). In addition, the HBDH level was significantly decreased in 110 patients who were re-measured after AP treatment. The serum HBDH levels were positively correlated with Atlanta classification, Ranson score, and BISAP score (all P < 0.05). ROC analysis showed that a serum HBDH cut-off point of 195.0 U/L had optimal predictive value for the development of persistent organ failure (AUC = 0.778) and 166.5 U/L for the development of SIRS (AUC = 0.724).Conclusion: The elevated serum HBDH in early stage of AP is closely related to the adverse prognosis of AP patients, which can be used as a potential early biomarker for predicting the severity of AP.

scholarly journals Serum hydroxybutyrate dehydrogenase as an early predictive marker of the severity of acute pancreatitis: a retrospective study

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Weiming Xiao ◽  
Weili Liu ◽  
Ling Yin ◽  
Yong Li ◽  
Guotao Lu ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Retrospective Study ◽  
Organ Failure ◽  
Early Stage ◽  
Laboratory Data ◽  
Elevated Serum ◽  
High Serum ◽  
Normal Serum ◽  
Receiver Operating Curve ◽  
Persistent Organ Failure

Abstract Background To investigate the value of serum hydroxybutyrate dehydrogenase (HBDH) level, an isozyme of lactate dehydrogenase, in evaluating the severity of acute pancreatitis (AP). Methods Patients diagnosed with AP from January 2013 to December 2018 were included in this retrospective study. Patients were divided into the normal serum HBDH levels group (n-HBDH group) and the high serum HBDH levels group (h-HBDH group) according to the criteria HBDH ≥ 182 U/L after admission. The demographic parameters, laboratory data and the severity of AP in the two groups were compared. The receiver operating curve (ROC) was used to evaluate the efficacy of serum HBDH in predicting persistent organ failure and systemic inflammatory response syndrome (SIRS). Results A total of 260 AP patients were enrolled, including 176 cases in the n-HBDH group and 84 cases in the h-HBDH group. The incidence of SIRS and organ failure in the h-HBDH group were significantly higher than those in n-HBDH group (both P < 0.001). In addition, the HBDH level was significantly decreased in 110 patients who were re-measured after AP treatment. The serum HBDH levels were positively correlated with Atlanta classification, Ranson score, and BISAP score (all P < 0.05). ROC analysis showed that a serum HBDH cut-off point of 195.0 U/L had optimal predictive value for the development of persistent organ failure (AUC = 0.778) and 166.5 U/L for the development of SIRS (AUC = 0.724). Conclusion The elevated serum HBDH in early stage of AP is closely related to the adverse prognosis of AP patients, which can be used as a potential early biomarker for predicting the severity of AP.

Aspartyl (Asparaginyl) ß hydroxylase (AABH) as a serum bio-marker for prostate cancer to identify prostate cancer, regardless of PSA level.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 10-10
Author(s):  
Mahmood Moshiri ◽  
Kiarash Moshiri ◽  
Arsha Moshiri ◽  
Hassan Monhemi ◽  
Mohammad Hadi Sekhavati
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Sandwich Elisa ◽  
Specific Antigen ◽  
High Serum ◽  
Cancer Tissue ◽  
Serum Samples ◽  
Psa Testing ◽  
Detect Prostate Cancer

10 Background: Background: Prostate Specific Antigen (PSA) is a molecular marker of prostate cancer (PC). I most countries, standard of care suggests annual PSA testing in all men over 50 years of age; and for men at high risk, the test is recommended from 40 years of age. Due to low Specificity and low sensitivity of the PSA test, a large number of unnecessary biopsies occur every year. This low specificity can be due to the fact that PSA is found in both benign and malignant lesions of Prostate tissue. To date measurement of the percentage of free PSA, have resulted an small improvements in specificity of PSA testing. Thus, the development of a simple blood test to detect prostate cancer that exhibits higher specificity compared to PSA could have the potential of reducing biopsies performed due to false positive screening results and improve the quality of medical care. Methods: We have investigated the utility of aspartyl (asparaginyl) β-hydroxylase (AABH) as a prostate cancer biomarker. AABH has been detected by immunohistochemical staining (IHC) in a broad range of cancers including Prostate Adenocarcinoma through out the world. AABH have been detected by IHC in more than 97% of tumor specimens tested (n > 200) while absent in normal and non cancer tissue. We have developed a sandwich ELISA test for the detection of AABH in serum samples. Preliminary results showed an accuracy of 91- 94% for detecting cancer patients from non-cancer patients in different types of Cancer. Here we have utilized this assay to detect AABH levels in the sera of patients diagnosed with Prostate cancer (biopsy proven, pre-treatment samples), compared to non-cancer individuals. Results: AABH was detected above a threshold level of 1.2 ng/mL in 91% of the sera of PC patients (n = 60), in all different stages and grades of Prostate Cancer. All non-cancer individuals (n = 30) had AABH values below the threshold. Further study of direct comparison of AABH to PSA levels (n = 4,000) is underway. Conclusions: Our data suggest that measurement of serum AABH levels may help to detect Prostate Cancer in early stage and potentially reduce the number of prostate biopsies performed due to increased high serum PSA.

scholarly journals 486Serum levels of miRNA-221 and -222 may be predictive biomarkers for cognitive decline

2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Yuya Ishihara ◽  
Hiroya Yamada ◽  
Eiji Munetuna ◽  
Chiharu Hagiwara ◽  
Ryosuke Fujii ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Early Stage ◽  
Predictive Biomarkers ◽  
Serum Levels ◽  
High Serum ◽  
Short Version ◽  
Health Examination ◽  
Potential Candidate ◽  
Odds Ratios ◽  
Serum Mirna

Abstract Background Although dementia is a huge problem in public health, no fundamental biomarker has been established to detect cognitive decline at the early stage. MicroRNAs (miRNAs) regulate gene expression, and are associated with the development of various diseases. Methods The subjects of this prospective study were 162 (75 men, 87 women) residents who attended a health examination in Yakumo town in Hokkaido, in 2012 and re-attended at least once while 2013 to 2015. Serum samples were collected in 2012 and serum miRNA were measured by qRT-PCR. We used a short version of the Mini-Mental State Examination (SMMSE) to screen cognitive function, and calculated the change in SMMSE score per year. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) of serum miRNA levels for cognitive decline (decrease of greater than 0.5 points per year) using the lowest tertile group of miRNAs as the reference by logistic regression analysis. Results The mean age and change in SMMSE score of the subjects was 63.9±9.6 years and -0.03±1.19 points. Odds ratios (ORs) for cognitive decline were significantly higher in the highest tertile of serum miR-221 (OR = 3.24, 95%CI=1.20-8.72) and miR-222 (OR = 4.01, 95%CI=1.36-11.80) even if confounding factors were adjusted. Conclusions High serum levels of miR-221 and -222 were significantly associated with cognitive decline. Key messages High serum levels of miR-221 and -222 may be potential candidate biomarkers for prediction of cognitive decline.

scholarly journals Activation of fibroblast growth factor-inducible 14 in the early phase of childhood IgA nephropathy

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258090
Author(s):  
Yuko Tezuka ◽  
Minenori Eguchi-Ishimae ◽  
Erina Ozaki ◽  
Toshiyuki Ito ◽  
Eiichi Ishii ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Iga Nephropathy ◽  
Kidney Diseases ◽  
Early Stage ◽  
High Serum ◽  
Fibroblast Growth ◽  
Expression Array ◽  
Expression Arrays ◽  
Gene Expression Arrays

IgA nephropathy (IgAN) is the most common form of glomerulonephritis worldwide. Pediatric patients in Japan are diagnosed with IgAN at an early stage of the disease through annual urinary examinations. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and fibroblast growth factor-inducible 14 (Fn14) have various roles, including proinflammatory effects, and modulation of several kidney diseases; however, no reports have described their roles in pediatric IgAN. In this study, we performed pathological and immunohistochemical analyses of samples from 14 pediatric IgAN patients. Additionally, gene expression arrays of glomeruli by laser-captured microdissection were performed in hemi-nephrectomized high serum IgA (HIGA) mice, a model of IgA nephropathy, to determine the role of Fn14. Glomeruli with intense Fn14 deposition were observed in 80% of mild IgAN cases; however, most severe cases showed glomeruli with little or no Fn14 deposition. Fn14 deposition was not observed in obvious mesangial proliferation or the crescent region of glomeruli, but was detected strongly in the glomerular tuft, with an intact appearance. In HIGA mice, Fn14 deposition was observed mildly beginning at 11 weeks of age, and stronger Fn14 deposition was detected at 14 weeks of age. Expression array analysis indicated that Fn14 expression was higher in HIGA mice at 6 weeks of age, increased slightly at 11 weeks, and then decreased at 26 weeks when compared with controls at equivalent ages. These findings suggest that Fn14 signaling affects early lesions but not advanced lesions in patients with IgAN. Further study of the TWEAK/Fn14 pathway will contribute to our understanding of the progression of IgAN.

scholarly journals Predictive Value of Serum Infliximab Levels at Induction Phase in Rheumatoid Arthritis Patients

2017 ◽  
Vol 11 (1) ◽  
pp. 75-87 ◽  
Author(s):  
Teresa Jurado ◽  
Chamaida Plasencia-Rodríguez ◽  
Ana Martínez-Feito ◽  
Victoria Navarro-Compán ◽  
Theo Rispens ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Outcomes ◽  
Predictive Value ◽  
Early Stage ◽  
Multivariable Analysis ◽  
Roc Curves ◽  
Drug Clearance ◽  
High Serum ◽  
Induction Phase ◽  
Trough Levels

Background:The Infliximab, has proven effective in treating rheumatoid arthritis (RA). A good clinical response is usually associated with high serum drug levels. Development of antibodies toward Infliximab (ATI) can increase drug clearance, leading to treatment failure.Aims:To analyze whether serum Infliximab trough levels (ITL) at the induction phase are associated with Infliximab clearance and clinical outcomes at week(W) 54 and to investigate the association with immunogenicity development.Methods:Observational retrospective study in which ITL from 66 RA patients were measured by capture ELISA at W0, W2, W6, W14 and 22. Patients were classified as ITLpos if Infliximab was detectable at W54 and ITLneg otherwise. ATI were assayed by bridging ELISA and by two drug-tolerant assays. ITL cut-off values were established by ROC curves. The association between ITL at early-stage and clearance of Infliximab at W54 was analyzed by univariable and multivariable logistic regression.Results:ITLneg patients (n=25) always had significantly lower Infliximab levels than ITLpos (n=41). An ITL value of 4.4 μg/mL at W6 best predicted W54 Infliximab absence. In the multivariable analysis, only ITL below the cut-off at W6 (OR: 86.6; 95%CI: 6.58-1139.99) and non-use of methotrexate (OR: 6.9; 95%CI: 1.04-45.84) remained significantly associated with W54 Infliximab absence. ATI were more frequent in patients with ITL below the cut-off at W6.Conclusions:In RA, ITL at induction phase are inversely associated with Infliximab clearance and clinical outcomes at W54. ATI was the main reason for low early ITL. A predictive value of ITL at W6 was found as a useful prognostic measure of treatment efficacy.

Progressive Spatial Memory Impairment, Brain Amyloid Deposition and Changes in Serum Amyloid Levels as a Function of Age in APPswe/PS1dE9 Mice

2018 ◽  
Vol 15 (11) ◽  
pp. 1053-1061 ◽  
Author(s):  
Lu Fu ◽  
Yao Sun ◽  
Yongqing Guo ◽  
Bin Yu ◽  
Haihong Zhang ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Amyloid Β ◽  
Serum Levels ◽  
Cognitive Capacity ◽  
Age Cohorts ◽  
Learning Capacity ◽  
Amyloid Deposits ◽  
Parallel Increase ◽  
Swedish Mutation ◽  
Exon 9

Background: Mice co-expressing human amyloid precursor protein with the Swedish mutation (APPswe) and exon-9-deleted presenilin (PS1dE9) has become one of the most widely used mouse models for studying Alzheimer’s disease (AD) pathogenesis and preclinical studies of AD therapeutic approaches. Objective: In this study, we systematically investigated cognitive decline, amyloid-β (Aβ) deposition and cerebral or Aβ serum levels as well as the relationships among these measures in APPswe/PS1dE9 transgenic mice. Method: APPswe/PS1dE9 mice were separated into four equal age cohorts (4, 6, 9, and 12 months). We assessed cognitive capacity, deposited plaques, and the levels of Aβ40/Aβ42 in brain tissue and serum of mice at different ages. Results: APPswe/PS1dE9 mice exhibited declined memory beginning at 6 months of age, with cognitive capacity remarkably impaired at 12-months. Coincidently, amyloid deposits began to develop in transgenic mice brain at 6-months and increased with age. In addition, Aβ42 levels in brains of APPswe/ PS1dE9 mice increased with age with no parallel increase in Aβ40. The concentration of serum Aβ42 declined from 4 to 6 months of age, but a similar age-dependent decrease was not observed for Aβ40. Conclusion: APPswe/PS1dE9 transgenic mice began to develop amyloid plaques at 6 months of age and exhibited a corresponding impairment of spatial learning capacity. Serum Aβ42 level decreased remarkably from 4 to 6 months, at which stage Aβ42 began to accumulate in the brain and deposit as plaques.

scholarly journals A Novel Circulating MiRNA-Based Signature for the Diagnosis and Prognosis Prediction of Early-Stage Cervical Cancer

2020 ◽  
Vol 19 ◽  
pp. 153303382097066
Author(s):  
Huajuan Qiu ◽  
Duoxian Liang ◽  
Limin Liu ◽  
Qun Xiang ◽  
Zhijun Yi ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Healthy Subjects ◽  
Early Stage ◽  
High Serum ◽  
The Cancer Genome Atlas ◽  
Molecular Signature ◽  
Circulating Mirna ◽  
Prognosis Prediction ◽  
Diagnosis And Prognosis ◽  
Low Serum

Background: MicroRNAs (miRNAs) have been shown to play a key role in regulating the progression of cervical cancer (CC). This study aimed to develop a circulating miRNA-based molecular signature for the diagnosis and prognosis prediction of early-stage CC. Methods: This study included 112 patients diagnosed with early-stage CC, 45 patients confirmed with cervical intraepithelial neoplasia (CIN) and 90 healthy subjects. Compared to the normal controls, the expression level of miR-21 was increased, while the levels of miR-125b and miR-370 were decreased in CC in both GSE30656 and The Cancer Genome Atlas (TCGA) cohort. The expression levels and diagnostic value of these candidate miRNAs were then validated through qRT-PCR. Their diagnostic and prognostic values for early-stage CC were further explored. Results: Compared to the patients with CIN and healthy subjects, serum miR-21 was increased, while serum miR-125b and serum miR-370 were reduced in early-stage CC. In addition, combining these molecules yielded good performance for differentiating early-stage CC from CIN or healthy subjects. Moreover, strong association was found between serum miR-21 and lymph node metastasis (LNM) as well as recurrence-free survival of early-stage CC. Similar observations were found for serum miR-125b and serum miR-370. Patients with simultaneously high serum miR-21 + low serum miR-125b + low serum miR-370 suffered a high risk of LNM and recurrence, while those with low serum miR-21 + high serum miR-125b + high serum miR-370 had little risk for LNM and recurrence. Conclusions: Combining serum miR-21, miR-125b and miR-370 as a miRNA-based signature is promising for the detection and prognosis prediction of early-stage CC.

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