Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The diagnostic value of a strikingly elevated serum lactate dehydrogenase (LDH) level in association with only small or no increases in SGOT and alkaline phosphatase levels was noted in five patients with proved renal infarction. Four had renal artery embolism and infarction in association with atrial arrhythmias; one had an acute extension of an abdominal aortic aneurysm occluding the renal artery. Other causes of a considerable isolated increase in the serum LDH level such as hemolysis and myocardial infarction can usually be easily excluded.
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PMID:Elevation of serum lactate dehydrogenase levels in renal infarction. 44 17

An electrophoretic variant of lactate dehydrogenase (LD) M(A) subunit was discovered in a female patient with chest pain. Her LD activity in serum was within the normal reference interval, and analysis of her LD isoenzyme pattern showed an abnormal migration indicating a fast-type LD-M(A) subunit variant. DNA analysis of the mutant LD-M gene detected a single base substitution, an A to G transition at codon 220 (AAA-->GAA). This mutation resulted in the replacement of a lysine by a glutamic acid (mutation K220E) and produced a subunit variant (electrophoretic fast type). This missense mutation was also observed in the patient's son, and genotypes of mother and son were consistent with their biochemical phenotypes, as evaluated by LD isoenzyme analysis.
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PMID:Fast-type electrophoretic variant of lactate dehydrogenase M(A) and comparison with other missense mutations in lactate dehydrogenase M(A) and H(B) genes. 790 13

An electrophoretic variant of the lactate dehydrogenase (LDH)-B(H) subunit was discovered in a patient with diabetes mellitus. His LDH activity in serum was slightly lower than normal and the LDH isozyme pattern showed an abnormal migration indicating an LDH-B subunit variant of the fast type. The LDH containing the variant subunit revealed a decreased heat stability. DNA analysis of the variant allele detected a base substitution, an A to G transition, at codon 6 (AAA-->GAA). The mutation resulted in the replacement of a lysine by a glutamic acid (K6E). The change may cause the heat instability and affect the net charge of the variant subunit, resulting in an electrophoretic LDH-B subunit variant of the fast type.
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PMID:Analysis of a genetic mutation in an electrophoretic variant of the human lactate dehydrogenase-B(H) subunit. 831 53

Ischemia-reperfusion injuries can occur with diseases such as myocardial infarction and stroke and during surgical procedures such as organ transplantation and correction of aortic aneurysms. We developed a murine model to mimic abdominal aortic aneurysm repair with cross-clamping of the aorta distal to the renal artery. After model development, we compared the normal complement BALB/c mouse with the C5-deficient DBA/2N mouse. To assess quantitative differences, we measured neuromuscular function up to 72 h after ischemia with a subjective clinical scoring system, as well as plasma chemistries, hematology, and histopathology. There were significant increases in clinical scores and creatine phosphokinase, lactate dehydrogenase, and muscle histopathology scores in BALB/c mice compared with those in DBA/2N mice and sham-surgery mice. Muscle histopathology scores of the cranial tibialis and quadriceps correlated well with clinical signs, creatine phosphokinase, and lactate dehydrogenase, and indicated the greatest pathology in these muscle groups. We developed a murine model of skeletal muscle ischemia-reperfusion injury that can utilize the benefits of murine genetic and transgenic models to assess therapeutic principles of this model. Additionally, we have shown a significant reduction in clinical signs, plasma muscle enzyme concentrations, and muscle pathology in the C5-deficient DBA/2N mouse in this model.
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PMID:A murine skeletal muscle ischemia-reperfusion injury model: differential pathology in BALB/c and DBA/2N mice. 980 69

This paper reviews the current state of the use of organotypic brain slice cultures for neurotoxicological and neuropharmacological screening and mechanistic studies, as exemplified by excitotoxin application. At present, no in vitro systems have been approved by the regulatory authorities for neurotoxicity testing. For the evaluation of the slice culture method, organotypic hippocampal slice cultures were exposed to toxic doses of the excitotoxins, glutamate, N-methyl-D-aspartate (NMDA), kainic acid and 2-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), and the glial toxin, DL-alpha-aminoadipic acid (DLAAA). Neuronal cell death was quantified by propidium iodide (PI) uptake, and visualised by Fluoro-Jade (FJ) staining. General cell death was monitored by lactate dehydrogenase (LDH) release into the culture medium. EC50 values for the different compounds, based on PI uptake after exposure for 48 hours in entire cultures, were: glutamate, 3.5 mM; DL-AAA, 2.3 mM; kainic acid, 13 microM; NMDA, 11 microM; and AMPA, 3.7 microM. In the slice cultures, the hippocampal subfields displayed the same differences in vulnerability as those observed in vivo. When subfield analysis was performed on the cultures, the CA1 subfield was most susceptible to glutamate, NMDA and AMPA, while CA3 was most susceptible to kainic acid. The amount of LDH release for DL-AAA was about four times that of L-glutamate, in accordance with the additional toxic effect on glial cells, which was also found by confocal microscopy to stain for FJ. In conclusion, it was found that organotypic brain slice culture, combined with standardised protocols and quantifiable markers, such as PI and FJ staining, is a relevant and feasible in vitro system for neurotoxicity testing. Considering the amount and quality of the available published data, it is recommended that the brain slice culture method could be subjected to pre-validation and formal validation for inclusion in a tiered in vitro neurotoxicity testing scheme to supplement and replace conventional animal tests.
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PMID:Organotypic brain slice cultures: an efficient and reliable method for neurotoxicological screening and mechanistic studies. 1565 16

Abdominal aortic aneurysm (AAA) is characterized as dilation of the aortic wall. Dysregulation of vascular smooth muscle cells (VSMCs) can contribute to the development of this phenotype. Circular RNAs and microRNAs (miRNAs) can regulate the proliferation and apoptosis of VSMCs. This present study aimed to identify the mechanisms of action behind the regulation of cerebellar degeneration-related protein 1 antisense RNA (CDR1as)/miRNA (miR)-7 in VSMCs. The expression levels of miR-7 were upregulated, whereas the levels of CDR1as and cytoskeleton-associated protein 4 (CKAP4) were downregulated in aortic specimens obtained from 10 patients who underwent surgery for AAA compared with aortic specimens from 10 control patients who underwent coronary artery bypass surgery. The molecular mechanism of action of CDR1as/miR-7 was investigated in primary VSMCs. The results of Cell Counting kit-8 and cell growth curve assays revealed that overexpression of CDR1as and knockdown of miR-7, increased VSMC proliferation, whereas knockdown of CDR1as and overexpression of miR-7 suppressed VSMC proliferation. In addition, overexpression of CDR1as and knockdown of miR-7, suppressed apoptosis in VSMCs, indicated by the decreased levels of reactive oxygen species (ROS) and lactate dehydrogenase (LDH) activity, whereas knockdown of CDR1as and overexpression of miR-7 exhibited the opposite effects. The results of luciferase reporter and biotin pull-down assays confirmed that CDR1as directly bound to miR-7 and suppressed its expression. Additionally, the CDR1as-induced proliferation and suppressed apoptosis was reversed by the overexpression of miR-7. Furthermore, luciferase reporter, reverse transcription-quantitative PCR and western blot assays revealed that miR-7 directly targeted CKAP4 and suppressed its expression. Additionally, the miR-7-suppressed proliferation and increased ROS and LDH activity were reversed by the overexpression of CKAP4. CDR1as also decreased caspase 3/7 activity, which was reversed by miR-7 mimics. miR-7 increased the activity of caspase 3/7, which was again reversed by the overexpression of CKAP4. Therefore, CDR1as, miR-7 and CKAP4 may act in the same pathway to regulate VSMC proliferation and apoptosis.
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PMID:CDR1as/miR-7/CKAP4 axis contributes to the pathogenesis of abdominal aortic aneurysm by regulating the proliferation and apoptosis of primary vascular smooth muscle cells. 3234 40