Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Restriction endonuclease analysis was used to detect alpha-gene deletions and to determine the haplotypes in the DNA of the beta S-gene-cluster [Benin, Central African Republic (CAR), and Senegal] in 221 patients with sickle cell anemia (SS). The clinical expression of SS was modified by the beta S-gene-cluster polymorphisms and the alpha-gene status (alpha-thalassemia-2). The overall risk of soft tissue organ failure caused by the obliterative sickle vasculopathy (including stroke, renal failure, chronic lung disease with cor pulmonale, leg ulcers, and young adult death) was increased threefold in those with a CAR haplotype and was decreased in those with a Senegalese chromosome (p = 0.003). In the presence of a Senegalese haplotype, the patient's health is better, and with the CAR haplotype it is always worse. With the Benin, it is intermediate. Acute recurrent clinical events including hospitalized sickle cell crisis, bone infarction, and infection are decreased in frequency in those with a Senegalese haplotype. The risk of most acute events including acute chest syndrome is equivalent in those with Benin or CAR haplotypes. In the United States, alpha-thalassemia-2 is co-inherited randomly among the beta S-gene-cluster haplotypes. Acute events occurring during childhood are minimally effected by this co-inheritance. The risk of soft tissue organ failure is decreased. After the age of 20 years, painful episodes of the lumbar dorsal area are increased in patients who had alpha-thalassemia-2 in association with degenerative bone disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beta S-gene-cluster haplotypes in sickle cell anemia: clinical implications. 170 Jun 39

Between March 1984 and February 1986, ten patients admitted to a spinal cord injury/stroke rehabilitation unit became bacteriuric with a strain of Serratia marcescens resistant to ampicillin, cephalothin, cefoxitin, ticarcillin, cotrimoxazole, gentamicin, and tobramycin. All the patients were catheterized, and in most, bacteriuria was asymptomatic. The organism was also recovered from their hospital environment (sinks, toilets, urine-collecting basins). Analysis of total plasmid content of multiresistant isolates revealed the presence of two plasmids (7 kilobase, 25.5 kilobase), not found in aminoglycoside susceptible strains of Serratia marcescens. Restriction endonuclease analysis and Southern hybridization (DNA probe: 25.5 kilobase plasmid) verified that these plasmids were identical. The 25.5 kilobase plasmid was purified, introduced by transformation into an Escherichia coli strain C recipient, and was found to mediate resistance to gentamicin and tobramycin. The emergence of multiresistant Serratia marcescens coincided with an increase in antibiotic usage on the ward. The reservoir seemed to be the urinary tracts of asymptomatic catheterized patients and their contaminated hospital environment.
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PMID:Molecular and epidemiologic study of multiresistant Serratia marcescens infections in a spinal cord injury rehabilitation unit. 327 39

Recently, evidence has been presented for genetic linkage between the angiotensinogen gene and primary hypertension in humans. In the present study we examined whether a similar linkage between blood pressure and the angiotensinogen gene locus can be demonstrated in a widely used animal model of primary hypertension, the stroke-prone spontaneously hypertensive rat (Heidelberg colony, SHRSPHD). In 115 F2 hybrids bred from SHRSPHD and a normotensive reference strain, the Wistar-KyotoHD (WKYHD) rat, systolic and diastolic blood pressures and heart rate were determined by indwelling arterial catheters in the presence and absence of dietary sodium loading. In addition, left and right ventricular heart weight was measured. Using a newly developed polymorphic marker assay for the angiotensinogen gene based on polymerase chain reaction amplification of an exon 2 fragment and subsequent restriction endonuclease digestion, we performed a cosegregation study in this cohort. No evidence for cosegregation between the angiotensinogen gene locus and blood pressure or any other phenotypic parameter assessed was found. Although the SHRSP serves as a valuable model of hypertension, our data emphasize that disease-relevant genetic loci in humans and rats cannot be assumed to coincide.
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PMID:Unlike human hypertension, blood pressure in a hereditary hypertensive rat strain shows no linkage to the angiotensinogen locus. 791 49

We describe a 15-year-old boy with full-blown mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and chronic progressive external ophthalmoplegia (CPEO). He presented with visual disturbance, hearing impairment, continuous partial epilepsy on the right aspect of the face, and right hemiparesis since the age of 13. Four months later, he experienced another strokelike episode with continuous partial epilepsy on the left hand. Serial computed tomographic scans revealed bilateral parieto-occipital hypodense lesions with gyral enhancement and an additional low-density lesion in the right frontal area 4 months later, respectively. Results of laboratory examinations disclosed lactic acidosis and mitochondrial myopathy with many ragged-red fibers. To identify the defective gene in mitochondrial DNA, a simple molecular test was performed by using restriction endonuclease Apa I. A transition from A to G was found at nucleotide position 3243 of the tRNA(Leu) gene. Interestingly, the patient also had marked external ophthalmoplegia and ptosis commonly found in patients with CPEO. Therefore, we suggest that ophthalmoplegia also occurs in the MELAS syndrome.
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PMID:Ophthalmologic manifestations in MELAS syndrome. 836 52

Previous studies have suggested that brain cells undergo apoptotic cell death during several neurodegenerative disorders such as Alzheimer's disease, Parkinsonism and ischemic stroke. In the present study, apoptotic DNA fragmentation and activation of nuclear endonuclease were evaluated in rat brain cells after head trauma. Severe closed head injury was induced in rats by the impact of a 450-g weight dropped from a height of 2 m. A 12% mortality was experienced after head trauma. Brain cell nuclei and DNA were isolated at intervals of 3, 10, 24 h, 3 and 10 days after head trauma. DNA fragmentation was measured by the random oligonucleotide-primed synthesis (ROPS) assay and was significantly increased with the maximum level of DNA fragmentation occurring at 10 h after trauma. The DNA and nuclei yields decreased 10 h after injury and remained at a reduced level at all subsequent sampling intervals. The DNA fragmentation induced after severe head trauma was accompanied by an increase in the activity of the Ca/Mg-dependent endonuclease associated with apoptosis. These data indicate that severe head injury is associated with significant brain cell death by apoptosis.
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PMID:DNA fragmentation and nuclear endonuclease activity in rat brain after severe closed head injury. 887 83

Background: Several mutations in mitochondrial DNA (mtDNA) are associated with the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). The "common" MELAS mutation, A3243G in the tRNA leucine (UUR) gene, affects approximately 80% of cases and is associated with respiratory chain complex I deficiency. Methods and Results: The A3243G mutation creates an ApaI restriction endonuclease site and can be detected by polymerase chain reaction (PCR) amplification of a region of mtDNA containing nt 3243, followed by ApaI digestion and electrophoretic analysis of the resulting fragments. Analysis of mtDNA from a child with complex I deficiency indicated the presence of the mutation homoplasmically in heart, liver, and skeletal muscle. Sequencing revealed only normal tRNA leucine (UUR) sequence, and a novel variant at nt 3426 in the ND1 subunit of complex I, which creates an ApaI site. ApaI digestion results in fragments of similar size to those found in patients with the A3243G mutation. Conclusions: A novel variant at nt 3426 of mtDNA creates an ApaI site and can potentially cause a false-positive result for the presence of the A3243G mutation. Given the highly polymorphic nature of mtDNA, care must be exercised in choosing primers for restriction endonuclease-based diagnostic tests for point mutations, and confirmation of a mutation by an independent method is recommended.
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PMID:A False-Positive Diagnosis for the Common MELAS (A3243G) Mutation Caused by a Novel Variant (A3426G) in the ND1 Gene of Mitochondria DNA. 1008 79

Despite the immediate event, such as cerebral trauma, cardiac arrest, or stroke that may result in neuronal or vascular injury, specific cellular signal transduction pathways in the central nervous system ultimately influence the extent of cellular injury. Yet, it is a cascade of mechanisms, rather than a single cellular pathway, which determine cellular survival during toxic insults. Although neuronal injury associated with several disease entities, such as Alzheimer's disease, Parkinson's disease, and cerebrovascular disease was initially believed to be irreversible, it has become increasingly evident that either acute or chronic modulation of the cellular and molecular environment within the brain can prevent or even reverse cellular injury. In order to develop rational, efficacious, and safe therapy against neurodegenerative disorders, it becomes vital to elucidate the cellular and molecular mechanisms that control neuronal and vascular injury. These include the pathways of free radical injury, the independent mechanisms of programmed cell death, and the downstream signal transduction pathways of endonuclease activation, intracellular pH, cysteine proteases, the cell cycle, and tyrosine phosphatase activity. Employing the knowledge gained from investigations into these pathways will hopefully further efforts to successfully develop effective treatments against central nervous system disorders.
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PMID:The dynamics of cellular injury: transformation into neuronal and vascular protection. 1133 19

To narrow the area known to contain the blood pressure quantitative trait locus (QTL) on rat chromosome 1, we constructed a fine linkage map covering the blood pressure OTL region on the chromosome using 22 genetic markers informative for stroke-prone spontaneously hypertensive rats of the Izumo colony (SHRSP/Izm) and Wistar-Kyoto rats of the Izumo colony (WKY/Izm). Linkage mapping was done by genotyping 626 backcrossed rats from matings between SHRSP/Izm and WKY/Izm. Nineteen genetic markers informative for the two strains were selected from public databases. Two markers were newly isolated by screening a rat genomic library. One marker was mapped using a restriction endonuclease polymorphism. The region between DlWox29 and D1Smu11 was covered with 22 informative markers placed every 0.6 cM on average. In addition, 6 physiological candidates for a hypertension gene were mapped in this region either by linkage or by radiation hybrid (RH) mapping. This information should be essential for the construction and analysis of congenic strains for this QTL region.
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PMID:Fine linkage mapping of the blood pressure quantitative trait locus region on rat chromosome 1. 1235 48

The risk of cardiovascular disease (CVD) in SLE patients is very high. It is therefore surprising that IL-10 has been discussed both as pathogenic in SLE and as an atheroprotective cytokine. In contrast, TNF is believed to be atherogenic and we recently reported that raised activity in the TNF-system is implicated in SLE-related CVD. Twenty-six (aged 52 +/- 8 years) female patients with SLE and a history of CVD (myocardial infarction, angina, stroke or claudication) were compared with 26 age-matched SLE patients without CVD (SLE controls) or 26 age-matched population controls. The -1087IL-10 gene polymorphism was determined by PCR with restriction endonuclease mapping. Serum IL-10 and TNF-levels were determined by ELISA. The A allele frequency of -1087IL-10 gene in SLE/CVD was higher than in SLE controls (0.62 versus 0.42, p < 0.05). Ten (38%) of 26 SLE/CVD exhibited IL-10 AA genotype compared with five (19%) of 26 SLE controls. Serum IL-10 and TNF-levels were raised in SLE/CVD compared with SLE controls or population controls (p < 0.001). Furthermore, in SLE/CVD, a significantly reduced IL-10:TNF ratio was observed in patients with IL-10 AA genotype compared with AG or GG genotype (0.56 versus 0.77 versus 1.24, p < 0.05). In SLE controls and population controls, individuals with IL-10 GG genotype tended to have higher IL-10:TNF ratio. In conclusion, the A-1087IL-10 allele which has been reported to cause a lower capacity for IL-10 production could contribute to CVD in SLE. Furthermore, the IL-10 AA genotype is associated with reduced ratio of atheroprotective to atherogenic cytokines in SLE patients with CVD.
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PMID:The A-1087IL-10 allele is associated with cardiovascular disease in SLE. 1553 Sep 17

The capacity for DNA repair is likely to be one of the factors that determine the vulnerability of neurons to ischemic stress and may influence the pathological outcome of stroke. In this report, initiation of base excision repair (BER) was assessed by analysis of enzyme activity and gene expression level of DNA glycosylases and AP-endonucleases in rat organotypic hippocampal slice cultures exposed to oxygen and glucose deprivation (OGD) - an in vitro model of stroke. Under basal conditions, AP-endonuclease activity and base removal of ethenoadenine and 8-oxoguanine (8-oxoG) were higher (by approximately 20-35 %) in CA3/fascia dentata (FD) than in CA1. Base removal of uracil did not differ between the two hippocampal regions, while removal of 5-hydroxyuracil (5-OHU) was slightly less efficient in CA3/FD than in CA1. Analyses performed immediately after 30 min of OGD revealed a decreased AP-endonuclease activity (by approximately 20%) in CA1 as well as CA3/FD, and an increased ethenoadenine activity (by approximately 25%) in CA1. Activities for 8-oxoG, 5-OHU and uracil showed no significant changes at this time point. At 8h after OGD, none of the enzyme activities differed from control values. Real-time RT-PCR showed that transcription of DNA glycosylases, including Ogg1, Nth1, Ung, Aag, Neil1 and Neil2 were not changed in response to OGD treatment (t=0 h). The hippocampal expression of Neil2 was low compared with the other DNA glycosylases. These data indicate that CA1 has a lower capacity than CA3/FD for removal of base lesions under basal conditions. The relatively low capacity for BER in basal conditions and the apparent failure to upregulate repair of oxidative damage after OGD might contribute to the high vulnerability of CA1 to ischemic injury.
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PMID:Base excision repair activities in organotypic hippocampal slice cultures exposed to oxygen and glucose deprivation. 1840 15


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