Biomedical subjects

Y Y He

Publications and source records attributed to Y Y He.

At least 37 records · Page 2Linked to original sources

PubMed1997

A cross-cultural validation of coping strategies and their associations with caregiving distress.

Coping strategies were compared among family caregivers of Alzheimer's disease patients in Shanghai, China (n = 110) and San Diego, California (n = 139). Four coping factors were reliably consistent in both samples, supporting their widespread relevance to life adversity; behavioral confronting, behavioral distancing/social support, cognitive confronting, and cognitive distancing. Shanghai and San Diego caregivers endorsed similar rates of coping, but Shanghai caregivers reported fewer symptoms of depression and anxiety. Although coping strategies were similar, cultural ideals promoting family interdependence, veneration of elderly family members, and acceptance of traditional family roles may have reduced the psychological impacts of caregiving in the Shanghai sample.

Adaptation, Psychological↗

PubMed1997

Multiple-dose mannitol reduces brain water content in a rat model of cortical infarction.

BACKGROUND AND PURPOSE: Repeated use of mannitol in the setting of ischemic infarction is a controversial and poorly defined therapeutic intervention. The purpose of this study was to examine the effects of repeated mannitol infusions on brain water content and tissue pressure in a well-defined rat model of focal ischemic stroke. METHODS: Mannitol infusions (0.5, 1.5, or 2.5 g/kg) were given by intravenous bolus 4 or 24 hours after 90-minute transient cortical ischemia in the territory of the right middle cerebral artery in rats and every 4 hours thereafter for a total of 24 hours. Fluid replacement was limited to 0.5 mL i.v. isotonic saline administered immediately after each mannitol dose. Control rats received 0.5 mL i.v. saline at the same intervals and were otherwise under ad libitum conditions. Water contents (percent H2O) of whole hemispheres and of cortical biopsies were measured with the wet-dry method, and blood samples were analyzed for plasma osmolality and chemistries. In a subgroup of rats, tissue pressure was also measured within the hemisphere ipsilateral to the infarct. RESULTS: Repeated mannitol infusions resulted in a dose-dependent increase in plasma osmolality and a dose-dependent decrease in the percent H2O of the ischemic middle cerebral artery cortex and ipsilateral hemisphere. In contrast, percent H2O of the contralateral cortex and hemisphere was significantly decreased only in the groups given the highest dose of mannitol (2.5 g/kg). Mannitol infusions at a dose of 1.5 g/kg begun 24 hours after reperfusion were also associated with a significant reduction of tissue pressure. CONCLUSIONS: In a rat model of ischemic cortical infarction, repeated mannitol infusions resulted primarily in a decrease in the percent H2O of the infarct and ipsilateral hemisphere, as well as decreased tissue pressure.

Animals↗

PubMed1996

The role of zinc in selective neuronal death after transient global cerebral ischemia.

Zinc is present in presynaptic nerve terminals throughout the mammalian central nervous system and likely serves as an endogenous signaling substance. However, excessive exposure to extracellular zinc can damage central neurons. After transient forebrain ischemia in rats, chelatable zinc accumulated specifically in degenerating neurons in the hippocampal hilus and CA1, as well as in the cerebral cortex, thalamus, striatum, and amygdala. This accumulation preceded neurodegeneration, which could be prevented by the intraventricular injection of a zinc chelating agent. The toxic influx of zinc may be a key mechanism underlying selective neuronal death after transient global ischemic insults.

Aminoquinolines↗

PubMed1996

Increased expression of the neurofibromatosis 1 (NF1) gene product, neurofibromin, in astrocytes in response to cerebral ischemia.

Tumor suppressor genes encode proteins involved in growth regulation in differentiating and proliferating cells. Previous work from our laboratory has demonstrated that the neurofibromatosis 1 (NF1) tumor suppressor gene is dramatically upregulated in astrocytes stimulated with dibutyryl cyclic AMP and proinflammatory cytokines. To explore the possibility that the NF1 gene product, neurofibromin, plays a role in the reactive gliosis seen in response to cerebral ischemia, expression of NF1 was examined in both focal and global models of rat cerebral ischemia. In this report, we demonstrate the increased expression of both neurofibromin and glial fibrillary acidic protein (GFAP) in astrocytes surrounding areas of focal ischemia. Similar increases in neurofibromin and GFAP immunoreactivity were also observed in reactive astrocytes in the hippocampal region in a global model of ischemia. These results suggest a novel role for the NF1 tumor suppressor gene in growth regulatory pathways involved in cellular remodeling and in response to injury.

Animals↗

PubMed1996

In vitro evolution of the DNA binding sites of Escherichia coli methionine repressor, MetJ.

The SELEX procedure was used to study the recognition between the E. coli methionine repressor (MetJ) and its DNA binding sites. DNA ligands with high affinity for either the holo-repressor or apo-repressor were isolated from a pool of molecules randomized over 20 base-pairs. Among 90 DNA ligands selected by holo-repressor binding, roughly 90% contain variations of two tandem, perfect eight base-pair Met-boxes, which are the consensus deduced from natural met operators. Base-pairs that are important, for specific interactions with the protein are highly conserved. The data also reveal the importance of the non-contacted operator base-pairs in facilitating the conformational changes in the operator which must occur for repressor binding. There are also effects due to the sequences of the base-pairs immediately flanking the operator site. DNA ligands selected by apo-repressor share a very similar, but not identical, consensus with that selected by holo-repressor, suggesting that the corepressor does not greatly alter the specificity of repressor binding.

Bacterial Proteins↗

PubMed1996

Automated measurement of infarct size with scanned images of triphenyltetrazolium chloride-stained rat brains.

BACKGROUND AND PURPOSE: The extent of brain infarction after local cerebral ischemia is frequently assessed with the mitochondrial activity indicator 2,3,5-triphenyltetrazolium chloride (TTC). We describe an automated procedure for analysis of infarct size in TTC-stained rat brains. METHODS: Rats were subjected to middle cerebral artery occlusion and killed after 24 to 36 hours, and their brains were processed for TTC staining. Digital images of coronal sections from these brains (n > 50) were acquired with a desktop color scanner. The resulting images were divided into red, blue, and green component images. Total brain and infarct areas were automatically determined on the basis of total pixel intensity and area after segmentation of the red and green images, respectively. Automated measurements were compared with those made with a video camera-based image acquisition system that required manual tracing of lesion boundaries. RESULTS: The spatial resolution of scanned brain images (approximately equal to 200 microns) was comparable to that of the camera-based system and provided sufficient detail to recognize infarct boundaries and neuroanatomical features. Scanner-based acquisition and analysis were faster than with the camera-based method. The green component image accurately distinguished infarcted from normal brain, and the red component image represented total brain dimensions. Infarct measurements obtained by the automated method correlated closely with those from conventional apparatus (R2 = .89, P < .001). Intraobserver reliability with the automated method (R2 = 1.00) was higher than with the conventional method (R2 = .77). CONCLUSIONS: Infarct size after middle cerebral artery occlusion in the rat can be rapidly and reproducibly assessed with inexpensive scanning equipment and automated image analysis of TTC-stained brains.

Animals↗

PubMed1995

Inositol trisphosphate, polyphosphoinositide turnover, and high-energy metabolites in focal cerebral ischemia and reperfusion.

BACKGROUND AND PURPOSE: Although the signaling pathway involving polyphosphoinositide (poly-PI) hydrolysis and release of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] is an important mechanism for regulation of neuronal calcium homeostasis, the effect of cerebral ischemia-reperfusion on this calcium signaling pathway is not well understood. Because activity of this pathway is dependent on availability of ATP, this study is aimed at examining the poly-PI signaling pathway and high-energy metabolites in a rat stroke model. METHODS: Focal cerebral ischemia in rats was induced by temporary occlusion of the right middle cerebral artery and both common carotid arteries. Levels of Ins(1,4,5)P3 were determined by use of the radioreceptor binding assay. Poly-PI turnover in rat cortex was assessed with an in vivo protocol involving intracerebral injection of [3H] inositol and systemic administration of lithium. High-energy metabolites (ATP, ADP, and AMP) were analyzed by high-performance liquid chromatography. RESULTS: Ischemia induced an increase in poly-PI turnover in the right middle cerebral artery cortex, but reperfusion led to a decline in this signaling activity. However, Ins(1,4,5)P3 levels decreased during ischemia, and these levels were not restored if ischemic insults were longer than 30 minutes. ATP levels decreased to 26% of control during ischemia and recovered to 80% of control during the initial 4 hours of reperfusion; these changes were followed by a second phase of decline. CONCLUSIONS: Results show an important relationship between ischemia-induced depletion of high-energy metabolites and poly-PI signaling activity. However, the uncoupling between Ins(1,4,5)P3 and ATP during reperfusion after severe ischemia suggests that metabolism of Ins(1,4,5)P3 is more stringently regulated than ATP.

Adenosine Diphosphate↗

PubMed1995

Detection of free radicals by microdialysis/spin trapping EPR following focal cerebral ischemia-reperfusion and a cautionary note on the stability of 5,5-dimethyl-1-pyrroline N-oxide (DMPO).

We have examined free radical production in a rat model of focal cerebral ischemia using microdialysis coupled with EPR analysis. A microdialysis probe was inserted 2 mm into the cerebral cortex, supplied by the right middle cerebral artery (MCA), and after a 2-hour washout period with artificial cerebral spinal fluid (ACSF), the perfusate solution was changed to ACSF containing the spin trapping agent, 5,5-dimethyl-1-pyrroline N-oxide (DMPO). No free radicals were detected by DMPO during the pre-ischemia period. Both common carotid arteries and the right MCA were then ligated for 90 minutes. Microdialysate collected every 15 min during the ischemic period demonstrated predominantly superoxide or peroxyl radical production. After release of the occlusive sutures, hydroxyl radical became apparent initially, then thiyl and carbon centered radicals appeared later in samples collected every 15 min for two hours following cortical reperfusion. Careful studies on the purification and stability of DMPO solution were performed to circumvent artifacts and spurious signals.

Animals↗

PubMed1994

The Met repressor-operator complex: DNA recognition by beta-strands.

The crystal structure of the E. coli met repressor in complex with a synthetic 19-base pair oligonucleotide reveals two dimeric repressor molecules bound to adjacent sites on the DNA. The oligonucleotide contains two adjacent repeats of an 8-mer known as a met-box, which represents the consensus of the met operator sites. Each met repressor dimer is centered on a met box and interacts with the adjacent dimer through antiparallel alpha-helices, which explained the observed cooperative nature of the binding. DNA binding takes place through the insertion of a beta-ribbon into the major groove of B-form DNA, representing a novel DNA binding motif. Sequence specificity arises from direct interactions between side chains of the beta-strands and the edges of the bases in the major groove. The local DNA conformation confers additional specificity through interactions between protein and the phosphate backbone. The repressor is activated through binding of S-adenosyl methionine (SAM), the corepressor, to the face opposite to that used for DNA binding. The lack of significant conformational change upon SAM binding, together with electrostatic calculations, suggests that DNA binding enhancement occurs through long-range electrostatic interactions.

Bacterial Proteins↗

PubMed1994

Suppression of ischemia-induced fos expression and AP-1 activity by an antisense oligodeoxynucleotide to c-fos mRNA.

Activation of c-fos, an immediate early gene, and the subsequent expression of the Fos protein have been noted following focal cerebral ischemia. Fos and Jun form a heterodimer as activator protein 1 (AP-1), which transregulates the expression of several genes. To study the postischemic events related to c-fos expression, we suppressed the expression of c-fos by intraventricular infusion of an antisense oligodeoxynucleotide (anti-rncfosr115) of c-fos mRNA. The effectiveness of anti-rncfosr115 was confirmed first by its capability to block in vitro c-fos mRNA translation. In vivo, after intraventricular infusion of 32P-labeled anti-rncfosr115, the oligodeoxynucleotide was internalized within 6 hours and detectable also in the nucleic acids fraction up to 41 hours. Treatment of the recovered nucleic acids with RNase H separated the labeled oligodeoxynucleotide from the nucleic acid fraction, indicating an association of the antisense oligodeoxynucleotide and cellular RNA after uptake. When focal cerebral ischemia was induced 16 hours after the infusion of anti-rncfosr115, the postischemic increase in Fos expression and AP-1 binding activity were suppressed. Specificity of the effect of anti-rncfosr115 was suggested by its failure to suppress the DNA binding activity of nuclear cyclic AMP response elements. These results support the hypothesis that increased AP-1 binding activity following focal cerebral ischemia is dependent on Fos expression and can be inhibited in vivo by antisense c-fos oligodeoxynucleotides.

Animals↗

PubMed1993

Effects of focal cerebral ischemia on expression and activity of inositol 1,4,5-trisphosphate 3-kinase in rat cortex.

Results from this study clearly indicate that Ins(1,4,5)P3 3-kinase is a target enzyme of cerebral ischemia insult. This enzyme is responsible for removal of Ins(1,4,5)P3 which, in turn, plays an important role in the maintenance of intracellular Ca2+ homeostasis. Not only did a time-dependent decrease in enzyme activity occur due to the focal cerebral ischemic insult, but there was also a second phase for the decline in enzyme activity around 6 h after the insult. Examination of the mRNA for the 3-kinase in frozen brain sections suggested an increase in message at a time (around 8 h) prior to development of tissue infarct. Since the initial decline in enzyme activity during ligation correlated well with the time for development of an infarct, assay of this enzyme could be used as a biochemical marker of cerebral ischemic insult.

Animals↗

PubMed1993

Expression of c-fos and c-jun family genes after focal cerebral ischemia.

The expression of the protooncogenes, c-fos, jun B, c-jun, and jun D was investigated in a rat focal cerebral ischemia model by Northern analysis and in situ hybridization. Severe ischemia (reduction of regional blood flow by 88-92%) in this model is confined to cerebral cortex irrigated by the right middle cerebral artery. Ischemia for 30 minutes, which caused only slight cortical damage (infarct size, < 10 mm3), induced both jun B and c-fos mRNAs exclusively in the right cerebral cortex. Ischemia for 90 minutes, which led to large cortical infarction (infarct size, > 140 mm3), also induced the expression of these two genes in the right cerebral cortex as well as the ipsilateral hippocampus. The latter sustained very mild ischemia (reduction of regional blood flow by 10-20%). The coinduction of jun B and c-fos expression occurred immediately after reperfusion and peaked at 60 minutes after reperfusion. The expression of c-jun was enhanced in a similar pattern, but at a much lower magnitude. In contrast, no change in jun D expression was observed. Nuclear run-on assays indicated that the increase in c-fos, jun B, and c-jun mRNA levels was due to the increase of transcription rate in these genes. Mobility shift assays showed a basal DNA binding activity of transcription factor AP-1 in the right cerebral cortex. Ischemia for 30 or 90 minutes followed by reperfusion for 4 hours resulted in a four- to sixfold increase of AP-1 binding activity. The enhanced DNA binding activity persisted for as long as 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Polyethylene glycol-conjugated superoxide dismutase in focal cerebral ischemia-reperfusion.

Generation of free radicals during reperfusion after organ ischemia has been implicated in the pathogenesis of ischemic injury. We have previously shown that a combination of intravenous polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) and catalase (PEG-CAT), at a dose of 10,000 U/kg each, is effective in reducing infarct size in a focal cerebral ischemia model in the rat. It is not clear whether PEG-SOD alone is sufficient to reduce ischemic brain injury. In this study we determined the therapeutic efficacy of PEG-SOD and its dose-response curve. In a range of 1,000-30,000 U/kg, PEG-SOD exhibited a U-shaped dose-response curve. Only 10,000 U/kg significantly reduced infarct size [control 121 +/- 12 mm3 (mean +/- SE), n = 35; PEG-SOD 95 +/- 10 mm3, n = 36, P < 0.05]. PEG-SOD at the doses tested did not have significant acute hemodynamic effects but had a tendency to improve postischemic hypotension. This beneficial effect of PEG-SOD on blood pressure did not appear to fully account for the treatment effect of PEG-SOD on infarct size. The narrow therapeutic dose range of PEG-SOD in this study and similar findings of SOD in other investigations may contribute to the inconsistent protective effects of SOD preparations in ischemia-reperfusion injury in the literature.

Animals↗

PubMed1993

Effect of brain edema on infarct volume in a focal cerebral ischemia model in rats.

BACKGROUND AND PURPOSE: Infarct volume is one of the common indexes for assessing the extent of ischemic brain injury following focal cerebral ischemia. Accuracy in the measurement of infarct volume is compounded by postischemic brain edema that may increase brain volume in the infarcted region. We evaluated the effect of brain edema on infarct volume determined by triphenyltetrazolium chloride and hematoxylin and eosin stains in a focal cerebral ischemia model in rats. METHODS: In a middle cerebral artery occlusion model in rats, infarction is confined to the cerebral cortex. The infarct was delineated by triphenyltetrazolium chloride stain and, in selected samples, by hematoxylin and eosin stain. We determined infarct size at different times after the ischemic insult (6 hours to 7 days) in relation to the evolution of brain edema by the direct measurement of infarct volume. Indirect measurement to reduce the effect of edema on infarct volume was also conducted in the same brain samples. RESULTS: Direct measurement showed that infarct volume fluctuated with the evolution of brain edema (one-way analysis of variance, p < 0.0001). Infarct volume determined by indirect measurement was independent of the extent of brain edema and remained stable from 6 hours to 3 days after ischemia. There was a good correlation between triphenyltetrazolium chloride and hematoxylin and eosin stains in delineating infarct volume with both direct and indirect measurement. CONCLUSION: Traditional direct measurement of infarct volume is associated with an overestimation of infarct volume during the development of brain edema in the first 3 days after ischemia. This artifact can be reduced with indirect measurement, which is based on noninfarcted cortex volume.

Animals↗

PubMed1993

Effects of fish oil supplementation on acute ischemic brain injury in the rat.

We studied the effects of long-term fish oil (FO) dietary supplementation on brain edema, polymorphonuclear neutrophil (PMN) infiltration, and infarct size in a rat stroke model. Rats were given regular rat chow with or without FO supplement (20% of total calories) for 7 weeks. Body weight did not differ between the two groups. In the FO group, an increase in eicosapentaenoic acid and a decrease in arachidonic acid content in hepatic phospholipids were significant in the phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine but not in the phosphoinositol fraction. Platelet activity reflected by serum thromboxane B2 levels was reduced in the FO group. Postischemic brain edema and PMN infiltration were not different between the two groups. The infarct volume was significantly greater in the FO group (controls: 96 +/- 7 mm3, n = 49; FO group: 124 +/- 6 mm3, n = 53; p = 0.0036). The greater ischemic brain injury in the FO-supplemented animals is probably related to the intraischemic hyperglycemia, which was worse in the FO group than in the control group (controls: 265 +/- 19 mg/dl, n = 14; FO group: 340 +/- 18 mg/dl, n = 16; p = 0.0079).

Animals↗

PubMed1993

[Clinical and experimental study on effects of man-shen-ling oral liquid in the treatment of 100 cases of chronic nephritis].

A new Chinese herbal preparation, Man-Shen-Ling (MSL, consisted of medicinal herbs such as Astragalus and Rehmannia) in treating 100 cases of chronic nephritis. The effective rate was 91% in comparing to 66.7% in the control group, P < 0.001. It was markedly effective for proteinuria, hematuria, improvement and recovery of renal functions, edema, anemia, anorexia etc in comparing with the control group. It showed no adverse effects on functions of liver, kidney, heart and GI tract. Animal model of chronic nephritis was established and the effects of MSL were observed. The laboratory findings and histopathological investigation on kidney revealed and confirmed that MSL has therapeutic effects on chronic nephritis. Pharmacodynamically, MSL exhibited effects of anti-allergy, its immuno-suppressive effect corresponded to that of cyclophosphamide, with diuretic, hypotensive, proteinuria eliminating, anti-inflammatory, anti-coagulatory, renal blood flow and glomerular filtration enhancing, the excretion of urea-nitrogen, potassium and sodium promoting function; in addition, it also could promote and modulate the immunity. Acute and chronic toxicity tests on animal models neither showed toxic, mutagenic, teratogenic nor carcinogenic effects. It is a new preparation of Chinese medicinal herbs in treating chronic nephritis, it is safe and effective.

Adolescent↗

PubMed1993

Expression of immediate early gene and growth factor mRNAs in a focal cerebral ischemia model in the rat.

BACKGROUND AND PURPOSE: Increased release of excitatory neurotransmitters leading to activation of signal transduction has been noted after cerebral ischemia. One of the biochemical events in the signaling processes is an alteration of gene expression. A focal cerebral ischemia-reperfusion model in the rat was used to study the postischemic alteration of selected proto-oncogene and neurotrophin gene expression. METHODS: Focal ischemia in the cerebral cortex irrigated by the right middle cerebral artery was induced by temporary occlusion of the right middle cerebral artery and both common carotid arteries for 30 or 90 minutes. Expression of selected proto-oncogenes and neurotrophin genes was studied with Northern blot analysis and in situ hybridization. RESULTS: Northern blot analysis showed that an increase in the expression of selected proto-oncogenes including c-fos, c-jun, jun B, zif/268, and nur 77 were noted 30 to 90 minutes into postischemic reperfusion. In situ hybridization revealed different regional distribution of c-fos mRNA signal under different experimental conditions. Nuclear run-on experiments showed that the increase in c-fos and jun B mRNA signals was due to an increase in the transcription rate. An increase in AP-1 binding activity in the ischemic cortex was also noted. Increased expression of brain-derived neurotrophic factor and nerve growth factor mRNAs were noted subsequent to the expression of immediate early genes in the ischemic cortex and adjacent areas in a biphasic pattern. CONCLUSIONS: Results are in agreement with the contention that increased c-fos and jun B expression leads to increased AP-1 binding activity, which in turn has been linked to the enhanced expression of neurotrophin genes.

Animals↗

PubMed1992

Probing met repressor-operator recognition in solution.

The three-dimensional crystal structure of the Escherichia coli methionine repressor, MetJ, complexed with a DNA operator fragment is described in an accompanying article. The complex exhibits several novel features of DNA-protein interaction. DNA sequence recognition is achieved largely by hydrogen-bond contacts between the bases and amino-acid side chains located on a beta-ribbon, a mode of recognition previously hypothesized on the basis of modelling of idealized beta-strands and DNA, and mutagenesis of the Salmonella phage P22 repressors Arc and Mnt. The complex comprises a pair of MetJ repressor dimers which bind to adjacent met-box sites on the DNA, and contact each other by means of a pair of antiparallel alpha-helices. Here we assess the importance of these contacts, and also of contacts that would be made between the C-helices of the protein and DNA in a previous model of the complex, by studying mutations aimed at disrupting them. The role of the carboxy-terminal helix face in operator binding was unclear, but we demonstrate that recognition of operator sequences occurs through side chains in the beta-strand motif and that dimer-dimer interactions are required for effective repression.

Base Sequence↗