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Biomedical subjects

W Ding

Publications and source records attributed to W Ding.

At least 109 records · Page 6Linked to original sources
PubMed1994

Binding of heparan sulfate glycosaminoglycan to beta-amyloid peptide: inhibition by potentially therapeutic polysulfated compounds.

Heparin sulfate proteoglycans are believed to play an important role in amyloidosis as pathologic chaperones. They bind to amyloidogenic proteins and may mediate the deposition and fibrillogenesis of amyloid at specific tissue sites. In the present study, we demonstrate that heparin sulfate glycosaminoglycan and proteoglycan both bind to the beta-amyloid peptide involved in Alzheimer's disease. The interaction of heparan sulfate proteoglycan and glycosaminoglycan can be inhibited by other sulfated compounds such as heparin, dextran sulfate and pentosan polysulfate. These polysaccharides which are currently used clinically, their derivatives or analogs may be effective as therapeutic agents to prevent or slow the progression of amyloidogenesis in Alzheimer's disease or other amyloidogenic disorders.

Amyloid beta-Peptides↗
PubMed1994

Analysis of the p16 gene (CDKN2) as a candidate for the chromosome 9p melanoma susceptibility locus.

A locus for familial melanoma, MLM, has been mapped within the same interval on chromosome 9p21 as the gene for a putative cell cycle regulator, p16INK4 (CDKN2) MTS1. This gene is homozygously deleted from many tumour cell lines including melanomas, suggesting that CDKN2 is a good candidate for MLM. We have analysed CDKN2 coding sequences in pedigrees segregating 9p melanoma susceptibility and 38 other melanoma-prone families. In only two families were potential predisposing mutations identified. No evidence was found for heterozygous deletions of CDKN2 in the germline of melanoma-prone individuals. The low frequency of potential predisposing mutations detected suggests that either the majority of mutations fall outside the CDKN2 coding sequence or that CDKN2 is not MLM.

Base Sequence↗
PubMed1994

Pyrroindomycins, novel antibiotics produced by Streptomyces rugosporus sp. LL-42D005. I. Isolation and structure determination.

Pyrroindomycins A and B were isolated from fermentations of culture LL-42D005, a strain of Streptomyces rugosporus. Pyrroindomycins possess potent antimicrobial activities against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci. Their structures have been determined by using 1- and 2-D NMR, mass spectroscopy and chemical degradations. Pyrroindomycins are the first natural products that contain the highly unsaturated pyrroloindole moiety.

Anti-Bacterial Agents↗
PubMed1994

Mechanisms of brain injury with deep hypothermic circulatory arrest and protective effects of coenzyme Q10.

Sixteen dogs, divided randomly into a control group and coenzyme Q10 group (10mg/kg, intraperitoneally before the operation), underwent deep hypothermic circulatory arrest with cardiopulmonary bypass, as is done clinically. At four time points cerebral cortex and cerebrospinal fluid specimens were collected to study free radical formation, energy metabolism, and ultrastructure. During cardiopulmonary bypass cerebral electron spin resonance spectra and malondialdehyde contents were progressively higher than before bypass, especially at the 60 minutes of circulatory arrest and 30 minutes of reperfusion (p1 < 0.01, p2 < 0.05). In the coenzyme Q10 group at the latter two time points, they had increased less than in the control group at same time points (p1 < 0.02, p2 < 0.005). Adenosine triphosphate content in the cortex during bypass decreased gradually from the prebypass level (p1 < 0.02, p2 = p3 < 0.001), while lactate in cerebrospinal fluid increased (p1 < 0.05, p2 = p3 < 0.001). In the coenzyme Q10 group, adenosine triphosphate at the latter two time points was greater than that in the control group (p1 = p2 < 0.05), while the lactate changes were not significantly different from control at each time point (all p > 0.05). Ultrastructure of the cortex was normal before bypass and almost normal during bypass, but it was obviously abnormal at 60 minutes of circulatory arrest and more seriously abnormal at 30 minutes of reperfusion. In the coenzyme Q10 group the abnormality was obviously reduced. The results suggest that oxygen-derived free radicals and abnormal energy metabolism might play critical roles in brain ischemia/reperfusion injury. Coenzyme Q10 could protect the brain by improving cerebral metabolism.

Adenosine Triphosphate↗
PubMed1994

Muscarinic receptor-stimulated expression of c-fos in neuroblastoma cells.

The intracellular signal cascade transducing muscarinic-receptor-stimulation to gene expression was investigated in human neuroblastoma SH-SY5Y cells. Naive and ethanol-exposed SH-SU5Y cells were stimulated with carbachol (CCh) and inositol 1,4-5-trisphosphate (IP3), 1,2-diacylglycerol (DAG), and c-fos mRNA levels were analyzed using a radioreceptor assay (IP3) thin-layer chromatography (DAG) and Northern blot (c-fos mRNA). Application of the muscarinic agonist CCh induced a rapid increase in (IP3), peaking within seconds after the CCh-addition. There was also an accumulation of DAG reaching maximum after 5 min of receptor-stimulation. Stimulation with CCh also induced expression of the immediate-early gene c-fos in these cells. These events were mediated via muscarinic M1 receptors and the inhibitory effects of H7, staurosporin, and RO31-7549 on the c-fos expression indicated that it was mediated via protein kinase C. Acute exposure to 100 mM ethanol inhibited the formation of IP3 and the expression of c-fos. These effects were due to an increase in the EC50 of CCh for the events. Exposure to 100 mM ethanol for 4 days caused a potentiation of these two events. The EC50 was unaffected but the maximal response was increased. These data indicate that this signal transduction system is inhibited by acute exposure to 100 mM ethanol, an effect that is compensated for after exposure to ethanol for 4 days.

Carbachol↗
PubMed1993

Binding of vascular heparan sulfate proteoglycan to Alzheimer's amyloid precursor protein is mediated in part by the N-terminal region of A4 peptide.

The exact mechanisms of deposition and accumulation of amyloid in senile plaques and in blood vessels in Alzheimer's disease remain unknown. Heparan sulfate proteoglycans may play an important role in amyloid deposition in Alzheimer's disease. Previous investigations have demonstrated high affinity binding between heparan sulfate proteoglycans and the amyloid precursor, as well as with the A4 peptide. In the current studies, a specific vascular heparan sulfate proteoglycan found in senile plaques bound with high affinity to two amyloid protein precursors (APP695 and APP770). Vascular heparan sulfate proteoglycan also bound the Alzheimer's amyloid A4 peptide, and not other amyloid protein precursor regions studied, with high affinity. Both heparan sulfate glycosaminoglycan chains and chemically deglycosylated vascular heparan sulfate proteoglycan protein core bound to A4. High affinity interactions between vascular heparan sulfate proteoglycan and the A4 peptide may play a role in the process of amyloidogenesis in Alzheimer's disease, by localizing the site of deposition of A4, protecting A4 from further proteolysis, or by promoting aggregation and fibril formation.

Alzheimer Disease↗
PubMed1993

Binding of secreted human neuroblastoma proteoglycans to the Alzheimer's amyloid A4 peptide.

Proteoglycans (PGs) may play a fundamental role in all forms of amyloidosis. In Alzheimer's disease, proteoglycans are found deposited in senile plaques and in neurofibrillary tangles. However, the cellular source of these deposited PGs and their role in amyloidosis in Alzheimer's disease is unknown. Proteoglycans were purified from conditioned medium of human neuroblastoma cells (SKNSH-SY 5Y). Two species of proteoglycans were identified by enzyme susceptibility including a heparan sulfate proteoglycan and a dermatan sulfate proteoglycan. A monoclonal antibody to the protein core of a vascular basement membrane heparan sulfate proteoglycan found in senile plaques in Alzheimer's disease cross-reacted with the proteoglycans secreted by human neuroblastoma cells. Binding between 35SO4-labelled neuroblastoma proteoglycans and the Alzheimer amyloid (A4) peptide was demonstrated by affinity chromatography. Specificity studies demonstrated that binding of human neuroblastoma proteoglycans to the amyloid peptide was specific for a heparan sulfate glycosaminoglycan, with some binding to a dermatan sulfate proteoglycan. Binding to A4 was also demonstrated by a chemically deglycosylated protein core preparation. No significant binding of neuroblastoma proteoglycans was found to two other basic peptides derived from the extracellular domain of the beta-amyloid precursor, demonstrating the specificity of proteoglycan binding to the A4 peptide. Human neuroblastoma proteoglycans may bind to the-Alzheimer amyloid A4 peptide in a region with a heparin binding consensus sequence [VHHQKL] which also contains the cleavage site of the beta-amyloid precursor protein. Neuronal proteoglycans may either regulate the secretion of the amyloid protein precursor or modify the binding of the amyloid protein precursor to other cellular adhesion molecules. Alterations in this binding may be related to the pathogenesis of amyloid deposition in Alzheimer's disease.

Alzheimer Disease↗
PubMed1993

Acute phase response in exercise. III. Neutrophil and IL-1 beta accumulation in skeletal muscle.

Nine untrained men (22-29 yr) performed 45 min of downhill running (16% incline, 70% of maximum heart rate). Needle biopsies of the vastus lateralis were performed before, 45 min after, and 5 days after exercise. Immunohistochemical staining of muscle cross sections revealed a 135% increase in muscle interleukin-1 beta (IL-1 beta) immediately after and a 250% increase (P < 0.03) 5 days after exercise. Using a rating scale (0-3) for the presence of neutrophils, light microscopic examination showed a significant accumulation of neutrophils in muscle biopsies taken 45 min after and 5 days after exercise [before: 0.5 +/- 0.2, 45 min after: 1.5 +/- 0.3 (P < 0.01), and 5 days after: 1.2 +/- 0.2 (P < 0.04)]. In addition, electron microscopic analysis showed an increase in the percentage of damaged Z-bands relative to total Z-bands [before: 4.8 +/- 3.5%, 45 min after: 32.5 +/- 8.6% (P < 0.05), and 5 days after: 14.1 +/- 3.2%]. Neutrophil accumulation was positively correlated to intracellular Z-band damage (rho = 0.66, P < 0.001). Immunohistochemical staining for IL-1 beta was related to neutrophil accumulation in muscle (rho = 0.38, P < 0.06) and to plasma creatine kinase levels (rho = 0.416, P < 0.04). These data indicate that after eccentric exercise ultrastructural damage to skeletal muscle is associated with neutrophil infiltration and muscle IL-1 beta accumulation.

Acute-Phase Reaction↗
PubMed1993

Mechanism of the preserving effect of aprotinin on platelet function and its use in cardiac surgery.

The deficiency of platelet function is the main defect of the hemostatic mechanism during cardiopulmonary bypass, which greatly exacerbates the postoperative bleeding complications. In this study, we assessed, from basic and clinical perspectives, the mechanism of relieving platelet damage by means of aprotinin. In vitro research confirmed that the addition of urokinase (40 U/ml) to platelet-rich plasma and the addition of plasmin (0.3 U/ml) to washed platelets made ristocetin-induced agglutination decline to 31.6% and 38.5% of control values, respectively. The extent of decline was positively correlated with the concentration of urokinase and plasmin. In addition, the platelet membrane glycoprotein Ib decreased to 76.4% of control value. With the addition of urokinase or plasmin to aprotinin-pretreated platelet-rich plasma or washed platelets, the changes in agglutination are not statistically significant and the decrement in glycoprotein Ib is much less marked. Further in vivo research revealed that cardiopulmonary bypass caused a decrease in plasma alpha 2-antiplasmin, indicating the fibrinolytic system activation. Meanwhile, ristocetin-induced agglutination decreased to 39.6% and platelet glycoprotein Ib decreased to 50% of preoperative values. However, with the administration of aprotinin, plasma alpha 2-antiplasmin during cardiopulmonary bypass did not change; platelet agglutination was improved, platelet glycoprotein Ib was preserved, and this consequently resulted in 46% lower blood loss after the operation. The results showed that fibrinolysis impaired platelet function, and this effect may be associated with the hydrolysis of glycoprotein Ib. Fibrinolytic activation occurred during cardiopulmonary bypass and contributed to postoperative platelet dysfunction to a great extent. Aprotinin may inhibit fibrinolysis during cardiopulmonary bypass and thus relieve the platelet damage and improve the postoperative hemostatic mechanism.

Aprotinin↗
PubMed1993

[The inhibitory effects of stimulating AC, AL, BNST and AHL on visceral pain].

We took the unit discharges of the neurons in the posterior group of thalamic nuclei (PO) caused by stimulating the great splanchnic nerve (GSN) as an indicator of visceral pain. We searched for the effects of electrical stimulating central nucleus of amygdala (AC), lateral nucleus of amygdala (AL), bed nucleus of striae terminalis (BNST) and lateral area of hypothalmus (AHL) on unit discharges of PO and the relationship among these nucleuses. The result indicated that the inhibitory effects were strongest with stimulating AC, the next was with stimulating AHL, then BNST and AL. The inhibitory percentages were 85.7% (AC), 62.9% (AHL), 53.1% (BNST) and 54.2% (AL) respectively. The inhibitory effects of stimulating AC couldn't be canceled by injecting naloxone intravenously. AC may be more important for the antinociceptive system than AL, BNST and AHL. There was no relationship between AC and BNST on the inhibition of unit discharges. The inhibitory effects of stimulating AL may be related to AC.

Amygdala↗
PubMed1992

Bovine amelogenin message heterogeneity: alternative splicing and Y-chromosomal gene transcription.

The amelogenins are the most abundant proteins in developing tooth enamel. Previous analyses have demonstrated that transcriptionally active genes encoding the proteins are located on both the bovine X and the bovine Y chromosomes. We report here the cloning and sequence analysis of the Y-chromosomal gene and corresponding cDNA. The Y-specific mRNA encodes a translation product in which a 21 amino acid domain has been deleted, relative to the X-specific amelogenin, resulting in loss of a structure tentatively described as a beta-spiral. There are also 13 single amino acid differences compared to the X-specific amelogenin. In addition, we have cloned and sequenced an X-chromosomal alternatively spliced amelogenin cDNA that encodes a 43 amino acid amelogenin primary translation product. Hydrophobicity analysis indicates that all analyzed amelogenin proteins have a mean hydrophilic character and the two peptides translated from alternatively spliced messages have significant increases in percentage of hydrophobic amino acids.

Amelogenin↗
PubMed1992

[Responses of neurons in the somato-sensory area I to noxious electric stimulation of nervus peroneus communis. The study of intracellular potentials].

Noxious electric stimulation of nervus peroneus communis (PN) results in pain. It hasn't been reported that the neurons in somatosensory area I (SI) may respond to the noxious stimulation. In this paper, using intracellular microelectrode technique, we have studied the responses of neurons in SI to noxious electric stimulating PN. 33 neurons were recorded in 18 cats. 16 neurons were related with the noxious stimulation. The responses of these neurons to noxious stimulation were mainly inhibitory postsynaptic potentials (IPSP). Some neurons responded with two IPSPs. A few neurons responded with EPSP (Excitatory postsynaptic potential)-IPSPs. The latencies of the first IPSPs were short (8.25 +/- 5.90ms) and showed that the first IPSPs might be induced by the input of A beta fiber. The latencies of the second IPSPs (In the neurons with two IPSPs) were long (60.33 +/- 6.62 ms) and showed that the second IPSPs might be induced by the input of A delta fiber. Above results show that: 1) SI neurons can respond to the noxious electric stimulation of PN. 2) The responses of SI neurons to the noxious stimulation were mainly IPSPs. 3) The second IPSPs might be related with pain.

Animals↗
PubMed1991

Structure and expression of the bovine amelogenin gene.

In order to define further the mechanisms responsible for tooth amelogenin heterogeneity, seven bovine amelogenin cDNAs were sequenced. On the basis of these sequences, five of the cDNAs could be grouped into one class which differed appreciably in sequence from the second group of two cDNAs. Two overlapping bovine genomic clones were then isolated and shown by sequencing to contain six exons encoding the entire consensus sequence of the class I cDNA. Southern blot analysis of DNA from male and female animals using class I or class II specific oligonucleotide probes suggested that the class I gene sequence was located on the X chromosome while the class II sequence was located on the Y chromosome. Therefore, these results also suggest that the genes on the X and Y chromosomes are both transcribed. Furthermore, the results are consistent with alternative splicing of the class I primary transcript as a potential mechanism for generating amelogenin heterogeneity.

Amelogenin↗
PubMedDate not supplied

Numeric flow simulation for an innovative ventricular assist system secondary impeller.

The secondary impeller of the Cleveland Clinic Foundation Innovative Ventricular Assist System heart pump is designed to pump the blood from the journal bearing through the annulus back to the discharge to rejoin the main flow. It is crucial, however, that the amount of hemolysis and potential for thrombus formation is minimized. Based on our earlier computational fluid analysis of the initial design, an improved secondary impeller has been proposed. The objective of this work was to analyze the flow with the new impeller configuration by computational fluid dynamics and to find out where in the geometry hemolysis becomes high, as well as where the potential for thrombosis exists. The present work includes: 1) visualizing the 3-dimensional flow pattern in the secondary impeller cavity, 2) investigating the tip clearance effect, and 3) estimating the shear stress distribution as a measure for blood damage caused in the secondary impeller cavity.

Blood Flow Velocity↗