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Biomedical subjects

J Wu

Publications and source records attributed to J Wu.

At least 631 records · Page 35Linked to original sources

A reliable method for the simultaneous identification of H pylori and gastric metaplasia in the duodenum.

While an association of Helicobacter pylori infection with duodenal mucosa gastric metaplasia has been described, the details and extent of the interaction are lacking. One of the limiting factors has been the lack of a staining technique that allows simultaneous visualisation of the bacteria and gastric metaplasia in the duodenum. This report describes a new stain that allows the simultaneous visualisation of duodenal gastric metaplasia and H pylori and compares the new stain with the component stains.

Duodenum↗

Modified Genta triple stain for identifying Helicobacter pylori.

AIM: To evaluate whether lead nitrate could replace uranyl nitrate in the Genta stain for H pylori without sacrificing the advantages of the triple stain (Steiner silver impregnation combined with Alcian blue and haematoxylin/eosin (H&E)). METHODS: A comparison was made in 16 specimens between the original triple stain and the revised version. One pathologist evaluated all sections. RESULTS: Direct substitution of lead nitrate for uranium nitrate produced well stained organisms without interfering with H&E or Alcian blue staining. No difference was found in the ability to identify bacteria in 11 cases with H pylori density of 1 or 2 (on a scale of 0 to 5). CONCLUSIONS: The potential chemical and radiological hazards associated with uranium nitrate can be eliminated by using lead nitrate without sacrificing the advantages obtained by using the triple stain.

Coloring Agents↗

Cyclosporin-induced dyslipoproteinemia is associated with selective activation of SREBP-2.

The use of cyclosporin A has contributed greatly to the success of organ transplantation. However, cyclosporin-associated side effects of hypertension, nephrotoxicity, and dyslipoproteinemia have tempered these benefits. Cyclosporin-induced dyslipoproteinemia may be an important risk factor for the accelerated atherosclerosis observed posttransplantation. Using a mouse model, we treated Swiss-Webster mice for 6 days with a daily dose of 20 microg/g body wt of cyclosporin and observed significant elevations of plasma cholesterol, triglyceride, and apolipoprotein B (apoB) levels relative to vehicle-alone treated control animals. Measurement of the rate of secretion of very low-density lipoprotein (VLDL) by the liver in vivo showed that cyclosporin treatment led to a significant increase in the rate of hepatic VLDL triglyceride secretion. Total apoB secretion was unaffected. Northern analysis showed that cyclosporin A treatment increased the abundance of hepatic mRNA levels for a number of key genes involved in cholesterol biosynthesis relative to vehicle-alone treated animals. Two key transcriptional factors, sterol regulatory element-binding protein (SREBP)-1 and SREBP-2, also showed differential expression; SREBP-2 expression was increased at the mRNA level, and there was an increase in the active nuclear form, whereas the mRNA and the nuclear form of SREBP-1 were reduced. These results show that the molecular mechanisms by which cyclosporin causes dyslipoproteinemia may, in part, be mediated by selective activation of SREBP-2, leading to enhanced expression of lipid metabolism genes and hepatic secretion of VLDL triglyceride.

Acetyl-CoA Carboxylase↗

Nitric oxide mediates the central sensitization of primate spinothalamic tract neurons.

Nitric oxide (NO) has been proposed to contribute to the development of hyperalgesia by activating the NO/guanosine 3',5'-cyclic monophosphate (cGMP) signal transduction pathway in the spinal cord. We have examined the effects of NO on the responses of primate spinothalamic tract (STT) neurons to peripheral cutaneous stimuli and on the sensitization of STT cells following intradermal injection of capsaicin. The NO level within the spinal dorsal horn was increased by microdialysis of a NO donor, 3-morpholinosydnonimine (SIN-1). SIN-1 enhanced the responses of STT cells to both weak and strong mechanical stimulation of the skin. This effect was preferentially on deep wide dynamic range STT neurons. The responses of none of the neurons tested to noxious heat stimuli were significantly changed when SIN-1 was administered. Intradermal injection of capsaicin increased dramatically the content of NO metabolites, NO-2/NO-3, within the dorsal horn. This effect was attenuated by pretreatment of the spinal cord with a nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). Sensitization of STT cells induced by intradermal injection of capsaicin was also prevented by pretreatment of the dorsal horn with the NOS inhibitors, L-NAME or 7-nitroindazole. Blockade of NOS did not significantly affect the responses of STT cells to peripheral stimulation in the absence of capsaicin injection. The data suggest that NO contributes to the development and maintenance of central sensitization of STT cells and the resultant mechanical hyperalgesia and allodynia after peripheral tissue damage or inflammation. NO seems to play little role in signaling peripheral stimuli under physiological conditions.

Animals↗

Nitric oxide-mediated spinal disinhibition contributes to the sensitization of primate spinothalamic tract neurons.

This study concentrated on whether an increase in spinal nitric oxide (NO) diminishes inhibition of spinothalamic tract (STT) cells induced by activating the periaqueductal gray (PAG) or spinal glycinergic and GABAergic receptors, thus contributing to the sensitization of STT neurons. A reduction in inhibition of the responses to cutaneous mechanical stimuli induced by PAG stimulation was seen in wide dynamic range (WDR) STT cells located in the deep layers of the dorsal horn when these neurons were sensitized during administration of a NO donor, 3-morpholinosydnonimine (SIN-1), into the dorsal horn by microdialysis. In contrast, PAG-induced inhibition of the responses of high-threshold (HT) and superficial WDR STT cells was not significantly changed by spinal infusion of SIN-1. A reduction in PAG inhibition when STT cells were sensitized after intradermal injection of capsaicin could be nearly completely blocked by pretreatment of the dorsal horn with a NO synthase inhibitor, 7-nitroindazole. Moreover, spinal inhibition of nociceptive activity of deep WDR STT neurons elicited by iontophoretic release of glycine and GABA agonists was attenuated by administration of SIN-1. This change paralleled the change in PAG-induced inhibition. However, the inhibition of HT and superficial WDR cells induced by glycine and GABA release did not show a significant change when SIN-1 was administered spinally. Combined with our recent results, these data show that the effectiveness of spinal inhibition can be reduced by the NO/cGMP pathway. Thus disinhibition may constitute one mechanism underlying central sensitization.

Animals↗

Inhibition of primate spinothalamic tract neurons by spinal glycine and GABA is modulated by guanosine 3',5'-cyclic monophosphate.

Our recent work has suggested that the nitric oxide/guanosine 3', 5'-cyclic monophosphate (NO/cGMP) signal transduction system contributes to central sensitization of spinothalamic tract (STT) neurons in part by influencing the descending inhibition of nociception resulting from stimulation in the periaqueductal gray. This study was designed to examine further whether activation of the NO/cGMP cascade reduces the inhibition of the activity of STT neurons mediated by spinal inhibitory amino acid (IAA) receptors. Responses of STT cells to noxious cutaneous stimuli were inhibited by iontophoresis of glycine and GABA agonists in anesthetized monkeys. Administration of 8-bromoguanosine-3',5'-cyclophosphate sodium (8-bromo-cGMP), a membrane permeable analogue of cGMP, either by microdialysis or by iontophoresis reduced significantly the IAA-induced inhibition of wide dynamic range (WDR) STT cells in the deep layers of the dorsal horn. The reduction in inhibition lasted for up to 1-1.5 h after the cessation of drug infusion. In contrast, IAA-induced inhibition of WDR STT cells in the superficial dorsal horn and high-threshold (HT) cells in superficial or deep layers was not significantly changed during 8-bromo-cGMP infusion. Iontophoresis of 8-bromo-cGMP onto STT cells produced the same actions as produced by microdialysis of this agent, but the effect was not as long-lasting nor as potent. Finally, an attenuation of the IAA receptor-mediated inhibition of STT cells produced by iontophoretic release of a NO donor, 3-morpholinosydnonimine, could be blocked by pretreatment of the spinal cord with a guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. These results suggest that an increased spinal cGMP level contributes to the sensitization of WDR STT neurons in the deep dorsal horn in part by down-regulating spinal IAA receptors. However, no evidence is provided in this study that the NO/cGMP cascade regulates IAA receptors on HT and superficial WDR neurons. Combined with the preceding studies, our data support the view that NO and cGMP function in the same signal transduction cascade and play an important role in central sensitization.

Animals↗

Dorsal root reflexes and cutaneous neurogenic inflammation after intradermal injection of capsaicin in rats.

The role of dorsal root reflexes (DRRs) in acute cutaneous neurogenic inflammation induced by intradermal injection of capsaicin (CAP) was examined in anesthetized rats. Changes in cutaneous blood flow (flare) on the plantar surface of the foot were measured using a laser Doppler flowmeter, and neurogenic edema was examined by measurements of paw thickness. To implicate DRRs in neurogenic inflammation after CAP injection, the ipsilateral sciatic and femoral nerves were sectioned, dorsal rhizotomies were performed at L(3-)-S(1), and antagonists of GABA or excitatory amino acid receptors were administered intrathecally. Intradermal injection of CAP evoked a flare response that was largest at 15-20 mm from the injection site and that spread >30 mm. Acute transection of the sciatic and femoral nerves or dorsal rhizotomies nearly completely abolished the blood flow changes 15-20 mm from the CAP injection site, although there was only a minimal effect on blood flow near the injection site. These procedures also significantly reduced neurogenic edema. Intrathecal bicuculline, 6-cyano-7-nitroquinoxaline-2,3-dione, (CNQX) or D(-)-2-amino-7-phosphonoheptanoic acid (AP7), but not phaclofen, also reduced dramatically the increases in blood flow 15-20 mm from the CAP injection site, but had only a minimal effect on blood flow near the injection site. Neurogenic edema was reduced by the same agents that reduced blood flow. Multiunit DRRs recorded from the central stumps of cut dorsal rootlets in the lumbar spinal cord were enhanced after CAP injection. This enhanced DRR activity could be reduced significantly by posttreatment of the spinal cord with bicuculline, CNQX or AP7, but not phaclofen. It is concluded that peripheral cutaneous inflammation induced by intradermal injection of CAP involves central nervous mechanisms. DRRs play a major role in the development of neurogenic cutaneous inflammation, although a direct action of CAP on peripheral nerve terminals or the generation of axon reflexes also may contribute to changes in the skin near the injection site.

Animals↗

Prediction of antidepressant effects of sleep deprivation by metabolic rates in the ventral anterior cingulate and medial prefrontal cortex.

OBJECTIVE: Sleep deprivation has been shown to have an antidepressant benefit in a subgroup of depressed patients. Functional imaging studies by the authors and others have suggested that patients with elevated metabolic rates in the anterior cingulate gyrus at baseline are more likely to respond to either sleep deprivation or antidepressant medications than patients with normal metabolic rates. The authors extend their earlier work in a larger group of patients and explore additional brain areas with statistical probability mapping. METHOD: Thirty-six patients with unipolar depression and 26 normal volunteers were studied with positron emission tomography before and after sleep deprivation. Response to sleep deprivation was defined as a 40% or larger decrease in total scores on the Hamilton Depression Rating Scale. RESULTS: One-third of the depressed patients had a significant response to sleep deprivation. Responders had higher relative metabolic rates in the medial prefrontal cortex, ventral anterior cingulate, and posterior subcallosal gyrus at baseline than depressed patients who did not respond to sleep deprivation and normal volunteers. Lower Hamilton depression scores correlated significantly with lower metabolic rates in the left medial prefrontal cortex. After sleep deprivation, significant decreases in metabolic rates occurred in the medial prefrontal cortex and frontal pole in the patients who responded positively to sleep deprivation. CONCLUSIONS: High pretreatment metabolic rates and decreases in metabolic rates after treatment in the medial prefrontal cortex may characterize a subgroup of depressed patients who improve following sleep deprivation and, perhaps, other antidepressant treatments.

Adolescent↗

Proximodistal axis formation in the Drosophila leg: subdivision into proximal and distal domains by Homothorax and Distal-less.

The developing legs of Drosophila are subdivided into proximal and distal domains by the activity of the homeodomain proteins Homothorax (Hth) and Distal-less (Dll). The expression domains of Dll and Hth are initially reciprocal. Wingless and Dpp define both domains by activating Dll and by repressing Hth in the distal region of the disc. Wg and Dpp do not act through Dll to repress Hth. Hth functions to reduce the sensitivity of proximal cells to Wg and Dpp. This serves to limit the effective range of these signals in regulating later-acting genes such as Dac. We present evidence that proximal and distal cells tend to sort-out from one another. Cells forced to express Hth are unable to mix with distal cells. Likewise, cells forced to express Dll are unable to mix with proximal cells. Clones of cells unable to express Dll in the distal region sort-out from the disc. Clones of cells unable to express Hth lose the specialized population of cells at the interface between proximal and distal territories and cause fusion between body wall and leg segments. These observations suggest that sorting-out behavior of Hth- and Dll-expressing cells contributes to subdivision of the leg into proximal and distal domains.

Animals↗

Distinct roles for astrocyte alphavbeta5 and alphavbeta8 integrins in adhesion and migration.

The alphav integrins are likely to be an important group of molecules for regulating astrocyte behaviour within the central nervous system. Together with their ligand vitronectin, they are expressed by astrocytes in vivo and are further upregulated during neurological disease. Here we have characterised the expression of alphav integrins on primary astrocytes from both rat and mouse, and shown that they express just two members, alphavbeta5 and alphavbeta8. By using RGD peptides and function-blocking antibodies against the beta1 integrins and alphavbeta5, we find that both alphavbeta5 and alphavbeta8 can act as functional receptors for vitronectin. However, while alphavbeta5 is largely responsible for astrocyte adhesion to vitronectin this integrin appears to play no role in migration on vitronectin, with alphavbeta8 playing the dominant role in promoting migration on this substrate. beta1 integrins are not involved in mediating interactions between astrocytes and vitronectin. These results were confirmed in experiments with astrocytes derived from mice in which the beta5 gene had been deleted by homologous recombination. beta5 null astrocytes attached to vitronectin at a reduced rate, but showed no defect in migration on vitronectin relative to wild-type astrocytes. These data provide the first evidence that alphavbeta8 regulates migration and show that astrocyte alphavbeta5 and alphavbeta8 integrins have distinct functions.

Animals↗

Assessment of various carbon sources and nutrient feeding strategies for Panax ginseng cell culture.

Ginseng (root of Panax ginseng C. A. Meyer) cells were cultivated on medium supplemented with various carbohydrates including sucrose, glucose, and fructose, at initial concentrations ranging from 10 to 110 g/L. Sucrose was shown to be the superior carbon source to the monosaccharides for ginseng cell growth and the optimal concentration was between 30 and 50 g/L. An increase in the initial concentration within this range increased the maximum cell density and growth index significantly, whereas much higher concentrations inhibited cell growth. Feeding of sucrose and some other medium components during the growth (fed-batch mode) was more effective in enhancing the cell growth and biomass productivity, increasing the growth index by more than 60-70% and biomass productivity by more than 50%.

Journal Article↗

Toxicity of hepatotoxins: new insights into mechanisms and therapy.

Liver injury caused by hepatotoxins, such as carbon tetrachloride (CCl4), ethanol, and acetaminophen (APAP), is characterised by varying degrees of hepatocyte degeneration and cell death via either apoptosis or necrosis. The generation of reactive intermediate metabolites from the metabolism of hepatotoxins, and the occurrence of reactive oxygen species (ROS) during the inflammatory reaction account for a variety of pathophysiologic pathways leading to cell death, such as covalent binding, disordered cytosolic calcium homeostasis, glutathione (GSH) depletion, onset of mitochondrial permeability transition (MPT) and associated lipid peroxidation. The metabolism of hepatotoxins by cytochrome P-450 enzyme subtypes is a key step of the intoxication; therefore, enzyme inhibitors are shown to minimise the hepatotoxin-associated liver damage. Understanding the function of transcription factors, such as nuclear factor kappaB (NF-kappaB) in acute liver injury, may provide some answers as to the molecular mechanisms of toxic insults. Moreover, substantial evidence exists that MPT is involved in ROS-associated hepatocellular injury and new findings offer a novel therapeutic approach to attenuate cell damage by blocking the onset of MPT. Thus, oxidant stress and lipid peroxidation are crucial elements leading to hepatotoxin-associated liver injury. In addition to specific treatment for a given hepatotoxin, the general strategy for prevention and treatment of the damage includes reducing the production of reactive metabolites of the hepatotoxins, using anti-oxidative agents, and selectively targeting therapeutics to Kupffer cells or hepatocytes for on-going processes, which play a role in mediating a second phase of the injury.

Journal Article↗

Portable CT: assessing thoracic disease in the intensive care unit.

OBJECTIVE: The objective of this study was to assess the usefulness of a portable CT scanner to evaluate and treat thoracic disease in patients in the intensive care unit. MATERIALS AND METHODS: Fourteen patients who were being treated in the intensive care unit underwent 20 portable CT scans. Twice a CT scan was obtained to guide an interventional chest procedure. The remaining 18 scans were assessed for findings not evident on portable chest radiography and for findings that altered treatment. Image quality was judged in comparison with fixed CT scans. RESULTS: Unsuspected abnormalities, most relating to the pleura or chest wall, were found in 13 of the 17 available portable CT scans. Treatment was affected in four (25%) of the 16 cases in which medical records were available for review. Two interventional procedures were performed successfully using portable CT guidance. Scan quality was judged to be comparable with that of fixed CT for mediastinal windows and somewhat inferior for lung windows. CONCLUSION: Portable CT gives images of diagnostic quality and allows confident guidance during interventional procedures in critically ill patients who therefore need not leave the intensive care unit environment.

Adult↗

Effect of cavosurface angle on dentin cavity adaptation of resin composites.

The effect of the cavosurface angle of dentin cavities prepared in extracted human molars on the cavity adaptation of a resin composite was evaluated by measuring the gap width between the resin composite and the dentin cavity wall. Cavities with cavosurface angles of 90 degrees, 120 degrees, 135 degrees, or 150 degrees were pretreated with one of two commercial dentin bonding systems or an experimental dentin bonding system. The contraction gap width was measured at both the cavity margin and the section cavity using a light microscope. Complete cavity adaptation was obtained with pretreatment of the experimental groups regardless of the cavosurface angle. The contraction gap observed at the cavity margin was prevented with the two commercial dentin bonding systems when the cavosurface angle was increased to 150 degrees. A high correlation was observed between the contraction gap width and the proportion of the free surface to the adhesive surface of the resin composite restoration.

Composite Resins↗

[A preliminary study of human Y chromosome specific short tandem repeat loci].

OBJECTIVE: To understand the allele structure and reveal genetic polymorphism of Y chromosome specific short tandem repeat (Y-specific STR) loci in Chinese Han population. METHODS: The authors used a set of five Y-specific STR loci which were tetrameric tandem repeat loci chosen from the Genome Database. EDTA-blood specimens were collected from the unrelated individuals. DNA was extracted by Chelex method and amplified by the polymerase chain reaction (PCR). The PCR products were analyzed using both the PAGE horizontal electrophoresis with discontinuous buffer system and the automated fluorescence detection approach. RESULTS: The authors observed that the alleles at the five Y-specific STR loci were composed of some complex repeat structures. They successfully prepared a set of human allele ladders for the typing of the five Y-specific STRs and demonstrated the polymorphisms at the five Y-specific STR loci in Chinese Han population. CONCLUSION: Y-specific STRs are good genetic markers for the purpose of analysis of genetic relationship between populations. This preliminary study not only reveals allele frequencies and haplotype distribution of Y-specific STR in Chinese Han population, but also indicates a reference population for detecting male migration events and for reconstructing paternal history.

Chromosome Mapping↗

[Polymorphisms of five short tandem repeat systems in Chinese Han population in Chengdu].

OBJECTIVE: To get preliminary genotype and allele frequency distributions of D6S366, D6S477, D12S375, D12S391 and PLA2A loci in Chinese Han population in Chengdu area and to validate more short Tandem repeat (STR) systems for forensic application. METHODS: The polymerase chain reaction (PCR) was used. Five STR systems (D6S366, D6S477, D12S375, D12S391 and PLA2A) were amplified on DNA samples, which were extracted from 108 unrelated individuals EDTA-blood by Phenol/Chloroform method. The PCR products were analyzed by PAG vertical electrophoresis. RESULTS: Seven alleles were found at D6S366 locus, nine alleles at D6S477 locus, five alleles at D12S375 locus, nine alleles at D12S391 locus and seven alleles at PLA2A locus. No deviations from Hardy-Weinberg equilibrium were observed. The heterozygosities observed were 0.69, 0.78, 0.81, 0.68 and 0.79 for D6S366, D6S477, D12S375, D12S391 and PLA2A respectively. The chances of exclusion were 0.3621, 0.6004, 0.4581, 0.7014 and 0.5589 and the discriminating powers were 0.79, 0.93, 0.86, 0.96 and 0.91. CONCLUSION: All of the five loci in this study were useful markers for individual identification and paternity test and for genetics purposes.

Alleles↗

Known mutations of apoB account for only a small minority of hypobetalipoproteinemia.

Low LDL cholesterol and apoB levels in plasma cosegregate with mutations of apoB in some kindreds with familial hypobetalipoproteinemia. Approximately 35 apoB mutations, many specifying apoB truncations, have been described. Based on the centile nomenclature where the full-length nature apoB consisting of 4536 amino acids is designated as apoB-100, only those truncations of apoB >25% of normal length are detectable in plasma. Previously, we reported on five unrelated kindreds with familial hypobetalipoproteinemia in whom although no apoB truncations were detectable in plasma, low apoB levels were nevertheless linked to the apoB gene. In one of those kindreds, we reported a donor splice site mutation in intron 5 (specifying apoB- 4). We now describe a nonsense mutation in exon 10 (apoB-9) in two of the other unrelated families. Both the apoB-4 and apoB-9 mutations have been reported by others in unrelated families. Recurrent mutations of apoB-40 and apoB-55 also have been reported, suggesting that recurrent mutations of apoB may account for an appreciable proportion of familial hypobetalipoproteinemia kindreds. To test this hypothesis, we searched for four apoB mutations whose products are not detected in plasma including the apoB-4, apoB-9, and two other previously reported mutations in exons 21 and 25. We studied three groups with plasma cholesterols <130 mg/dl in whom no apoB truncations were detected in plasma: a) 28 FHBL probands from St. Louis, b) 151 individual St. Louisians, and c) 28 individual Sicilians. One subject from the 28 kindreds and two subjects among 151 hypobeta individuals from St. Louis harbored the exon 10 mutation. None of the other mutations were detected. Thus, among hypobeta lipoproteinemic subjects without any detectable apoB truncations in plasma, <5% had an apoB truncation-producing mutation. As only about 0.5% of hypobeta lipoproteinemic subjects have plasma-detectable apoB truncations, our data suggest that the known apoB truncations account for only a small proportion of hypocholesterolemia.

Apolipoproteins B↗

[Genetic polymorphism at FES locus in Chinese and German populations].

OBJECTIVE: The aim of this study on the genetic polymorphism at FES locus was to know whether there is genetic relationship between Chinese and German populations. METHODS: EDTA-blood specimens were collected from 311 healthy unrelated Han individuals in Jilin, Chengdu and Guangzhou in China and from 123 healthy unrelated individuals in Germany. The DNA samples were extracted using Chelex method and amplified by PCR technique. The PAGE horizontal electrophoresis was used for typing the PCR product.DNA sequences were analyzed by ALF. RESULTS: There were nine alleles at FES locus in the Chinese population. The allele frequencies were FES*6,0-0. 0051; FES *8,0-0.0042; FES*9,0.0083-0.0202; FES*10,0.0202-0.0604; FES*11,0.4066-0.5101; FES*12,0.2424-0.3099;FES*13, 0.1860-0.2198; FES*14,0.0041-0.0165; and FES*15,0-0.0050, respectively. In the German population, a variation in 5 flanking region and nine alleles at FES locus were noted. The allele frequencies were FES*8,0.0120; FES*10a,0.02317; FES*10,0.0407; FES*11a,0.0122; FES*11,0.4146; FES*12a, 0.0041; FES*12, 0.2357; FES*13, 0.0447; and FES*14, 0.0041, respectively. The results of test for Hardy-Weinberg equilibrium showed that the genotype distributions observed in the populations were correspondent with the expected. CONCLUSION: There is a remarkable difference in the distribution of allele frequencies at FES locus between Chinese and German populations.

Alleles↗