Biomedical subjects

W Wu

Publications and source records attributed to W Wu.

At least 289 records · Page 16Linked to original sources

PubMed1997

Phenotypes in three Swedish families with X-linked retinitis pigmentosa caused by different mutations in the RPGR gene.

PURPOSE: To assess the clinical phenotypes in three Swedish families with X-linked retinitis pigmentosa caused by different mutations in the RPGR gene. METHODS: Three families from different parts of Sweden, including nine patients with retinitis pigmentosa and six female carriers of X-linked retinitis pigmentosa, were examined clinically. Ophthalmologic examination included kinetic perimetry with a Goldmann perimeter using standardized objects I4e and V4e, dark adaptation final thresholds with a Goldmann-Weeker adaptometer, and full-field electroretinograms. RESULTS: The clinical findings in the patients demonstrated a severe form of retinitis pigmentosa with visual handicap early in life. Patients with a microdeletion of exons 8 through 10 of the RPGR gene had a more severe phenotype compared to the patients with single base-pair mutations in the introns 10 and 13 of the RPGR gene, resulting in splicing defects. Furthermore, heterozygous carriers in these families displayed a wide spectrum of clinical features, from minor symptoms to severe visual disability. CONCLUSION: These three families show a variable clinical phenotype resulting from different mutations in the RPGR gene. A microdeletion spanning at least parts of exons 8 through 10 seems to result in a severe phenotype compared to the splice defects. Heterozygous carriers of X-linked retinitis pigmentosa with these specific RPGR genotypes also show a variability of the phenotype; carriers with the microdeletion may be severely visually handicapped.

Adolescent↗

PubMed1997

Antinociceptive effect of nifedipine and verapamil tested on rats chronically exposed to nicotine and after its withdrawal.

Antinociceptive effect of nifedipine (15 mg/kg i.p.) and verapamil (10 mg/kg s.c.) was examined in rats chronically exposed to nicotine (6 mg/kg/day via Alzet osmotic pump for 28 days) and after nicotine withdrawal. Sham operated rats served as control for testing DMSO (dimethylsulfoxide, a solvent for nifedipine), nifedipine and verapamil alone. Nociception was measured by the tail-flick technique. Nifedipine, but not verapamil, injected to control rats produced a ceiling tail-flick latency (20 sec) 30 min after the injection, lasting for 10 min. In rats exposed to chronic nicotine for 3 days, nifedipine treatment exhibited ceiling tail-flick latency within 10 min lasting for 80 min. Tested in rats exposed to nicotine for 3 weeks, nifedipine treatment produced this effect 25 min after the injection lasting for 60 min. Nicotine withdrawal abolished this effect. Verapamil did not exhibit any significant changes in tail-flick latencies. These data support our hypothesis that smoking patients treated with nifedipine could be at a potential risk in developing a high pain threshold and missing the first sign of heart attack--a chest pain.

Analgesics↗

PubMed1997

The immunosuppressive peptide of HIV-1 gp41 like human type I interferons up-regulates MHC class I expression on H9 and U937 cells.

Based on our findings that the immunosuppressive peptide (ISP, amino acids (aa) 583-599) of human immunodeficiency virus type 1 (HIV-1) gp41 shows sequence-similarity with human type I interferons (IFN-alpha and IFN-beta) and HIV-1 soluble gp41 (sgp41, aa 539-684) enhanced cell surface expression of major histocompatibility complex (MHC) class I molecule on human H9 (T cells), Raji (B cells) and U937 (monocytic cells) cells, we examined the effect of HIV-1 immunosuppressive peptide on the surface expression of MHC class I molecules on H9 and U937 cells. Flow cytometry analysis demonstrated that ISP-BSA (conjugate) could enhance MHC class I expression by about 40% on H9 cells and by about 45% on U937 cells, while monomer ISP (not conjugated) and EDCI-treated carrier protein (BSA-EDCI) did not increase the expression. By comparison, human type I interferons, IFN-alpha and IFN-beta, showed similar effects (enhanced the expression by about 40-60%) to ISP-BSA on the MHC class I expression on H9 and U937 cells. The results suggest that HIV-1 gp41 in a polymerized form by its immunosuppressive domain upregulates human MHC class I expression. The basis for this similar effect of HIV-1 gp41 and IFN-alpha and -beta, i.e. upregulation of MHC class I molecule expression, may be based on the sequence-similarity between these otherwise different molecules.

Amino Acid Sequence↗

PubMed1997

Mechanisms of adjuvancy: I--Metal oxides as adjuvants.

The exact mechanism of how immune adjuvants function still remains largely unknown, despite their long history of use. This work reports the properties of alum and the related compounds Al(OH)3 or Al2O3. Experiments were performed in rats to determine the relative adjuvancy of silica, talc, ground glass, Al2O3, SnO2, ZrO2, hematite and magnetite. Antibody response and cell-mediated immunity (CMI) to ovalbumin (OVA) were determined and were found to be significantly enhanced by silica and talc. Antibody response to OVA was moderately enhanced by Al2O3, hematite, and magnetite, while CMI to OVA was not affected, SnO2, ZrO2, and ground glass only gave a slight adjuvant effect. The magnitude of adjuvancy appeared to correlate with the magnitude of the inflammatory response produced by each metal oxide and also correlated with their surface area. No correlation could be drawn between the hydrophilicity or hydrophobicity of the metal oxides and the magnitude of their adjuvancy.

Adjuvants, Immunologic↗

PubMed1997

Psychological dysfunction in patients with reflex sympathetic dystrophy.

Patients with reflex sympathetic dystrophy (RSD) often present with pain and disability that cannot be explained on the basis of objective physical findings. This has led some to speculate that RSD may be caused or mediated by non-organic factors. Unfortunately, there have been few studies using standardized measures of mood and illness behavior that have compared patients with RSD to patients with other chronic pain disorders. The goal of the present study, therefore, was to compare the pattern of psychological dysfunction in patients with RSD to the pattern of dysfunction in patients with chronic back pain and local neuropathic pain. Patients with back pain resemble those with RSD in that both may report symptoms that cannot be reconciled with objective physical findings. Patients with local neuropathy, by contrast, report pain that is both circumscribed and consistent with a known organic cause. The records of 253 patients attending a tertiary pain service were retrospectively reviewed and three distinct (non-overlapping) diagnostic groups were formed: 25 were assigned to the RSD group; 44 to the back pain group; and 21 to the local neuropathy group. Using a set of stringent criteria to diagnose RSD and an analysis of covariance to control for differences in symptom duration and age, the present study found no evidence to suggest that patients with RSD were psychologically unique. Instead, RSD patients were remarkably similar to those with local neuropathy in terms of their symptom reporting, illness behavior, and psychological distress. The only exception was that RSD patients had more disability days during the preceding 6 months than those with local neuropathy (P < 0.05). The back pain group, on the other hand, presented with more diffuse pain complaints (P < 0.05) and had a greater number of non-specific medical symptoms (P < 0.05) compared to either the RSD or local neuropathy group. In contrast to previous research using less stringent diagnostic criteria, there was no evidence of higher pain scores or lower levels of psychological distress among patients with RSD. In addition, a validated survey of childhood trauma found that sexual abuse, physical abuse, emotional abuse, and cumulative trauma were evenly distributed among all three diagnostic groups. The burden of proof would appear to be upon those who advocate the non-organic hypothesis to provide credible evidence of psychological involvement in the etiology of RSD.

Adaptation, Psychological↗

PubMed1997

N-(5-substituted) thiophene-2-alkylsulfonamides as potent inhibitors of 5-lipoxygenase.

Compound 4k N-[5-(4-fluoro)phenoxythien-2-yl]methanesulfonamide is representative of a new class of potent inhibitors of 5-lipoxygenase (5-LO). These versatile compounds exhibit dose-dependent inhibition of 5-LO with IC50s ranging from 20-100 nM in the rat basophilic leukemia (RBL-1) cell homogenate assay and submicromolar IC50s in both the RBL-1 and human peripheral blood leukocyte (PBL) whole cell assays. Compound 4k also showed significant anti-inflammatory activity in the adjuvant arthritic rat at an oral dose of 3 mg/kg.

Administration, Oral↗

PubMed1997

Nitroarylhydroxymethylphosphonic acids as inhibitors of CD45.

A series of nitroarylhydroxymethylphosphonic acids was synthesized and evaluated as inhibitors of CD45. It was discovered that both the alpha hydroxy and nitro groups are essential for activity. Potency is enhanced by the addition of a large lipophilic group on the aryl ring adjacent to the phosphonic acid moiety. Kinetics studies have shown that these compounds are competitive inhibitors and thus bind at the active site of this enzyme.

Amino Acid Sequence↗

PubMed1997

A model of the structure of HOO-Co.bleomycin bound to d(CCAGTACTGG): recognition at the d(GpT) site and implications for double-stranded DNA cleavage.

BACKGROUND: The bleomycins (BLMs) are a family of natural products used clinically as antitumor agents. In the presence of their required cofactors, iron and oxygen, BLMs bind to and mediate single-stranded and double-stranded DNA cleavage. Recently, two dimensional nuclear magnetic resonance (2D NMR) spectroscopic studies and molecular modeling have provided a picture of how the hydroperoxide form of cobalt BLM A2 (HOO-CoBLM), an analog of 'activated' iron BLM (HOO-FeBLM), binds to a d(GpC) motif and of the basis for both sequence specificity and chemical specificity of DNA cleavage. RESULTS: The solution structure of HOO-CoBLM bound to d(CCAGTACTGG) containing a 'hot spot' for double-stranded DNA cleavage at T5 and T15 is reported using constraints from 2D NMR spectroscopy. The mode of binding and basis for sequence specificity and chemical specificity of cleavage is almost identical to that of a d(GpC) motif. This structure has allowed formulation of a structural model for how a single molecule of FeBLM can mediate a double-stranded DNA cleavage event without dissociation from the DNA. CONCLUSIONS: The structural similarity of HOO-CoBLM bound to d(GpT) in d(CCAGTACTGG) compared to a d(GpC) motif suggests a general paradigm for the binding of HOO-CoBLM to DNA and, by analogy, for the binding of the biological significant entity HOO-FeBLM.

Binding Sites↗

PubMed1997

Epstein-Barr virus BHRF1 prohibits the cells of nasopharyngeal carcinoma from apoptosis.

Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC). The BHRF1 EBV protein is expressed at high levels in productively infected cells and certain latently infected cells. In order to investigate the effect of expression of BHRF1 on the biological behaviour of NPC cells, we constructed the BHRF1 high expression vector and transfected it into the NPC cell line, CNE2. Then, the alteration of proliferation and apoptotic rates in the cells were tested before and after camptothecin treatment. After treatment by camptothecin, BHRF1-CNE2 cells could constantly and slowly proliferate and its apoptotic rate was less than in control groups, and the number of cells in the G phase decreased and in the S phase increased. So, it suggests that BHRF1 expression can enhance the resistibility of CNE2 cells to DNA-damaging agents that cause apoptosis.

Antineoplastic Agents, Phytogenic↗

PubMed1997

Spectrum of mutations in the RPGR gene that are identified in 20% of families with X-linked retinitis pigmentosa.

The RPGR (retinitis pigmentosa GTPase regulator) gene for RP3, the most frequent genetic subtype of X-linked retinitis pigmentosa (XLRP), has been shown to be mutated in 10%-15% of European XLRP patients. We have examined the RPGR gene for mutations in a cohort of 80 affected males from apparently unrelated XLRP families, by direct sequencing of the PCR-amplified products from the genomic DNA. Fifteen different putative disease-causing mutations were identified in 17 of the 80 families; these include four nonsense mutations, one missense mutation, six microdeletions, and four intronic-sequence substitutions resulting in splice defects. Most of the mutations were detected in the conserved N-terminal region of the RPGR protein, containing tandem repeats homologous to those present in the RCC-1 protein (a guanine nucleotide-exchange factor for Ran-GTPase). Our results indicate that mutations either in as yet uncharacterized sequences of the RPGR gene or in another gene located in its vicinity may be a more frequent cause of XLRP. The reported studies will be beneficial in establishing genotype-phenotype correlations and should lead to further investigations seeking to understand the mechanism of disease pathogenesis.

Carrier Proteins↗

PubMed1997

Analysis of the RPGR gene in 11 pedigrees with the retinitis pigmentosa type 3 genotype: paucity of mutations in the coding region but splice defects in two families.

X-linked retinitis pigmentosa (XLRP) is a severe form of inherited progressive retinal degeneration. The RP3 (retinitis pigmentosa type 3) locus at Xp21.1 is believed to account for the disease in the majority of XLRP families. Linkage analysis and identification of patients with chromosomal deletion have refined the location of the RP3 locus and recently have led to the cloning of the RPGR (retinitis pigmentosa GTPase regulator) gene, which has been shown to be mutated in 10%-15% of XLRP patients. In order to systematically characterize the RPGR mutations, we identified 11 retinitis pigmentosa type III (RP3) families by haplotype analysis. Sequence analysis of the PCR-amplified genomic DNA from patients representing these RP3 families did not reveal any causative mutation in RPGR exons 2-19, spanning >98% of the coding region. In patients from two families, we identified transition mutations in the intron region near splice sites (IVS10+3 and IVS13-8). RNA analysis showed that both splice-site mutations resulted in the generation of aberrant RPGR transcripts. Our results support the hypothesis that mutations in the reported RPGR gene are not a common defect in the RP3 subtype of XLRP and that a majority of causative mutations may reside either in as yet unidentified RPGR exons or in another nearby gene at Xp21.1.

Adult↗

PubMed1997

Developmentally regulated expression of peanut agglutinin (PNA)-specific glycans on murine thymocytes.

Intrathymic maturation of T lymphocytes is characterized by variable expression of O-linked Gal beta 1,3GalNAc glycans reactive with peanut agglutinin (PNA) lectin. Recent studies on human thymocytes show that conversion from PNA+ to PNA- phenotype is correlated with increased expression of alpha 2,3 O-linked sialyltransferase (ST), which sialylates Gal beta 1,3GalNAc glycans, masking their binding sites for PNA. Interestingly, alpha 2,3 O-linked ST expression is highest within the regions of the thymus containing the most immature and most mature thymocyte subsets, suggesting that PNA-specific glycans are intermittently masked by sialylation during thymic selection processes. Here, we studied expression of PNA receptors on developing thymocytes in the murine system using thymocytes from both normal mice and transgenic mice that are genetically arrested at the early phases of T cell development. Our results confirm and extend recent findings in the human system by showing that murine T cells sequentially progress from PNAlo-->PNAhi-->PNAlo stages during their differentiation within the thymus. In addition, our data demonstrate that a similar set of polypeptides is variably masked by sialylation throughout T cell development.

Animals↗

PubMed1997

Counteracting Fusarium proliferatum toxicity in broiler chicks by supplementing drinking water with Poultry Aid Plus.

To test whether Poultry Aid Plus (PAP, a commercial product for drinking water application) could reduce the stress on broiler chicks caused by Fusarium proliferatum contamination of feed, water (with or without PAP application, according to the manufacturer's instructions), and feed (experimentally infected with F. proliferatum fermented and dried corn culture material, CM) were provided to broiler chicks for 3 wk. Eight treatments consisting of a 2 (with or without PAP in water) x 4 (0, 1, 2, and 4% CM in feed) factorial design were tested in four replicate cages of six chicks each. The diet with 2% CM reduced weight gain by 23%; this reduction was preventable by PAP water application. The diet with 4% CM caused a cumulative mortality of 87.5%, which was reduced by PAP water application to 50%. The population half-life of the chicks on the diet with 4% CM was 6.5 d; this half-life was prolonged to at least 21 d by PAP water application. The PAP application also reduced the relative weight of the small intestine and promoted Lactobacillus colonization of the large intestine regardless of the level of CM in feed. Therefore, water application of PAP can be a prophylactic measure for F. proliferatum toxicity in poultry production.

Animals↗

PubMed1997

Tungstic acid reduction of cold-resistant stress-induced ulceration in rats.

Sprague-Dawley rats were restrained at 4 degrees C for 2 h (stress). Tungstic acid in a single dose of 0.01, 0.1, 1, 10, 100 or 300 mg/kg (dissolved in distilled water) was administered intragastrically to animals 30 min prior to stress. Stress induced significant gastric mucosal damage, whereas tungstic acid pretreatment dose-dependently reduced lesion formation. Doses of tungstic acid of 1 mg/kg and higher significantly (P < 0.05-0.001) decreased ulcers. The mucosal mast cell counts in rats pretreated with tungstic acid were significantly higher than those of control rats. In motility experiments using oral administration of amberlite pellets, pretreatment with tungstic acid dose-dependently reduced the gastric emptying rate during a 1 h period of stress. Gastric mucosal xanthine oxidase and superoxide dismutase (SOD) activities, after pretreatment with a single dose of tungstic acid, were not altered in stressed animals. It is suggested that tungstic acid effectively antagonizes stress-induced gastric ulcers, possibly by decreasing motility and mass cell degranulation. Xanthine oxidase and SOD activities and mucous content were not changed in the gastric mucosa by the present method of tungstic acid administration.

Animals↗

PubMed1997

Composition and role of extracellular polymers in methanogenic granules.

Methanobacterium formicicum and Methanosarcina mazeii are two prevalent species isolated from an anaerobic granular consortium grown on a fatty acid mixture. The extracellular polysaccharides (EPS) were extracted from Methanobacterium formicicum and Methanosarcina mazeii and from the methanogenic granules to examine their role in granular development. The EPS made up approximately 20 to 14% of the extracellular polymer extracted from the granules, Methanobacterium formicicum, and Methanosarcina mazeii. The EPS produced by Methanobacterium formicicum was composed mainly of rhamnose, mannose, galactose, glucose, and amino sugars, while that produced by Methanosarcina mazeii contained ribose, galactose, glucose, and glucosamine. The same sugars were also present in the EPS produced by the granules. These results indicate that the two methanogens, especially Methanobacterium formicicum, contributed significantly to the production of the extracellular polymer of the anaerobic granules. Growth temperature, substrates (formate and H(inf2)-CO(inf2)), and the key nutrients (nitrogen and phosphate concentrations) affected polymer production by Methanobacterium formicicum.

Journal Article↗

PubMed1997

The effects of remaining axons on motoneuron survival and NOS expression following axotomy in the adult rat.

it is well known that target removal or distal axotomy in adult animals results in no detectable loss of motoneurons in the spinal cord. By performing axotomy in the seventh cervical (C7) spinal nerve at different distances from the spinal cord (0, 2, 4, 8 mm respectively), this study examines the effects of the remaining axons on motoneuron survival as well as NOS expression. Results of the present study show that axotomy in adult peripheral nerve can induce significant spinal motoneuron death if axotomy is performed close enough to the spinal cord. The closer the axotomy to the spinal cord, the higher the rate of motoneuron loss was observed. The most significant motoneuron loss was found in animals with axotomy at 0 mm to the cord, which was coincident with the highest percent of NOS-positive motoneurons. The rate of survival of motoneurons increases and the percent of NOS-positive motoneurons decreases when the distance of the axotomy to the cord increases from 0 to 4 mm. No significant motoneuron loss nor NOS-positive motoneurons were observed when axotomy was performed at 4 mm and distally. These results indicate that the survival of spinal motoneurons in adult rat following axotomy is largely dependent on the length of the remaining axons. The longer the remaining axon, the better for motoneuron survival. The minimal length of axon for motoneuron survival in adult rat seems to be at least 4 mm.

Animals↗

PubMed1997

The relationship between surface free-energy and kinetics in the mineralization and demineralization of dental hard tissue.

The interfacial free-energy is an important factor in the regulation of mineralization and dissolution at the surfaces of dental hard tissues. However, few thermodynamic studies have been aimed at the elucidation of the interfacial terms. Contact angle measurements (sessile drop and thin layer wicking) and kinetic dissolution and growth techniques have been used to study the interfacial properties of root dentin (D), human enamel (E), and hydroxyapatite (HAP). The interfacial tensions between water (w) and each of these phases were calculated from contact angle data according to surface tension components theory. The values gamma wD = 4.5 x 10(-3) J m-2, gamma wE = 8.8 x 10(-3) J m-2, and gamma w,HAP = 10.4 x 10(-3) J m-2 were of the same order of magnitude as those obtained from dissolution kinetic data (pH = 4.5): gamma wD = 1.4 x 10(-3) J m-2, gamma wE = 3.2 x 10(-3) J m-2, and gamma wHAP = 9.3 x 10(-3) J m-2. Kinetics studies of the crystallization of HAP on HAP, dentin, and enamel yielded the interfacial free-energy values, gamma wHAP = 17.1 x 10(-3) J m-2, 17.7 x 10(-3) J m-2, and 9.4 x 10(-3) J m-2, respectively, probably reflecting the interfacial energies of the deposited phases rather than those of the dental hard-tissue substrata. The lower interfacial tension values are consistent with the higher solubilities of these solid phases: logKSO = -52.0, -55 approximately 57, and -58 approximately 59, for root dentin, enamel, and HAP, respectively, expressed as an equivalent HAP ionic product. The higher interfacial free-energy is also consistent with the slower mineralization of HAP on dentin and enamel surfaces.

Crystallization↗

PubMed1997

Enhanced cytotoxicity of alkyl viologens and N,N'-diamino analogs toward cultured murine leukemia L1210 cells under vortex-stirring with a high molecular weight polyacrylic acid.

Alkyl viologens showed cytotoxicity when incubated with cultured murine leukemia L1210 cells for 48 h, whereas they were not cytotoxic when briefly incubated for 10 min. Under the permeabilizing conditions achieved by vortex-stirring with a high molecular weight polyacrylic acid (A-119), appreciable cytotoxicity was shown even after a 10-min exposure to any of the alkyl and amino viologens examined. Acetylamino viologen showed no cytotoxicity regardless of the presence or absence of A-119. This permeabilizing procedure was demonstrated to be applicable to internalize water-soluble positively charged viologen molecules into the cell.

Acrylic Resins↗