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Biomedical subjects

A Binder

Publications and source records attributed to A Binder.

At least 37 records · Page 2Linked to original sources

Determination of the initial DNA damage and residual DNA damage remaining after 12 hours of repair in eleven cell lines at low doses of irradiation.

PURPOSE: To determine the relationship between DNA damage and radiosensitivity at low doses (1-10 Gy) for the initial DNA damage and residual DNA damage remaining after 12-h repair. MATERIALS AND METHODS: Eleven cell lines, normal human lung epithelial L132, HT29 human colon carcinoma, ATs4 human ataxia telangiectasia, normal CHO-K1 hamster, repair-deficient xrs1 and xrs5 mutants, repair-deficient SCID rodent cell line, the human normal fibroblast 1BR.3, human ataxia telangiectasia fibroblast AT1BR and the repair-deficient fibroblasts 180BR.B and 46BR.1 were irradiated with 60Co gamma-rays. Radiosensitivity was measured by clonogenic survival assay. DNA damage was measured by fluorometric analysis of DNA unwinding (FADU). RESULTS: The radiosensitivity in the 11 cell lines ranged from SF2 of 0.02-0.61. By FADU assay, the undamaged DNA at 5-Gy ranged from 56 to 93%. The initial DNA damage and radiosensitivity were highly correlated (r2 = 0.81). After 5-Gy irradiation and 12-h repair, two groups of cell lines emerged. Group 1 restored undamaged DNA to a level ranging from 94 to 98%. Group 2 restored the undamaged DNA to a level ranging from 77 to 82%. No correlation was seen between residual DNA damage remaining after 12-h repair and radiosensitivity. CONCLUSION: It is shown that the initial DNA damage correlates with radiosensitivity at low doses of irradiation. This suggests that the initial DNA damage must be considered as a determinant for radiosensitivity.

Animals↗

Effect of sympathetic activity on capsaicin-evoked pain, hyperalgesia, and vasodilatation.

BACKGROUND: Painful nerve and tissue injuries can be exacerbated by activity in sympathetic neurons. The mechanisms of sympathetically maintained pain (SMP) are unclear. OBJECTIVE: To determine the effect of cutaneous sympathetic activity on pain induced by primary afferent C-nociceptor sensitization with capsaicin in humans. METHODS: In healthy volunteers capsaicin was applied topically (n = 12) or injected into the forearm skin (n = 10) to induce spontaneous pain, dynamic and punctate mechanical hyperalgesia, and antidromic (axon reflex) vasodilatation (flare). Intensity of pain and hyperalgesia, axon reflex vasodilatation (laser Doppler), and flare size and area of hyperalgesia (planimetry) were assessed. The local skin temperature at the application and measurement sites was kept constant at 35 degrees C. In each individual the analyses were performed during the presence of high and low sympathetic skin activity induced by whole-body cooling and warming with a thermal suit. By this method sympathetic vasoconstrictor activity is modulated in the widest range that can be achieved physiologically. The degree of vasoconstrictor discharge was monitored by measuring skin blood flow (laser Doppler) and temperature (infrared thermometry) at the index finger. RESULTS: The intensity and spatial distribution of capsaicin-evoked spontaneous pain and dynamic and punctate mechanical hyperalgesia were identical during the presence of high and low sympathetic discharge. Antidromic vasodilatation and flare size were significantly diminished when sympathetic vasoconstrictor neurons were excited. CONCLUSIONS: Cutaneous sympathetic vasoconstrictor activity does not influence spontaneous pain and mechanical hyperalgesia after capsaicin-induced C-nociceptor sensitization. When using physiologic stimulation of sympathetic activity, the capsaicin model is not useful for elucidating mechanisms of SMP. In neuropathic pain states with SMP, different mechanisms may be present.

Adult↗

beta-2 Adrenergic receptor variants affect resting blood pressure and agonist-induced vasodilation in young adult Caucasians.

Recent evidence suggests that the prodownregulatory Gly16 allele of the beta-2 adrenergic receptor (beta-2 AR) is associated with essential hypertension in African Caribbeans. To further investigate the effect of the glycine (Gly)16 and arginine (Arg)16 beta-2 AR variants on hemodynamics, we investigated the agonist-mediated in vivo vasodilation in normotensive Austrian Caucasians and analyzed the results with respect to the Gly16/Arg16 polymorphism. Fifty-seven normotensive men, 20 to 32 years of age with body mass index of 18.7 to 29.9 kg/m2, were genotyped for the Arg16/Gly16 beta-2 AR alleles. All 15 Gly16/Gly16 subjects, all 12 Arg16/Arg/16 subjects, and 27 of 30 heterozygous subjects underwent hemodynamic measurements while supine after an overnight fast. The observers were unaware of the subjects' genotypes. The subjects received a graded infusion of the selective beta-2 AR agonist salbutamol (0.07, 0.14, and 0.21 microgram/kg per minute, respectively), each dose over 8 minutes. Stroke volume and blood pressure were determined continuously by means of impedance cardiography and oscillometry, respectively. The last 4 minutes of each infusion were evaluated statistically. Basal mean blood pressure was higher in the Gly16/Gly16 subjects compared with Arg16/Arg16 subjects (mean+/-SD: 81.6+/-6.14 versus 75.2+/-4.93 mm Hg, P<0.01). Homozygous Gly16 subjects showed a significantly decreased vasodilation during the first dose of salbutamol infusion compared with Arg16/Arg16 subjects (Deltatotal peripheral resistance index -17.9+/-14.4 versus -30. 6+/-8.3%, P<0.01) despite increased sympathetic counterregulation in the Arg16/Arg16 group (Deltaheart rate +16.9+/-7.0% versus +8.6+/-7. 0%, P<0.01; Deltacardiac index +39.5+/-18.5% versus 21.4+/-18.8%, P<0.05). Our results provide additional evidence that the Gly16/Arg16 alleles of the beta-2 AR are intimately related to blood pressure regulation and deserve further studies in the pathogenesis of essential hypertension.

Adrenergic beta-Agonists↗

Lunar surface magnetic fields and their interaction with the solar wind: results from lunar prospector

The magnetometer and electron reflectometer experiment on the Lunar Prospector spacecraft has obtained maps of lunar crustal magnetic fields and observed the interaction between the solar wind and regions of strong crustal magnetic fields at high selenographic latitude (30 degreesS to 80 degreesS) and low ( approximately 100 kilometers) altitude. Electron reflection maps of the regions antipodal to the Imbrium and Serenitatis impact basins, extending to 80 degreesS latitude, show that crustal magnetic fields fill most of the antipodal zones of those basins. This finding provides further evidence for the hypothesis that basin-forming impacts result in magnetization of the lunar crust at their antipodes. The crustal magnetic fields of the Imbrium antipode region are strong enough to deflect the solar wind and form a miniature (100 to several hundred kilometers across) magnetosphere, magnetosheath, and bow shock system.

Journal Article↗

Antibodies to Klebsiella pneumoniae lipopolysaccharide in patients with ankylosing spondylitis.

The role of microbial lipopolysaccharides (LPS) in the aetiopathogenesis of ankylosing spondylitis (AS) is a matter of continuing debate. In this study, class-specific IgG, IgA and IgM antibodies against Klebsiella pneumoniae, Escherichia coli, Salmonella typhimurium and Salmonella enteritidis LPS were measured by enzyme-linked immunosorbent assay (ELISA) in 100 AS patients, 50 rheumatoid arthritis (RA) patients and 50 healthy control subjects. The AS patients had significantly elevated levels of IgG and IgA antibodies against K. pneumoniae LPS (P < 0.001) and IgA antibodies against E. coli LPS (P < 0.05) compared to healthy controls. There were no significant elevations of antibody levels against S. typhimurium and S. enteritidis in the three study groups. In addition, there was a correlation between IgG and IgA anti-K. pneumoniae LPS antibody levels and the acute-phase reactant C-reactive protein (P < 0.001).

Adult↗

Essential hypertension in African Caribbeans associates with a variant of the beta2-adrenoceptor.

Populations of West African ancestry dwelling in Western communities exhibit greater prevalence of human essential hypertension and higher rates of end-organ damage. The sympathetic nervous system influences cardiac output, vascular tone, renal sodium reabsorption, and renin release and could be implicated in enhanced vascular responsiveness observed in African hypertensives. Such an effect could arise from genetic variants that alter agonist response of alpha-adrenoceptors, leading to enhanced vasoconstriction, or attenuate beta2-adrenoceptor-mediated vasodilatation. Indeed, there is evidence of a blunted vasodilator response to the beta-agonist isoprenaline in African Americans. A variant of the beta2-adrenoceptor gene that encodes glycine rather than arginine at position 16 (Arg16-->Gly) has been shown to confer exaggerated agonist-mediated receptor downregulation, which might attenuate vasodilator response. One hundred thirty-six unrelated hypertensives and 81 unrelated normotensives of African Caribbean origin were identified from primary care on the island of St Vincent. Genomic DNA from these subjects was analyzed for the presence of the Gly16 and Arg16 alleles by using an allele-specific polymerase chain reaction method. We report strong support for association of the prodownregulatory glycine 16 variant of the beta2-adrenoceptor gene with hypertension in African Caribbeans from St Vincent and the Grenadines (chi2=18.9, P=.000014, 1 df). This observation, coupled with reports of attenuated vasodilator responses to beta-agonists among people of West African ancestry, may provide a mechanism for enhanced vascular reactivity and identify a candidate gene for hypertension in this ethnic group.

Adult↗

The underlying cellular mechanism of fibrosis.

Fibrosis is a common sequela of various exogenous insults to a variety of parenchymal tissues. The underlying mechanisms of the induction and progression of fibrosis both at the molecular and cellular level have not been clarified so far. In the present study the cellular processes that ultimately may lead to interstitial fibrosis are described using the model of radiation-induced terminal differentiation in the fibroblast/fibrocyte cell system. The data reported herein will provide evidence that exogenously induced changes in the proliferation and differentiation pattern of the fibroblast/fibrocyte cell system based on either autocrine and/or paracrine mediators represent the underlying cellular mechanism of fibrosis. Using co-culture systems of parenchymal cells (fibroblasts and type II pneumocytes), the intercellular communication via cytokines, which may lead to fibrosis have been studied. TGF beta 1 could be described as one key modulator of these cellular processes.

Animals↗

Molecular mimicry and ankylosing spondylitis: possible role of a novel sequence in pullulanase of Klebsiella pneumoniae.

Molecular mimicry has been shown between two sequences of Klebsiella pneumoniae pulD secretion protein (DRDE) with HLA-B27 (DRED) and pulA (pullulanase) enzyme (Gly-X-Pro) with types I, III and IV collagen respectively. IgG antibody levels in AS patients were elevated against 16mer synthetic peptides of HLA-B27 and pulD by enzyme immunosorbent assay (ELISA) compared to controls (P < 0.001). ELISA assays against K. pneumoniae grown in the absence and presence of pullulan demonstrated significant levels of IgA antibody in AS patients compared to controls (P < 0.001). Increased IgA and IgG antibody levels to pulA and types I and IV collagen were observed in AS patients compared to controls (P < 0.001). These observations could be relevant in the sequence of molecular events in AS.

Amino Acid Sequence↗

[Effect of ethoxyquin on the utilization of selenium in growing pigs].

In a 2 x 3 factorial arrangement with 30 male castrates (German Landrace; 13.7 +/- 1.7 kg b.w.), after a 2 week feeding period with a maize/torula yeast basal diet poor in selenium and without vitamin E supplementation, the effect of two ethoxiquin concentrations (0 and 150 mg/kg) und 3 selenium concentrations (0.075, 0.10 and 0.125 mg/kg) on growth, the activity of the Se dependent GSH-Px in the erythrocytes and the Se concentrations in liver, kidney, heart and diaphragm was measured after 4 weeks on the experimental diets. Under the experimental conditions chosen ethoxiquin had no effect of any of the parameters studied. Selenium supplementation significantly increased the enzyme activity and the Se concentrations in the organs and tissues analyzed.

Aging↗

Shared amino acid sequences between major histocompatibility complex class II glycoproteins, type XI collagen and Proteus mirabilis in rheumatoid arthritis.

OBJECTIVES: To show molecular similarity between two sequences of Proteus mirabilis (haemolysin--ESRRAL; urease--IRRET) with HLA-DR antigens (EQRRAA) which are associated with rheumatoid arthritis (RA) and type XI collagen (LRREI), respectively; and, in patients with RA, to measure levels of antibody against a 16-mer synthetic peptide containing the ESRRAL sequence, and the haemolysin and urease proteins of Proteus mirabilis. METHODS: The homologous sequences EQRRAA and ESRRAL were modelled with Alchemy III, using the crystalline structure of DRB1*0101 (HLA-DR1). Sera from 40 patients with RA, 30 with ankylosing spondylitis (AS), and 30 controls were tested against synthetic ESRRAL peptide and the haemolysin of Proteus mirabilis by enzyme linked immunosorbent assay. Similar tests were also carried out on sera from 20 patients with RA, 40 with AS, and 15 controls, against Proteus mirabilis urease. RESULTS: Molecular modelling of the homologous sequences ESRRAL/EQRRAA and IRRET/LRREI showed stereochemical similarities. Antibodies to the 16-mer synthetic peptide containing the ESRRAL sequence, the haemolysin, and urease proteins were significantly increased in RA patients compared with AS patients (p < 0.001) and healthy controls (p < 0.001). No such increases were observed with three control peptides including the EDERAA sequence of DRB1*0402 (HLA-DR4/Dw10), the haemolysin proteins of Streptococcus pyogenes and Vibrio parahaemolyticus, and the urease of Bacillus pasteurii. CONCLUSION: The additive effect of the immune responses to the two Proteus mirabilis antigens, haemolysin (ESRRAL) and urease (IRRET), could be relevant in the aetiopathogenesis of RA.

Adult↗

Elevation in anti-Proteus antibodies in patients with rheumatoid arthritis from Bermuda and England.

OBJECTIVE: To determine whether patients with rheumatoid arthritis (RA) from Bermuda and England have an increased anti-Proteus antibody titer when compared to healthy Bermudian and English controls, and to ascertain whether any increase in antibody titer is specific by testing 4 other microbes, Escherichia coli and 3 normal anaerobic bowel bacteria. METHODS: Antibody titers were measured by ELISA and indirect immunofluorescence (IIFA) under coded conditions. RESULTS: Elevated titers of anti-Proteus antibodies were demonstrated in 34 patients with active RA from Bermuda when compared to 33 healthy Bermudian controls by ELISA (p < 0.001) and IIFA (p < 0.001). An elevation of anti-Proteus antibodies was also observed in 34 patients with RA from England when compared to 30 healthy English controls again by ELISA (p < 0.001). A similar antibody elevation in 31 patients with RA from England was observed when compared to 30 healthy controls when measured by IIFA (p < 0.001). However, there was no significant elevation in antibody titers against E. coli or the 3 normal bowel flora isolates in the patients with RA from both countries compared to their respective controls, when measured by ELISA. CONCLUSION: A specific elevation in the immune response to Proteus mirabilis has been demonstrated in patients with RA from both Bermuda and England. However, this study cannot distinguish between antibody association with disease per se and association with disease activity. The role of Proteus in RA and the effect of anti-Proteus therapy in patients with RA merits further study.

Adult↗

[Sonographic diagnosis of secondary blastomas of the thyroid gland].

The value of sonography for examining the thyroid has long been recognised. Secondary tumours are rarely demonstrated surgically. We examined retrospectively 14 patients with histologically proven secondary tumours which had been investigated by us tumours which had been investigated by us preoperatively. We were unable to determine any differential features between primary and secondary thyroid tumours. One can point out only that the development of thyroid tumours in the presence of a known primary may be due to metastases.

Adult↗

[Native radiologic staging of osteoporosis--CT densitometry of lumbar vertebral spongiosa. A correlation study].

Lumbar spine radiographs in 47 patients with manifest or clinically suspected osteoporosis were evaluated, using a staging system, and correlated to quantitative computed tomography (QCT) of lumbar vertebrae. The accuracy of osteoporosis assessment, obtained with plain film analysis, was 60%, the sensitivity 67%, the specificity 56%. Statistical correlation showed high standard deviation of each of the QCT-mean values according to the respective stage groups, and altogether poor linear correlation between increasing morphological stages of osteoporosis and decreasing QCT-values. As our results show plain film differentiation of normal from reduced trabecular bone mineral content is unreliable, even by use of a staging system. The diagnostic value of spine radiographs therefore remains limited to demonstration of advanced osteoporotic changes.

Absorptiometry, Photon↗

Interstitial MR lymphography with iron oxide particles: results in tumor-free and VX2 tumor-bearing rabbits.

OBJECTIVE: MR lymphography with interstitial injection of superparamagnetic iron oxide particles was optimized in normal rabbits by investigating the pattern of signal reduction in lymph nodes as a function of dose and time after administration. The optimized examination procedure was then used in a rabbit tumor model to study the potential of superparamagnetic iron oxide--enhanced MR lymphography in the detection of metastatic lymph node involvement. MATERIALS AND METHODS: The popliteal and iliac lymph nodes of 18 normal rabbits were imaged to study the dose response and time course of the effect of the contrast agent. For the dose response study, six doses of 2-50 mumol of iron per extremity were administered to three animals per dose, and MR images were obtained before and 12 hr after administration. For the time course study, 20 mumol of iron per extremity was administered to four animals, and images were obtained before and 6 hr to 42 days after administration. VX2 tumor-bearing rabbits were examined 12 hr after administration of 20 mumol (10 animals) and 50 mumol (three animals) of iron per extremity. Superparamagnetic iron oxide was injected into the foot pad of the hind limb. T1-, T2-, and proton density-weighted MR images were obtained with a 1.5-T unit. RESULTS: In normal rabbits, a profound and homogeneous loss of signal intensity was found with doses of 2-5 mumol of iron per extremity in popliteal lymph nodes and with doses of 20-30 mumol in the iliac lymph nodes. Superparamagnetic iron oxide caused maximal loss of signal intensity in both popliteal and iliac lymph nodes 12 hr after administration. In tumor-bearing rabbits, different degrees of metastatic displacement of lymph nodes were discernible, and even small metastases (3 mm in diameter) could be visualized when using the optimized examination protocol and the proton density-weighted spin-echo sequence. CONCLUSION: We conclude that interstitial MR lymphography with superparamagnetic iron oxide enables the detection of lymph node metastases and therefore is a promising technique for improved diagnostic imaging of lymph nodes in the staging of tumors.

Animals↗