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M Wahl

Publications and source records attributed to M Wahl.

At least 19 recordsLinked to original sources
PubMed2001

Involvement of prostanoid release in the mediation of UTP-induced cerebrovascular contraction in the rat.

The interaction between uridine-5'-triphosphate (UTP) and prostanoids was studied in isolated rat middle cerebral arteries (MCAs). The strong contractions in MCA segments induced by UTP were weakened significantly by indomethacin and more markedly by the thromboxane receptor antagonist ICI 192605. Thromboxane A(2) (TXA(2)) release by MCAs was below the detection limit of the chemiluminescence enzyme immunoassay, but increased TXA(2) formation was detected in basilar arteries in the presence of UTP. Prostacyclin (PGI(2)) formation by MCAs also increased in the presence of UTP. These results suggest that UTP stimulates the release of both TXA(2) and PGI(2) from the rat MCA but the vascular effect of TXA(2) is dominant.

Animals↗
PubMed2001

Small scale variability of benthic assemblages: biogenic neighborhood effects.

In this study, patterns of community development were investigated within vs. outside 'habitats'. These habitats represented five different monospecific assemblages of one of the following species: the brown alga Fucus serratus, the red alga Delesseria sanguinea, the green alga Enteromorpha intestinalis, the seagrass Zostera marina and the blue mussel Mytilus edulis. Natural assemblages were allowed to develop on paired artificial substrata-separated by ca. 1 m-within (treatment) vs. outside (control) of habitats. The same colonizer species settled on treatment and control substrata for given habitats. However, after 5 months of settlement and post-settlement dynamics, their proportional abundance and the structure of treatment and control assemblages differed in many instances. Variability among replicates of a given treatment, seperated by up to 50 m, was large, indicating a patchy spatial distribution of organisms. Despite this spatial heterogeneity among within-treatment replicates, analysis of similarity revealed that in most instances significantly different assemblages developed between treatments on a small spatial scale depending on whether substrata were positioned within as compared to outside a given habitat.Consequently, the algae, seagrass or mussels constituting a habitat seem to control the structure of the benthic assemblage developing in their vicinity by one or more possible mechanisms: reduction of larval advection, exudation of metabolites that influence settlement and/or post-settlement survival, and/or-in the case of mussel assemblages-predation on larvae.In addition to spatial variability in larval supply, stochasticity in succession, substratum heterogeneity, competition and predation effects, this investigation reveals the potential of a further assemblage structuring factor: the impact of neighboring organisms.

Journal Article↗
PubMed2001

Inhibition of endothelin-1 by the competitive ET(A) receptor antagonist Ro 61-1790 reduces lesion volume after cold injury in the rat.

The aim of the present study was to investigate whether endothelin-1 (ET-1) in cerebral arteries is inhibited by the new, non-peptidergic ET(A) receptor antagonist Ro 61-1790 and, if it is, whether that inhibition reduces the lesion volume induced by cold injury in the parietal cortex. In vitro experiments were performed by measuring the isometric contractions of the rat middle cerebral and basilar arteries. A cold lesion was induced in vivo by the application of a pre-cooled (-78 degrees C) copper cylinder (diameter 3 mm) to the intact dura of rats for 6 s. After 24 h, lesion volume was determined by the triphenyltetrazolium method. In vitro, ET-1 (10(-12) - 3x10(-7) M) caused a dose-dependent contraction under resting conditions in the middle cerebral and basilar arteries of control rats. Ro 61-1790 (3x10(-9) M, 10(-7) M) shifted the concentration-effect curves for ET-1 in a parallel fashion (Emax unaltered). Post-treatment with Ro 61-1790 (10(-7)-10(-5) M) also inhibited the prior contraction elicited by ET-1 (3x10(-9) M) significantly. In vitro ET-1 application 3 h after the intracerebroventricular in vivo administration of Ro 61-1790 showed that the antagonist had reached the arteries and was bound to their ET(A) receptors. Intracerebroventricular pre-treatment of Ro 61-1790 reduced significantly the lesion volume by 23% after the injury. We conclude that ET-1 is involved in the development of secondary brain damage and that intracerebroventricular treatment with Ro 61-1790 reduces the size of the brain lesion caused by cold injury.

Animals↗
PubMed2000

Time-resolved fluorescence imaging of slab gels for lifetime base-calling in DNA sequencing applications.

A compact time-resolved near-IR fluorescence imager was constructed to obtain lifetime and intensity images of DNA sequencing slab gels. The scanner consisted of a microscope body with f/1.2 relay optics onto which was mounted a pulsed diode laser (repetition rate 80 MHz, lasing wavelength 680 nm, average power 5 mW), filtering optics, and a large photoactive area (diameter 500 microns) single-photon avalanche diode that was actively quenched to provide a large dynamic operating range. The time-resolved data were processed using electronics configured in a conventional time-correlated single-photon-counting format with all of the counting hardware situated on a PC card resident on the computer bus. The microscope head produced a timing response of 450 ps (fwhm) in a scanning mode, allowing the measurement of subnano-second lifetimes. The time-resolved microscope head was placed in an automated DNA sequencer and translated across a 21-cm-wide gel plate in approximately 6 s (scan rate 3.5 cm/s) with an accumulation time per pixel of 10 ms. The sampling frequency was 0.17 Hz (duty cycle 0.0017), sufficient to prevent signal aliasing during the electrophoresis separation. Software (written in Visual Basic) allowed acquisition of both the intensity image and lifetime analysis of DNA bands migrating through the gel in real time. Using a dual-labeling (IRD700 and Cy5.5 labeling dyes)/two-lane sequencing strategy, we successfully read 670 bases of a control M13mp18 ssDNA template using lifetime identification. Comparison of the reconstructed sequence with the known sequence of the phage indicated the number of miscalls was only 2, producing an error rate of approximately 0.3% (identification accuracy 99.7%). The lifetimes were calculated using maximum likelihood estimators and allowed on-line determinations with high precision, even when short integration times were used to construct the decay profiles. Comparison of the lifetime base calling to a single-dye/four-lane sequencing strategy indicated similar results in terms of miscalls, but reduced insertion and deletion errors using lifetime identification methods, improving the overall read accuracy.

DNA↗
PubMed2000

Functional importance of neuronal nitric oxide synthase in the endothelium of rat basilar arteries.

The function of the neuronal isoform of nitric oxide synthase (nNOS) was studied by comparing the effects of the specific nNOS blocker 7-nitro indazole monosodium salt (7-NINA) with that of the general NOS inhibitor N(G)-nitro-L-arginine (L-NA) in isolated rat basilar arteries (BAs). 7-NINA had no significant effect on the resting tone of the vessels, while both L-NA and 1H-[1,2,4]oxadiazolo[4, 3-a]quinoxalin-1-one (ODQ), a selective inhibitor of the soluble guanylyl cyclase, induced contraction. The relaxant effect of bradykinin was attenuated in the presence of L-NA but was not changed by 7-NINA. In contrast, 7-NINA markedly reduced the acetylcholine-induced, endothelium-dependent relaxation. These results demonstrate that nNOS contributes significantly to the relaxant effect of acetylcholine, indicating the functional importance of this isoenzyme in the cerebrovascular endothelium.

Acetylcholine↗
PubMed2000

The cerebrocortical microcirculatory effect of nitric oxide synthase blockade is dependent upon baseline red blood cell flow in the rat.

The effects of nitric oxide synthase (NOS) blockade on the cerebrocortical microcirculation were investigated under physiological conditions in anesthetized ventilated rats using laser-Doppler (LD) flowmetry. LD flow values of the parietal cortex were determined before and after systemic administration of the NOS inhibitor N(G)-nitro-L-arginine-methyl-esther. NOS blockade reduced the LD flow significantly and the magnitude of the reduction was in close correlation with the baseline value. Synchronized sinus-wave-like LD flow oscillations were observed frequently after NOS inhibition and their appearance was also dependent on the high baseline flow values. These results indicate marked, baseline-dependent differences in the cerebrocortical blood flow response to the inhibition of the nitric oxide pathway, and may suggest that areas with high resting red blood cell flow express high NOS activity.

Animals↗
PubMed2000

Dual epitope recognition by the VASP EVH1 domain modulates polyproline ligand specificity and binding affinity.

The Ena-VASP family of proteins act as molecular adaptors linking the cytoskeletal system to signal transduction pathways. Their N-terminal EVH1 domains use groups of exposed aromatic residues to specifically recognize 'FPPPP' motifs found in the mammalian zyxin and vinculin proteins, and ActA protein of the intracellular bacterium Listeria monocytogenes. Here, evidence is provided that the affinities of these EVH1-peptide interactions are strongly dependent on the recognition of residues flanking the core FPPPP motifs. Determination of the VASP EVH1 domain solution structure, together with peptide library screening, measurement of individual K(d)s by fluorescence titration, and NMR chemical shift mapping, revealed a second affinity-determining epitope present in all four ActA EVH1-binding motifs. The epitope was shown to interact with a complementary hydrophobic site on the EVH1 surface and to increase strongly the affinity of ActA for EVH1 domains. We propose that this epitope, which is absent in the sequences of the native EVH1-interaction partners zyxin and vinculin, may provide the pathogen with an advantage when competing for the recruitment of the host VASP and Mena proteins in the infected cell.

Amino Acid Motifs↗
PubMed2000

Transduction of dendritic cells with Bcl-xL increases their resistance to prostate cancer-induced apoptosis and antitumor effect in mice.

We have shown that prostate cancer (PCa) causes apoptosis of dendritic cells (DC), which might block the development of specific antitumor immune responses. Analysis of murine prostatic carcinoma tissues revealed the significant decrease in intratumoral DC number during tumor progression. We demonstrated that the cytokine-mediated increase in DC survival was accompanied by an elevated expression of the anti-apoptotic protein Bcl-xL. Next, we evaluated the resistance to tumor-induced apoptosis and the antitumor efficiency of genetically engineered DC overexpressing Bcl-xL. DC were transduced with an adenoviral vector encoding the murine Bcl-xL gene and injected intratumorally. Data analysis revealed that treatment of PCa-bearing mice with Bcl-xL-transduced DC resulted in significant inhibition of tumor growth compared with the administration of nontransduced DC. Thus, our data suggest that the protection of DC from PCa-induced apoptosis might significantly increase the efficacy of DC-based therapies in cancer even in the absence of available tumor-specific Ags.

Animals↗
PubMed2000

Aminoguanidine reduces brain lesion volume after cold injury in the rat.

The aim of this study was to examine the effect of aminoguanidine (AG), which is thought to be an inducible nitric oxide synthase (iNOS) inhibitor, on lesion volume induced by cold injury in the parietal cortex of the rat. Cold lesion was induced by applying a precooled (-78 degrees C) copper cylinder (diameter: 3 mm) for 6 s to the intact dura. Lesion volume was determined using the triphenyltetrazolium-chloride method after 24 h. Pretreatment (1 h) and posttreatment (7.5 h) with AG [10 or 100 mg/kg body mass (BM)] reduced the lesion volume by 15 and 27%, respectively. However, posttreatment alone with AG (10 and 100 mg/kg BM) caused less of a reduction in lesion volume, by 8 and 20%, respectively. Pre- and posttreatment with AG also reduced the plasma nitrate/nitrite concentration compared with lesioned, saline-treated rats. Only a double therapy with AG (100 mg/kg BM) resulted in a significant reduction (48%) compared to saline alone, which was even larger (55%) compared to the sham group. The tissue nitrate/ nitrite concentration was significantly attenuated by pre- and posttreatment with AG (100 mg/kg BM) not only in the ipsilateral but also in the contralateral hemisphere. There was no difference regarding the parameter between shams and lesioned, saline-treated rats. Since combined pre- and posttreatment with AG reduced the lesion volume more than posttreatment alone and the plasma and tissue nitrate/nitrite concentrations were diminished during AG therapy compared to shams, we hypothesize that AG inhibits not only iNOS but also other enzymes, such as nNOS, diamine oxidase, and advanced glycation endproducts synthase.

Animals↗
PubMed2000

A novel brain trauma model in the mouse: effects of dexamethasone treatment.

We describe a novel methodological approach for inducing cold lesion in the mouse as a model of human cortical contusion trauma. To validate its reproducibility and reliability, dexamethasone (Dxm) was repeatedly applied to demonstrate possible antioedematous drug effects. Following the induction of anaesthesia with halothane, the dura was exposed via trephination. Using a micromanipulator a pre-cooled (-78 degrees C) copper cylinder, 3 mm in diameter, was pressed down to a depth of 1 mm onto the dura for 30 s under microscopic control. The body temperature was held constant at 37 degrees C throughout the procedure. Blood pressure (BP), measured by a modified photosensor-monitored tail-cuff method, and acid-base status were not significantly different when analysed before and after cold lesion and prior to sacrifice. However, there was a marginal mixed respiratory and metabolic acidosis. The antioedematous action of Dxm was studied in four standard pre-and post-treatment paradigms: 2x0.5 mg/kg (II), 2x12.5 mg/kg (III) and 4x6.25 mg/kg (IV: 3x pre-, 1x post-treatment: V: 1x pre-, 3x post-treatment). Physiological saline injections served as controls. High doses of Dxm (III-V) significantly attenuated the cold-lesion-induced loss of body mass. Dxm treatment also resulted in a reduction of brain water content (III; P<0.05), and brain swelling (IV; P<0.05) in the lesioned hemisphere, relative to controls. In conclusion, we have characterized a novel cold lesion model in the mouse to mimic traumatic brain injury and the beneficial effect of Dxm treatment on the extent of brain oedema.

Acid-Base Equilibrium↗
PubMed2000

Medical outcome of cocaine bodystuffers.

To describe the clinical course of cocaine "bodystuffers" presenting to regional emergency departments, a descriptive retrospective analysis was performed on all cases of cocaine bodystuffers received by a metropolitan poison control center and associated toxicology service from January 1993 to May 1994. We identified 46 cases of patients classified as bodystuffers. Of these, 34 patients (74%) remained asymptomatic. Eight patients (18%) had mild symptoms including hypertension and tachycardia that resolved with no treatment beyond decontamination or benzodiazepines (one patient). Two patients (4%) had moderate symptoms including agitation and fever that resolved with no treatment beyond decontamination or benzodiazepines (one patient). Two patients (4%) had severe symptoms including seizure and cardiac dysrhythmia. Both died. Radiographs of the abdomen were negative for foreign body in all 23 examinations performed. Mild cocaine intoxication is common in cocaine bodystuffers. Severe intoxication can occur, resulting in death. Abdominal radiographs are not of value for stuffers ingesting cellophane-wrapped packets. More experience is needed to determine the length of intensive care monitoring that these patients require.

Antidotes↗
PubMed2000

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Journal Article↗
PubMed2000

Effect of estradiol on insulin secreting INS-1 cells overexpressing estrogen receptors.

BACKGROUND: Estrogen has been shown to have profound effects on insulin and glucose metabolism in vivo. Indeed, estrogens were recently shown to modulate ion channel and secretory activities in endocrine cells. DESIGN AND METHODS: To investigate whether estrogenic influences are caused by direct effects on pancreatic beta-cells, we equipped INS-1 insulinoma cells with estrogen receptors and monitored insulin content and Ca(2+) fluxes as well as basal and stimulated insulin secretion upon different stimuli including glucose, the Ca(2+) ionophore ionomycin, the Ca(2+) channel agonist BayK8644, the protein kinase C activator TPA, and the adenylate cyclase activator forskolin. RESULTS AND CONCLUSION: Our data reveal that estradiol has no significant direct effect on proliferation rate, insulin content, basal and stimulated insulin output as well as Ca(2+) fluxes of insulin secreting cells in vitro, indicating that in vivo responses to estrogen on insulin and glucose metabolism result from indirect betacytotropic effects.

Calcium↗
PubMed1999

Crystal structure of an RNA duplex r(G GCGC CC)2 with non-adjacent G*U base pairs.

The crystal structure of a self-complementary RNA duplex r(GGGCGCUCC)2with non-adjacent G*U and U*G wobble pairs separated by four Watson-Crick base pairs has been determined to 2.5 A resolution. Crystals belong to the space group R3; a = 33.09 A,alpha = 87.30 degrees with a pseudodyad related duplex in the asymmetric unit. The structure was refined to a final Rworkof 17.5% and Rfreeof 24.0%. The duplexes stack head-to-tail forming infinite columns with virtually no twist at the junction steps. The 3'-terminal cytosine nucleosides are disordered and there are no electron densities, but the 3' penultimate phosphates are observed. As expected, the wobble pairs are displaced with guanine towards the minor groove and uracil towards the major groove. The largest twist angles (37.70 and 40.57 degrees ) are at steps G1*C17/G2*U16 and U7*G11/C8*G10, while the smallest twist angles (28.24 and 27.27 degrees ) are at G2*U16/G3*C15 and C6*G12/U7*G11 and conform to the pseudo-dyad symmetry of the duplex. The molecule has two unequal kinks (17 and 11 degrees ) at the wobble sites and a third kink at the central G5 site which may be attributed to trans alpha (O5'-P), trans gamma (C4'-C5') backbone conformations. The 2'-hydroxyl groups in the minor groove form inter-column hydrogen bonding, either directly or through water molecules.

Base Pairing↗
PubMed1999

Temporal profile of expression and cellular localization of inducible nitric oxide synthase, interleukin-1beta and interleukin converting enzyme after cryogenic lesion of the rat parietal cortex.

We used in situ hybridization, RT PCR and immunohistochemistry to study the time course of expression and the cellular localization of inducible nitric oxide synthase (iNOS) and interleukin-1beta (IL-1beta) during the first 7 days after induction of a standardized cryogenic lesion on the right parietal cortex in male rats. Cryogenic lesion induced iNOS mRNA in the lesioned hemisphere after 6 to 72 h with a maximum (15+/-2 cells/mm2, n=4, p<0.01 vs. sham) at 24 h. Microglia, invading monocytes and granulocytes in and around the lesion expressed iNOS immunoreactivity starting at 12 h and peaking (29+/-10 cells/mm2, n=4, p<0.05 vs. sham) at 24 h after lesion. Induction of IL-1beta mRNA expression was immediate with a peak (9+/-1 cells/mm2, n=4, p<0.01 vs. sham) at 24 h after cryogenic lesion. The number of round cells with IL-1beta immunoreactivity around the lesion was maximal (8+/-2 cells/0.1 mm2, n=3, p<0.01 vs. sham) at 24 h. A weak astrocytic expression of IL-1beta-immunoreactivity was seen in sham animal brains. Astrocytic IL-1beta-expression was significantly increased in the lesion hemisphere and both hippocampi. Interleukin converting enzyme (ICE) was expressed in astrocytes and microglia around the lesion 6 h after injury. The number of ICE immunoreactive cells (8+/-2 cells/0. 1 mm2, n=3, p<0.05 vs. sham) peaked at 72 h after lesion. Neuronal expression of ICE and IL-1beta was seen in the lesion periphery 72 h and 7 days after injury. At this time, morphological features of apoptosis were evident in cells in the lesion periphery. The data indicate an early activation of microglia and monocyte invasion into the lesion hemisphere leading to multicellular expression of iNOS, ICE, and IL-1beta. These events may contribute to the expansion of neuronal damage after brain injury.

Animals↗
PubMed1999

Mediators of cerebral edema.

The blood-brain barrier (BBB) which is located in the continuous endothelial lining of cerebral blood vessels rigidly controls exchange of water soluble compounds under physiological conditions. Under pathological conditions such as trauma or ischemia, BBB permeability may increase thus allowing plasma constituents to escape into brain tissue. This "opening" of the BBB may, at least in part, be mediated by massive release of autacoids resulting in vasogenic brain edema. Five criteria have to be fulfilled by an individual autacoid to be considered a mediator candidate of cerebral edema: i) a permeability-enhancing action under physiological conditions, ii) a vasodilatory action, iii) the ability to induce vasogenic brain edema, iv) an increase of concentration in the tissue or interstitial fluid under pathological conditions, and v) a decrease of brain edema by specific interference with the release or action of a given autacoid. Among the mediator candidates considered, bradykinin is the only one to meet all criteria. Histamine, arachidonic acid and free radicals including nitric oxide may also be considered mediators of brain edema, but for each of these compounds evidence is less clear than for bradykinin. Although the concept of mediators inducing brain edema is well established by experimental studies, only a bradykinin receptor antagonist has so far gained entrance into clinical evaluation.

Animals↗