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Biomedical subjects

A Klein

Publications and source records attributed to A Klein.

At least 55 records · Page 3Linked to original sources
PubMed2003

[Automated hearing threshold estimation in newborns using extrapolated DPOAE input/output functions].

BACKGROUND AND AIM: A new method for automatically assessing hearing loss by means of extrapolated DPOAE I/O-functions was applied for the first time in newborns. METHODS: DPOAE I/O-functions were recorded in 118 ears of 93 newborns (mean age 3 days) at 12 frequencies between 1 and 8 kHz. L(2) was varied between 20 and 65 dB SPL with L(1)=0.4L(2)+39 and f(2)/f(1)=1.2. Auditory thresholds were constructed using the estimated DPOAE threshold level from extrapolated DPOAE I/O-functions. Follow-up measurements were conducted in 15 ears 4 weeks later. RESULTS: The first measurement revealed a high-frequency hearing loss. The second measurement showed normal hearing function. This fact and the decrease of DPOAE level in the frequency range of the hearing loss, while keeping the compressive shape of the DPOAE I/O-functions, indicate that transitory sound conduction disturbance may be due to amniotic fluid. CONCLUSIONS: The method fulfils the essential criteria for screening newborn hearing. It is fast and easy to handle, and measurement and data analysis are performed automatically. Preliminary results suggest that the new method is able to differentiate between transitory middle-ear dysfunction and persisting cochlear disorders. Due to its better diagnostic capabilities in comparison to TEOAE, DPOAE, and FAEP, this method may provide a new instrument with which to make a fast evaluation of hearing function in children.

Acoustic Stimulation↗
PubMed2003

Photoproduction of the omega meson on the proton at large momentum transfer.

The differential cross section, dsigma/dt, for omega meson exclusive photoproduction on the proton above the resonance region (2.6<W<2.9 GeV) was measured up to a momentum transfer -t=5 GeV2 using the CLAS detector at Jefferson Laboratory. The omega channel was identified by detecting a proton and pi(+) in the final state and using the missing mass technique. While the low momentum transfer region shows the typical diffractive pattern expected from Pomeron and Reggeon exchange, at large -t the differential cross section has a flat behavior. This feature can be explained by introducing quark interchange processes in addition to the QCD-inspired two-gluon exchange.

Journal Article↗
PubMed2003

Somatostatin analogue scintigraphy in Merkel cell tumours.

BACKGROUND: Merkel cell tumours are rare neoplasms of the skin with frequent regional and distant metastases. Scintigraphy with the radiolabelled somatostatin analogue octreotide is a possible method for in vivo localization of the primary tumour and its metastases. OBJECTIVES: To estimate the diagnostic value of indium (111) -octreotide scintigraphy (Octreoscan in detecting metastases. METHODS: Scans of 11 patients with Merkel cell carcinoma were evaluated, in whom scintigraphy was performed in addition to the conventional investigations, chest X-ray, ultrasonography and computed tomography (CT). RESULTS: In four cases metastases were found both by scintigraphy and by conventional methods; two investigations showed a suspicious accumulation of radioactivity on scintigraphy that could not be confirmed by CT and clinical progression. In three cases CT-verified metastases were not found by scintigraphy. Two patients were found to be tumour free, i.e. free of metastases by scintigraphy and conventional methods, indicating true-negative results. CONCLUSION: These data confirm that scintigraphy with the radiolabelled somatostatin analogue octreotide is not clinically helpful in detecting metastases from Merkel cell carcinoma. In this relatively small sample the method generated false-positive or false-negative results in five of 11 cases.

Aged↗
PubMed2003

Catalepsy intensifies context-dependently irrespective of whether it is induced by intermittent or chronic dopamine deficiency.

It is well known that neuroleptic-induced catalepsy in rats intensifies upon repeated testing. Here, the question is addressed whether intensification of catalepsy results from intermittent drug administration or from intermittent context exposure. In experiment 1, rats were treated with intermittent haloperidol injections (0.25 mg/kg) followed by the catalepsy test (descent latency from the horizontal bar). In experiment 2, rats were lesioned with 6-hydroxydopamine injections into the striatum, resulting in a 45% reduction of dopamine concentration. Catalepsy was tested intermittently for several weeks. In both experiments we found a very stable intensification of catalepsy over 9 (haloperidol rats) and 11 (lesioned rats) days, showing that intensification is not due to intermittent dopamine depletion. In both experiments, intensification of catalepsy was very stable and was observed 18 days later in haloperidol-treated rats and 101 days later in lesioned animals. However, a change of the environmental context abolished the intensified catalepsy in both experiments. It is concluded that intensification of catalepsy is due to intermittent context exposure rather than intermittent drug administration. It is generally accepted that 6-hydroxydopamine lesions represent an animal model of Parkinson's disease. Given the results above, context-dependent intensification of parkinsonian symptoms might also occur in Parkinson's disease, and its prevention should be taken into consideration for future therapy of the disease.

Animals↗
PubMed2002

The effects of ethanol on the glycosylation of human transferrin.

Appearance of a hyposialylated transferrin fraction in the plasma during chronic alcohol exposure is a well-known phenomenon, and it represents the best available marker of chronic alcohol consumption. The mechanisms of its appearance are still not well understood and are extremely complex, involving biosynthesis and catabolism alterations, although the only structural abnormality described corresponds to the loss of an entire glycan chain. We analyzed and compared the oligosaccharides present on the different isoforms of purified transferrin isolated from control and patients with severe alcohol abuse by fluorescent carbohydrate electrophoresis and matrix-assisted laser desorption ionization mass spectrometry. Our data indicate that the major modification observed is the loss of an entire oligosaccharide chain; we also demonstrate that there is a modification of terminal sialylation. Carbohydrate-deficient transferrin (CDT) is the result of multiple alterations of glycosylation. These results give a partial explanation to the poor sensitivity of the measurement of CDT and its controversial use as a marker of chronic alcohol consumption.

Alcoholism↗
PubMed2002

Eta photoproduction on the proton for photon energies from 0.75 to 1.95 GeV.

Differential cross sections for gammap-->etap have been measured with tagged real photons for incident photon energies from 0.75 to 1.95 GeV. Mesons were identified by missing mass reconstruction using kinematical information for protons scattered in the production process. The data provide the first extensive angular distribution measurements for the process above W=1.75 GeV. Comparison with preliminary results from a constituent quark model support the suggestion that a third S11 resonance with mass approximately 1.8 GeV couples to the etaN channel.

Journal Article↗
PubMed2002

Q2 Dependence of quadrupole strength in the gamma*p --> Delta(+)(1232) --> p pi(0) transition.

Models of baryon structure predict a small quadrupole deformation of the nucleon due to residual tensor forces between quarks or distortions from the pion cloud. Sensitivity to quark versus pion degrees of freedom occurs through the Q2 dependence of the magnetic (M1+), electric (E1+), and scalar (S1+) multipoles in the gamma*p-->Delta(+)-->p pi(0) transition. We report new experimental values for the ratios E(1+)/M(1+) and S(1+)/M(1+) over the range Q2 = 0.4-1.8 GeV2, extracted from precision p(e,e(')p)pi(0) data using a truncated multipole expansion. Results are best described by recent unitary models in which the pion cloud plays a dominant role.

Journal Article↗
PubMed2002

dpp genes of Rhizobium leguminosarum specify uptake of delta-aminolevulinic acid.

An operon with homology to the dppABCDF genes required to transport dipeptides in bacteria was identified in the N2-fixing symbiont, Rhizobium leguminosarum. As in other bacteria, dpp mutants were severely affected in the import of delta-aminolevulinic acid (ALA), a heme precursor. ALA uptake was antagonized by adding dipeptides, indicating that these two classes of molecule share the same transporter. Mutations in dppABCDF did not affect symbiotic N2 fixation on peas, suggesting that the ALA needed for heme synthesis is not supplied by the plant or that another uptake system functions in the bacteroids. The dppABCDF operon of R. leguminosarum resembles that in other bacteria, with a gap between dppA and dppB containing inverted repeats that may stabilize mRNA and may explain why transcription of dppA alone was higher than that of dppBCDF. The dppABCDF promoter was mapped and is most likely recognized by sigma70.

Aminolevulinic Acid↗
PubMed2002

Pulmonary eosinophilia in a murine model of allergic inflammation is attenuated by small molecule alpha4beta1 antagonists.

Inhibition of alpha4beta1/vascular cell adhesion molecule-1 (VCAM-1) interactions have therapeutic potential in treating allergic airway disease because of the importance of these adhesion molecules in the trafficking of eosinophils, lymphocytes, and monocytes. We examined several small molecule inhibitors of alpha4beta1/VCAM-1 interactions with in vitro potencies (IC(50) values) ranging from 0.52 nM (CP-664511; 3-[3-(1-[2-[3-methoxy-4-(3-O-tolyl-ureido)phenyl]-acetylamino]-3-methyl-butyl)isoxazol-5-yl]-propionic acid) to 38.5 nM (CP-609643; 3-[3-methyl-1-[2-[4-(3-O-tolyl-ureido)-phenyl]-acetylamino]-butyl)-isoxazol-5-yl]-propionic acid). The same compounds were evaluated in vivo using a murine model of ovalbumin-induced pulmonary eosinophilia. In this model, systemic administration of antibodies against alpha4 reduced bronchoalveolar lavage (BAL) eosinophilia approximately 60%. Small molecule alpha4beta1 antagonists were administered by intratracheal instillation and demonstrated dose-dependent inhibition of BAL eosinophil numbers and achieved a maximum inhibition of approximately 60%. In general, the rank order of potency for these compounds in vitro was consistent with that observed in vivo, which confirms that their efficacy is likely via blockade of alpha4beta1/VCAM-1 interactions. The most potent compound, CP-664511, also inhibited BAL eosinophilia following s.c. administration (1-10 mg/kg, s.c.). These data support the utility of small molecule alpha4beta1 antagonists in the treatment of relevant diseases, such as asthma.

Animals↗
PubMed2002

Leukotriene B(4) induces nitric oxide synthesis in Trypanosoma cruzi-infected murine macrophages and mediates resistance to infection.

The production of nitric oxide (NO) by gamma interferon (IFN-gamma)-activated macrophages is a major effector mechanism during experimental Trypanosoma cruzi infection. In addition to IFN-gamma, chemoattractant molecules, such as platelet-activating factor (PAF) and CC chemokines, may also activate macrophages to induce NO and mediate the killing of T. cruzi in an NO-dependent manner. Here we investigated the ability of leukotriene B(4) (LTB(4)) to induce the production of NO by macrophages infected with T. cruzi in vitro and whether NO mediated LTB(4)-induced parasite killing. The activation of T. cruzi-infected but not naive murine peritoneal macrophages with LTB(4) induced the time- and concentration-dependent production of NO. In addition, low concentrations of LTB(4) acted in synergy with IFN-gamma to induce NO production. The NO produced mediated LTB(4)-induced microbicidal activity in macrophages, as demonstrated by the inhibitory effects of an inducible NO synthase inhibitor. LTB(4)-induced NO production and parasite killing were LTB(4) receptor dependent and were partially blocked by a PAF receptor antagonist. LTB(4) also induced significant tumor necrosis factor alpha (TNF-alpha) production, and blockade of TNF-alpha suppressed LTB(4)-induced NO release and parasite killing. A blockade of LTB(4) or PAF receptors partially inhibited IFN-gamma-induced NO and TNF-alpha production but not parasite killing. Finally, daily treatment of infected mice with CP-105,696 was accompanied by a significantly higher level of blood parasitemia, but not lethality, than that seen in vehicle-treated animals. In conclusion, our results suggest a role for LTB(4) during experimental T. cruzi infection. Chemoattractant molecules such as LTB(4) not only may play a major role in leukocyte migration into sites of inflammation in vivo but also, in the event of an infection, may play a relevant role in the activation of recruited leukocytes to kill the invading microorganism in an NO-dependent manner.

Animals↗
PubMed2002

[Magnetoneurographic registration of evoked summation action fields over lumbar vertebrae following transcutaneous tibial nerve stimulation].

Goal of this study was the development of a protocol for the registration of evoked magnetic fields over the lumbar spine using off-the-shelf equipment. Three subjects in a sitting position with their torso bent slightly forward were stimulated at the tibial nerve with a commercially available stimulator. Neuromagnetic fields were registered over a circular, 800 cm2 area of the lumbosacral spine using a 61-channel 4D-Neuroimaging biomagnetometer. After appropriate signal processing, dipolar magnetic fields with a field strength 5-17 fT peak-to-peak amplitude were detected in three out of four registrations. Location and orientation of these fields concurred with the expected evoked compound action currents along the course of the nerve fibers.

Adult↗
PubMed2001

Photoproduction of the rho(0) meson on the proton at large momentum transfer.

The differential cross section, d sigma/dt, for rho(0) meson photoproduction on the proton above the resonance region was measured up to a momentum transfer -t = 5 GeV2 using the CLAS detector at the Thomas Jefferson National Accelerator Facility. The rho(0) channel was extracted from the measured two charged-pion cross sections by fitting the pi(+)pi(-) and p pi(+) invariant masses. The low momentum transfer region shows the typical diffractive pattern expected from Reggeon exchange. The flatter behavior at large -t cannot be explained solely in terms of QCD-inspired two-gluon exchange models. The data indicate that other processes, like quark interchange, are important to fully describe rho photoproduction.

Journal Article↗
PubMed2001

Overexpression of laminin alpha1 chain in colonic cancer cells induces an increase in tumor growth.

Laminins represent a growing family of glycoproteins constituting the basement membrane. They are known to direct many biological processes. With respect to carcinogenesis, laminins play an important role in cell adhesion, mitogenesis, differentiation and even metastasis. To further study the biological significance of laminin-1 (composed of alpha1, beta1 and gamma1 chains) in intestinal cell differentiation or tumorigenesis, an alpha1-laminin expression vector was introduced into the HT29 colonic cancer cells, in which laminin alpha1 chain is not expressed. Upon transfection of the alpha1 chain, the alpha1beta1gamma1 trimer was found secreted in the media along with free alpha1 chain as assessed by immunoprecipitation. The presence of the laminin alpha1 chain did not significantly modify the levels of the other laminin chains nor the integrins expressed by the HT29 cells. In spite of similar growth properties with the control cells in vitro (plastic dish, soft agar), the laminin alpha1 transfectants showed a significantly increased tumor growth when injected in nude mice. Histologic and immunohistochemic examination of the laminin alpha1-expressing tumors points to an increased recruitment of the host stromal and vascular cells, without modification in the differentiation profile and invasion potential. In parallel, a clear accumulation of laminin-10 (alpha5beta1gamma1) at the carcinoma/stromal interface and a segregation of the integrin beta4 subunit at the basal pole of the cancer cells occurred, compared to control tumors. Overall, our observations emphasize the importance of laminin-1 as a chemoattractant of both stromal and vascular cells and in epithelial/stromal cell interactions for the organization of the basement membrane and segregation of integrins leading to an epithelial cell growth signal. Such a sequence of events is reminiscent of what occurs during development.

Animals↗
PubMed2001

Stem cell factor-induced leukotriene B4 production cooperates with eotaxin to mediate the recruitment of eosinophils during allergic pleurisy in mice.

The understanding of the mechanisms underlying eosinophil recruitment in vivo may aid in the development of novel strategies for the treatment of allergic disorders. In this study, we investigated the role of chemokines in the cascade of events leading to eosinophil recruitment in a stem cell factor (SCF)- and leukotriene B(4) (LTB(4))-dependent allergic pleurisy model in mice. The intrapleural administration of the eosinophil-active chemokines eotaxin, RANTES, and macrophage-inflammatory protein 1alpha (MIP-1alpha) induced a time- and dose-dependent eosinophil recruitment. Pretreatment with anti-eotaxin, but not anti-RANTES or anti-MIP-1alpha, blocked the recruitment of eosinophils following Ag challenge of sensitized animals, and significant eotaxin immunoreactivity was detected in the pleural cavity of these animals. Similarly, only the anti-eotaxin inhibited the eosinophil recruitment induced by injection of SCF in naive animals. However, blockade of SCF did not inhibit the release of eotaxin after Ag challenge of sensitized mice. Akin to its effects on SCF and in the allergic reaction, eotaxin-induced eosinophil recruitment was blocked by the LTB(4) receptor antagonist CP105696. Nevertheless, SCF, but not eotaxin, appeared to regulate the endogenous release of LTB(4) after Ag challenge. Finally, we show that low doses of eotaxin synergized with LTB(4) to induce eosinophil recruitment in the pleural cavity. Overall, the present results show that eotaxin and SCF-induced LTB(4) cooperate to induce eosinophil recruitment into sites of allergic inflammation. Cooperation between inflammatory mediators must be an important phenomenon in vivo, explaining both the ability of lower concentrations of mediators to induce a full-blown functional response and the effectiveness of different strategies at inhibiting these responses.

Animals↗