Search PubMedSearch

Biomedical subjects

P Barth

Publications and source records attributed to P Barth.

At least 19 recordsLinked to original sources

Tyrosine phosphorylation-dependent suppression of a voltage-gated K+ channel in T lymphocytes upon Fas stimulation.

Selective cell death plays a critical role in the development of the immune system and in the elimination of target cells expressing foreign antigens. Most of programmed cell death occurs by apoptosis. Apoptotic cell death of lymphocytes can be triggered by ligation of APO-1/Fas (CD95) antigen (Suda, T., and Nagata, S. (1994) J. Exp. Med. 179, 873-879; Nagata, S., and Golstein, P. (1995) Science 267, 1449-1456). We find that activation of Fas leads to the inhibition of the voltage-dependent n-type K+ channels (Kv1.3) studied by patch clamp technique in Jurkat T lymphocytes. Tyrosine kinases have been shown to be crucial in Fas-induced cell death (Eischen, C. M., Dick, C. J., and Leibson, P. J. (1994) J. Immunol. 153, 1947-1954). The inhibition of the current is correlated with the tyrosine phosphorylation of immunoprecipitated and blotted K+ channel protein. We show, that the Src-like protein-tyrosine kinase inhibitor herbimycin A and the deficiency of the p56(lck) tyrosine kinase in mutant Jurkat cells abolished the channel inhibition and phosphorylation by anti-Fas antibody, while reconstitution of the p56(lck) kinase partly restored these effects of Fas receptor triggering. These results suggest a regulation of n-type K+ channels by tyrosine kinases upon Fas receptor triggering, which might be important for apoptosis.

Apoptosis

NMR studies on water and polymer diffusion in dextran gels. Influence of potassium ions on microstructure formation and gelation mechanism.

At room temperature aqueous solutions of dextrans with concentrations > 25% (w/w) exhibit a sol-gel transition in the presence of > 1.0 M potassium chloride. In dextrans the gelation was unexpected due to missing anionic groups that usually provide the binding sites for cations. The quantitative investigation of the gel formation is based on changes of the diffusibility of water and dextran chains. The apparent diffusion coefficients of bulk water (in the order of 10(-6) cm2/s) and of water trapped in the junction zones as well as of polymer chains (in the order of 10(-7) to 10(-8) cm2/s) are determined by employing pulsed field gradient stimulated echo (PFGSTE) NMR. The restricted diffusion of bulk water in viscous sols and in soft and rigid gels has been quantitatively analyzed providing data for interbarrier distances (pore size), permeabilities of the diffusion barriers (density of junction zones) and interbarrier diffusion coefficients of water. Based on already published x-ray structure data and in accordance with the diffusion data presented in this paper "potassium-bonding" is assumed to be the most important interaction for the formation of a microstructure and for the stabilization of cross-links. The ionic radius of the potassium ion perfectly fits to the cage established by six oxygen atoms of glucose units of three polymer chains. Other cations, such as Li+, Na+, Rb+ and Cs+, according to their nonfitting ionic radii, do not provoke dextran gelation under these conditions. The mechanism of the transitions from sol to soft gel and further to rigid gel is discussed on the basis of restricted diffusion and x-ray structure data.

Dextrans

Expression of vitamin D receptor in lung cancer.

The active metabolite of vitamin D 1,25-dihydroxycholecalciferol is a hormone-like agent that regulates cell differentiation and proliferation. Various vitamin D derivatives have been shown to induce differentiation in neoplastic cells. The prerequisite for any hormone action is the presence of its receptor. We studied the expression of vitamin D receptor in human lung cancer cell lines and in primary lung cancer tissue. Employing the polymerase chain reaction, 10 out of 11 cell lines stemming from small-cell lung cancer and 15 out of 15 cell lines stemming from non-small-cell lung cancer demonstrated vitamin D receptor expression. An immunohistochemical analysis, using a specific monoclonal antibody, demonstrated vitamin D receptor protein expression in 31 out of 117 (26%) primary small-cell lung cancer cases tested. Positive cells exhibited a nuclear reaction pattern. Twenty-one out of 37 primary non-small-cell lung cancer cases, particularly adenocarcinomas (9/14) and squamous-cell carcinomas (10/15), exhibited vitamin D receptor. Results indicate that a subset of lung cancer cases may be susceptible to the differentiating effects of vitamin D analogues.

Base Sequence

Magic-echo phase-encoding solid imaging with improved time resolution.

The magic-echo phase-encoding solid imaging (MEPSI) sequence is based on the magic-echo pulse sequence for the refocusing of the dipolar interaction and on pure phase-encoding for spatial resolution in all dimensions. MEPSI has many advantages; however, as a consequence of pure phase-encoding, it is very time-consuming. In the following, two strategies are proposed to decrease the time necessary for the acquisition of an image by a factor of 2 per dimension.

Magnetic Resonance Spectroscopy

Aging of polymer networks as studied by material property NMR imaging.

Relaxation-weighted NMR imaging is a powerful tool for the investigation of aging processes in rubber networks, in particular if it is combined with a theoretical description to relate the NMR data with suitable parameters of the material. Following this concept, spin-spin relaxation decays in rubber samples, consisting of differently aged pieces of natural rubber have been acquired in a spatially resolved experiment. The data were evaluated using a dynamical model and transformed into images of those material properties, which are affected by the aging process. Images representing the crosslink density and the correlation times, which characterize the polymer chain dynamics, have been calculated. The differently aged rubber pieces can be easily discriminated in such material property (MAP) images.

Magnetic Resonance Spectroscopy

Lung surfactant components in bronchoalveolar lavage after inhalation of NO2 as markers of altered surfactant metabolism.

To study the effects of nitrogen dioxide (NO2) inhalation on lung lavage surfactant components as markers of an altered surfactant metabolism in type II pneumocytes, rats were exposed to atmospheres with increasing NO2 concentrations (0.8, 5.0, and 10.0 ppm) over 1 and 3 days. After exposure lung lavage was performed and surfactant components as well as lavageable cells analyzed. An increased number of total lavage cells was found with increasing concentration and duration of NO2 exposure. Cell distribution showed an elevation in the number of granulocytes and lymphocytes whereas the number of macrophages was diminished. The amount of total lavage protein revealed an increase related to NO2 concentration and duration. Also the content of lavage phospholipid was increased, with a decreased portion of phosphatidylcholine (PC). Further analyses of PC showed a diminished composition of saturated fatty acids but an elevated content of the unsaturated portion. Functional studies on surfactant phospholipid extracts exhibited comparable values for the surface tension at equilibrium, as well as for the maximal and minimal surface tension of animals exposed to 0.8 ppm NO2 and controls. Higher NO2 concentrations (5 and 10 ppm) resulted in increased values for surface tension compared to controls. This was also observed with purified surfactant that was obtained from controls and from NO2-exposed rats. These experiments show that in vitro exposure of purified surfactant to NO2 atmospheres was more effective than exposure in vivo. When the structure of the surfactant proteins A was studied it was found not to be altered by the NO2. The data clearly demonstrate that NO2 inhalation impaired function of surfactant components that may be used as markers of altered surfactant metabolism.

Animals

[Nematode larva migrans. On two cases of filarial infection].

With rapid air travel, so-called parasitic infections are becoming more important in northern hemisphere and temperate climates. Parasitic disease is usually taken to imply infections caused by protozoa and helminths. The most important helminthic infections in man and with world-wide incidence are schistosomiasis, hookworm, and filariasis. We report the clinico-pathological findings of two patients with filarial infection of soft tissue and lymphatic nodes.

Adult

Tumor-forming eosinophilic cystitis in children. Case report and review of literature.

Eosinophilic cystitis is an unusual bladder lesion of unclear etiology first described in 1960. It usually causes irritative voiding symptoms and hematuria and in its rare tumor-like appearance the disease may mimic an invasive bladder neoplasm. In the report herein, a case of an 11-year-old boy with a tumor-forming eosinophilic cystitis is presented which was mistaken for an infiltrative vesical malignancy until the histopathological study was completed. The principal clinical findings, differential diagnosis, etiology, pathogenesis and treatment modalities of this inflammatory disease are discussed.

Child

Spontaneous splenic rupture in acute myeloid leukemia: sonographic follow-up study.

We report on a 52-year-old patient with acute myeloid leukemia. After induction chemotherapy, routine ultrasound displayed a round focal hyperechoic intrasplenic lesion. Tumor was primarily misdiagnosed for splenic hemangioma. Diagnosis of spontaneous progredient splenic rupture was made by color-coded Doppler sonography, sonographic follow-up examinations and confirmed by splenectomy for final treatment. No trauma was found.

Diagnosis, Differential

Sequence of pig lens aldose reductase and electrospray mass spectrometry of non-covalent and covalent complexes.

The complete sequence of pig lens aldose reductase (EC 1.1.1.21), a member of the nicotinamide coenzyme-dependent aldo-keto reductase super family, was determined by the combined use of data obtained from Edman degradation, fast-atom-bombardment mass spectrometry and electrospray mass spectrometry. The N-terminal residue of human and pig aldose reductase was shown to be acetylated. The assignment of a disulfide bridge (Cys298-Cys303) was obtained by mass spectrometry. Electrospray mass spectrometry has been used for molecular mass measurement of human muscle (35758 +/- 7 Da) and pig lens (35778 +/- 3Da) aldose reductase; using mild ionization conditions, it has also been used to study the reversible interaction involved in a non-covalent complex with NADP+ (36527 +/- 4Da). An alkylating analog of NADP+ (3-chloroacetylpyridine-adenine dinucleotide phosphate) was used as an irreversible inhibitor to investigate the NADP binding site and the mass of the covalent complex was measured (36521 +/- 3 Da).

Aldehyde Reductase

[N-acetylcysteine decreases functional and structural, ARDS-typical lung changes in endotoxin-treated rats].

Oxygen radicals and oxygen radical mediators derived from activated granulocytes are important components in the development of acute lung injury, namely the adult respiratory distress syndrome ARDS. N-acetylcysteine (NAC) is one important substance for endogenous production of reduced glutathion, which is known to be an intra- and extracellular reducing agent also found in lung tissue. We evaluated the effect of exogenous NAC on the endotoxin induced development and course of ARDS in rats. ARDS-like injury was induced in rats via intraperitoneal injection of Salmonella enteritidis endotoxin 30 mg/kg body weight. NAC or solvent was injected intraperitoneally 30 min prior to, at the time of and 30 min after injection of endotoxin respectively with 150 mg/kg body weight each dose. Endotoxin injection in rats resulted in 80% mortality within 72 hours, increased lung wet weight, severe ultrastructural lung damage as measured by histological methods. In isolated, ventilated, with physiological salt solution perfused rat lungs vasocontractility was severely blunted, lung albumin leakage was increased, thromboxane B2 (TXB2) and 6-keto-prostaglandin-F1 alpha (6-keto-PGF1 alpha) perfusate levels were increased. NAC treatment significantly improved survival of endotoxin treated rats, ameliorated structural lung damage, diminished lung wet weight and lung albumin leakage, lowered lung perfusate TXB2 and 6-keto-PGF1 alpha levels and slightly improved vasocontractility in isolated perfused lungs. Therefore, NAC significantly ameliorates ARDS-like lung injury in rats, when given in vivo.

Acetylcysteine

A case of symptomatic hemidystonia improved by ventroposterolateral thalamic electrostimulation.

A 16-year-old boy presented with a left anterothalamic lesion secondary to an extradural hematoma. A few months later, a right hemidystonia developed. The dystonic posture, which predominated in the right hand, was not associated with any motor deficit or sensory loss. Superficial sensory stimulation of the right palm and forearm and proprioceptive stimuli induced by passive movements of the right thumb decreased the dystonic posture. Electrical stimulation of the left ventroposterolateral nucleus of the thalamus induced a dramatic improvement in the dystonic postures and movement of the upper right limb. This finding suggests that the role of tactile and proprioceptive stimulation should be analyzed in patients presenting with a symptomatic hemidystonia. When such sensory stimulation is effective, thalamic stimulation may be tried in patients whose condition is incapacitating.

Adolescent

Impaired regulation of surfactant phospholipid metabolism in the isolated rat lung after nitrogen dioxide inhalation.

Various drugs have been shown to stimulate surfactant phospholipid metabolism. Particularly beta-adrenergic agonists play an important role under physiologic conditions. For the first time we have studied whether nitrogen dioxide (NO2) inhalation alters beta-adrenergic regulation of surfactant phospholipid metabolism in the model of the isolated lung. Rats were continuously exposed in vivo to a 5 ppm NO2-containing atmosphere for 48 hr. The lungs were isolated and perfused in presence of the beta-adrenergic agonist dopexamine and surfactant metabolism was studied in three lung compartments: (1) lung lavage, (2) lung tissue, and (3) lavagable free alveolar cells. We found that (1) in normal rat lungs dopexamine increased the incorporation of palmitate and choline from the perfusate into lung lavage phospholipids. In nitrogen dioxide exposed rat lungs beta-adrenergic stimulation did not cause an increase in precursor incorporation. No significant difference in unstimulated precursor incorporation was found for normal and NO2-exposed rat lungs. (2) Lung tissue from rats exposed to NO2 showed a decreased precursor incorporation into disaturated phosphatidylcholine due to an augmented cellular pool size. (3) Lavagable alveolar cells showed an increased palmitate uptake after nitrogen dioxide inhalation and by beta-adrenergic stimulation. From these data we conclude that nitrogen dioxide inhalation impairs the beta-adrenergic regulation of surfactant phospholipid metabolism. Moreover these data underline the importance of beta-adrenergic agonists in surfactant metabolism.

Administration, Inhalation

GLP-1 stimulates secretion of macromolecules from airways and relaxes pulmonary artery.

Recent data revealed the existence of specific receptors for glucagon-like peptide-1(7-36)amide (GLP-1) on rat lung membranes. Utilizing slide-mount autoradiography of fresh frozen lung tissue sections, we have localized binding sites for GLP-1 on mucous glands in the trachea and on vascular smooth muscle of the pulmonary artery. When tracheas were incubated in a modified Ussing chamber, the addition of GLP-1 to the submucosal side increased 35S-sulfate-labeled macromolecule secretion (191 +/- 12% above basal, P < 0.005). The optimal secretory response elicited by GLP-1 was approximately 23% of the maximal secretory response after a maximal acetylcholine stimulation. Other proglucagon-derived peptides such as glucagon, oxyntomodulin, and GLP-2 had no effect. In isolated rings of arteries, GLP-1 (10(-8) to 10(-5) M) induced a dose-dependent and time-reversible relaxation of preconstricted arteries. In a preparation with denuded epithelium, GLP-1 lost its effect. In conclusion, GLP-1 might represent another neuropeptide that acts as neurotransmitter of the peptidergic, nonadrenergic-noncholinergic nervous system that innervates the airways.

Animals