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Biomedical subjects

P Beck

Publications and source records attributed to P Beck.

At least 37 records · Page 2Linked to original sources
PubMed2000

Concurrent enteric helminth infection modulates inflammation and gastric immune responses and reduces helicobacter-induced gastric atrophy.

Helicobacter pylori is causally associated with gastritis and gastric cancer. Some developing countries with a high prevalence of infection have high gastric cancer rates, whereas in others, these rates are low. The progression of helicobacter-induced gastritis and gastric atrophy mediated by type 1 T-helper cells may be modulated by concurrent parasitic infection. Here, in mice with concurrent helminth infection, helicobacter-associated gastric atrophy was reduced considerably despite chronic inflammation and high helicobacter colonization. This correlated with a substantial reduction in mRNA for cytokines and chemokines associated with a gastric inflammatory response of type 1 T-helper cells. Thus, concurrent enteric helminth infection can attenuate gastric atrophy, a premalignant lesion.

Animals↗
PubMed2000

Activation of natural killer T cells by alpha-galactosylceramide in the presence of CD1d provides protection against colitis in mice.

BACKGROUND & AIMS: CD1d is a major histocompatibility complex class I-like molecule that presents glycolipid antigens to a subset of natural killer (NK)1.1(+) T cells. These NK T cells exhibit important immunoregulatory functions in several autoimmune disease models. METHODS: To investigate whether CD1d and NK T cells have a similar role in intestinal inflammation, the effects of the glycolipid, alpha-galactosylceramide (alpha-GalCer), on dextran sodium sulfate (DSS)-induced colitis were examined. Wild-type (WT), CD1d(-/-), and RAG(-/-) mice were examined for their response to either alpha-GalCer or the control analogue, alpha-mannosylceramide (alpha-ManCer). RESULTS: WT mice, but not CD1d(-/-) and RAG(-/-) mice, receiving alpha-GalCer had a significant improvement in DSS-induced colitis based on body weight, bleeding, diarrhea, and survival when compared with those receiving alpha-ManCer. Elimination of NK T cells through antibody-mediated depletion resulted in a reduction of the effect of alpha-GalCer. Furthermore, adoptive transfer of NK T cells preactivated by alpha-GalCer, but not alpha-ManCer, resulted in diminished colitis. Using a fluorescent-labeled analogue of alpha-GalCer, confocal microscopy localized alpha-GalCer to the colonic surface epithelium of WT but not CD1d(-/-) mice, indicating alpha-GalCer binds CD1d in the intestinal epithelium and may be functionally active at this site. CONCLUSIONS: These results show an important functional role for NK T cells, activated by alpha-GalCer in a CD1d-restricted manner, in regulating intestinal inflammation.

Animals↗
PubMed2000

European measurements of aircraft crew exposure to cosmic radiation.

For more than 5 y, the European Commission has supported research into scientific and technical aspects of cosmic-ray dosimetry at flight altitudes in civil radiation. This has been in response to legislation to regard exposure of aircraft crew as occupational, following the recommendations of the International Commission on Radiological Protection in Publication 60. The response to increased public interest and concern, and in anticipation of European and national current work, within a total of three multi-national, multi-partner research contracts, is based on a comprehensive approach including measurements with dosimetric and spectrometric instruments during flights, at high-mountain altitudes, and in a high-energy radiation reference field at CERN, as well as cosmic-ray transport calculations. The work involves scientists in the fields of neutron physics, cosmic-ray physics, and general dosimetry. A detailed set of measurements has been obtained by employing a wide range of detectors on several routes, both on subsonic and supersonic aircraft. Many of the measurements were made simultaneously by several instruments allowing the intercomparison of results. This paper presents a brief overview of results obtained. It demonstrates that the knowledge about radiation fields and on exposure data has been substantially consolidated and that the available data provide an adequate basis for dose assessments of aircraft crew, which will be legally required in the European Union after 13 May 2000.

Aircraft↗
PubMed1999

Gamma-hydroxybutyrate is a weak agonist at recombinant GABA(B) receptors.

Gamma-hydroxybutyrate (GHB) is a neuromodulator with high affinity binding sites in the mammalian brain. However, the receptor for GHB has not yet been identified. There are indications that GHB and gamma-aminobutyric acid (GABA) mediate their effects via the same receptor. We tested this hypothesis using GABA(B)R1/R2 receptors co-expressed with Kir3 channels in Xenopus oocytes. GHB activated these receptors with an EC50 of approximately 5 mM and a maximal stimulation of 69% when compared to the GABA(B) receptor agonist L-baclofen. GHB and L-baclofen did not amplify each others effect nor did they stimulate the GABA(B) receptor in a linearly additive manner. CGP54626A, 2-OH saclofen and CGP35348, three competitive GABA(B) receptor antagonists, inhibited the GHB induced response completely. A concentration of 30 mM GHB displaced [125I]CGP64213 binding at GABA(B)R1 expressed in COS cells by 21%. These results indicate that GHB is a weak partial agonist at the GABA binding site of GABA(B)R1/R2.

Anesthetics, Intravenous↗
PubMed1999

The use of TEPC for reference dosimetry.

The radiation fields on board aircraft are quite complex and cover an energy range that is unusual in ordinary radiation protection work. Usually dosemeters measure only one radiation quality and the mixture found on board makes measurements complicated. There is also some doubt when it comes to the best choice of quantity for this application and no radiation standards exist for this kind of radiation field. For those reasons there is a need to find a standard measurement procedure that could serve as a reference for other, maybe simpler, measurements or for calculations of route doses. The only direct reading dosemeter that both measures the absorbed dose to tissue and the radiation quality (in terms of lineal energy) is the tissue-equivalent proportional counter (TEPC). The instrument was originally developed for scientific purposes and is still used as such. The detector consists of a gas filled cavity surrounded by a few mm thick wall. Both wall and gas consists of tissue-like material. The measurement principles are explained. Results observed with TEPC instruments are demonstrated. A preliminary collection of data reported by different groups from measurements on board aircraft will be shown. The results agree within +/- 20%. The conclusion is that TEPC instruments have the capacity of serving as reference instruments.

Aerospace Medicine↗
PubMed1998

GABA(B)-receptor subtypes assemble into functional heteromeric complexes.

B-type receptors for the neurotransmitter GABA (gamma-aminobutyric acid) inhibit neuronal activity through G-protein-coupled second-messenger systems, which regulate the release of neurotransmitters and the activity of ion channels and adenylyl cyclase. Physiological and biochemical studies show that there are differences in drug efficiencies at different GABA(B) receptors, so it is expected that GABA(B)-receptor (GABA(B)R) subtypes exist. Two GABA(B)-receptor splice variants have been cloned (GABA(B)R1a and GABA(B)R1b), but native GABA(B) receptors and recombinant receptors showed unexplained differences in agonist-binding potencies. Moreover, the activation of presumed effector ion channels in heterologous cells expressing the recombinant receptors proved difficult. Here we describe a new GABA(B) receptor subtype, GABA(B)R2, which does not bind available GABA(B) antagonists with measurable potency. GABA(B)R1a, GABA(B)R1b and GABA(B)R2 alone do not activate Kir3-type potassium channels efficiently, but co-expression of these receptors yields a robust coupling to activation of Kir3 channels. We provide evidence for the assembly of heteromeric GABA(B) receptors in vivo and show that GABA(B)R2 and GABA(B)R1a/b proteins immunoprecipitate and localize together at dendritic spines. The heteromeric receptor complexes exhibit a significant increase in agonist- and partial-agonist-binding potencies as compared with individual receptors and probably represent the predominant native GABA(B) receptor. Heteromeric assembly among G-protein-coupled receptors has not, to our knowledge, been described before.

Amino Acid Sequence↗
PubMed1998

[Intravascular lymphomatosis (angiotrophic large-cell lymphoma), a rare differential diagnosis in painful swelling of the leg with treatment-resistant fever].

HISTORY AND CLINICAL FINDINGS: For one month a 69-year-old woman had been suffering from increasingly painful and reddened swelling of both legs and induration of the skin of the left thigh, about 15 cm in diameter. In addition she had fever and rigors. Antibiotic treatment, begun because erysipelas was suspected, was ineffective and she was hospitalized. Although obese she was in a good general condition with no obvious abnormalities on routine lung, heart and neurological examination. No lymph nodes were palpated. INVESTIGATIONS: Laboratory tests showed increased inflammatory parameters, marked rise in lactate dehydrogenase and a normochromic anaemia, hemoglobin of 9.5 g/dl. Doppler sonography excluded deep vein thrombosis, but marked chronic venous insufficiency was revealed. Extensive tests, including soft-tissue sonography, radiology and skin biopsy failed to establish a diagnosis. TREATMENT AND CAUSE: Antibiotic treatment was resumed because a diagnosis of only partly treated erysipelas was made. But several changes to a variety of antibiotics remained ineffective. Collagen disease was excluded by the biochemical and biopsy results. As the skin changes in both legs increased a skin and muscle biopsy from the indurated area of the left thigh was done: it showed intravascular large-cell lymphomatosis. A search for a paraneoplastic process revealed an adenocarcinoma of the ascending colon that was successfully resected. The patient died before the planned chemotherapy could be initiated. CONCLUSION: In case of treatment-resistant fever associated with painful swelling of the leg and skin changes of unknown etiology a deep skin biopsy should be an early consideration to exclude such causes as lymphoma, including the very rare intravascular clear-cell lymphomatosis.

Adenocarcinoma↗
PubMed1998

Augmented interleukin-1beta-induced depression of locomotor activity in cholestatic rats.

"Sickness behaviors" such as lethargy, fatigue, and malaise occur commonly in patients with cholestatic liver diseases and contribute significantly to the morbidity associated with these diseases. However, the cause of these symptoms is unknown. Interleukin-1beta (IL-1beta) released within the brain has been implicated in the genesis of a number of "sickness behaviors," including malaise and lethargy. Therefore, we investigated whether experimental cholestatic liver disease caused by bile duct resection (BDR) in rats is associated with enhanced central sensitivity to IL-1beta-induced "sickness behaviors." The central infusion of IL-1beta at a dose that produced an insignificant decrease in locomotor activity in control rats produced a striking reduction in locomotor activity in cholestatic rats. The anorectic response to central IL-1beta infusion was similar in cholestatic and noncholestatic animals and did not parallel our locomotor activity findings. Therefore, cholestatic liver injury is characterized by augmented central responsiveness to IL-1beta with respect to a decrease in locomotor activity. These findings may explain, at least in part, the high incidence of symptoms such as fatigue, malaise, and lethargy that occur in cholestatic patients and may open novel future avenues for their treatment.

Animals↗
PubMed1997

Differential effects of endothelin receptor activation on cyclic flow variations in rat mesenteric arteries.

BACKGROUND: Cyclic flow variations (CFVs) represent repetitive cycles of platelet adherence-aggregation and vasoconstriction, followed by dislodgment of platelet thrombi and restoration of blood flow at the site of vascular injury. Although activation of endothelin A (ETA) and endothelin B (ETB) receptors leads to vasoconstriction and nitric oxide release, respectively, the roles of endogenous endothelin-1 (ET-1) and its receptors in CFVs are unknown. METHODS AND RESULTS: A side branch of a mesenteric artery of male Wistar rats was cannulated and a short segment of the artery was mechanically injured to induce CFVs. After 20 minutes of saline infusion, either saline (negative control), BQ-123 (ETA receptor antagonist, 10 microg/min), BQ-788 (ETB receptor antagonist, 10 microg/min), or sarafotoxin S6c (ETB receptor agonist, 10 ng/min) was infused for 20 minutes from the side branch into the injured arterial segment. Percent (%) luminal stenosis as well as proximal and distal vessel diameters were observed and quantitatively measured every minute using intravital video microscopy and a micrometer-calibrated video screen. Both BQ-123 and sarafotoxin S6c significantly reduced CFVs represented by the mean luminal stenosis (BQ-123=29+/-13% and sarafotoxin S6c=27+/-11% reduction, respectively; P<.05 for both, compared with saline). In contrast, BQ-788 significantly increased CFVs (33+/-6% increase, P<.05 compared with saline). Moreover, the inhibitory effect of sarafotoxin S6c on CFVs was completely abolished in the presence of N(omega)-nitro-L-arginine methyl ester (L-NAME) (a nitric oxide synthase inhibitor, 10(-5) mol/L) in superfusate over the arteries (16.1+/-5% increase, P=NS compared with saline in the presence of L-NAME). In addition, BQ-123 caused a significant increase in the diameter of the vessel distal to the injured segment (12+/-4% increase, P<.05 compared with saline). CONCLUSIONS: Endogenous ET-1 release from sites of vascular injury contributes to CFVs and vasomotor tone in the rat mesenteric artery CFV model. ETA and ETB receptors have differential roles in CFVs: ETA receptor antagonism and ETB receptor stimulation reduce CFVs, the latter at least partially through increased nitric oxide formation.

Animals↗
PubMed1997

Hypothalamic nitric oxide synthase is depressed in cholestatic rats.

We examined hypothalamic nitric oxide synthase (NOS) levels and release as well as steady-state mRNA levels in rats with cholestasis due to bile duct resection (BDR) and in sham-resected control rats. BDR rats had a significant reduction in hypothalamic NOS-containing neurons in the hypothalamic paraventricular nucleus as determined by NADPH-diaphorase staining, compared with sham-resected controls. In addition, NOS activity, measured indirectly by determining nitrite release from hypothalamic explants, was significantly lower in BDR rats compared with sham-resected animals. Hypothalamic steady-state NOS mRNA levels [brain constitutive NOS (bNOS)] were determined by semiquantitative reverse transcription-polymerase chain reaction and were found to be increased 1.5-fold in BDR rats compared with sham rats. In summary, BDR rats have diminished hypothalamic NOS levels and activity coupled with enhanced steady-state bNOS mRNA levels, suggesting that depressed hypothalamic NOS protein levels are due to posttranscriptional defects.

Animals↗
PubMed1997

Body distribution of free, liposomal and nanoparticle-associated mitoxantrone in B16-melanoma-bearing mice.

B16-melanoma-bearing mice were treated with four different formulations containing equivalent doses of the highly effective antineoplastic drug mitoxantrone. The formulations were: A mitoxantrone solution, a negatively charged liposome preparation (small unilamellar vesicles), a 14C-labeled polybutylcyanoacrylate- (PBCA) nanoparticle suspension, and a suspension of poloxamine 1508-coated 14C-PBCA-nanoparticles. After 1, 4 and 24 hr, three animals of each group were killed and the mitoxantrone concentrations in the blood, tumor, liver, spleen, heart and bone marrow were determined using an high performance liquid chromatography technique. Additionally, the concentrations of PBCA particles in the same tissues were measured by scintillation counting to compare the mitoxantrone distribution with the corresponding PBCA nanoparticle distribution. Each formulation led to a different body distribution profile of the drug. Liposomes drastically increased the blood level of mitoxantrone even after 24 hr, although free drug was cleared quickly. Liposomes also raised the concentration in the liver and spleen, but not the drug level in the tumor. PBCA-nanoparticles considerably increased the mitoxantrone concentrations in tumor, heart and spleen. However, the increase in tumor concentrations was not statistically significant due to the high variability. Nevertheless, the tumor growth was reduced significantly (P < .05) compared to both, the liposome and the solution preparation. The nanoparticle polymer concentrations did not completely mirror those of the drug concentrations. Especially in the heart, where no nanoparticle polymer radioactivity was found, the particle concentration did not completely correspond to the mitoxantrone concentration, revealing that a part of the drug was lost from the particles. These pharmacokinetic results correspond to parallel therapeutic effects obtained with mitoxantrone-loaded nanoparticles and liposomes in the B16 melanoma.

Animals↗
PubMed1996

Changing patterns of self-poisoning in a UK health district.

Details of admissions to a dedicated district poisons treatment unit in South Glamorgan were analysed to assess changes in self-poisoning patterns between 1987-1988 and 1992-1993. Self-poisoning rates increased in both men and women, with male rates showing a relatively larger increase, resulting in a fall in female to male ratio for person-based rates from 1.33:1 to 1.13:1. The highest age-specific rates in both period were found in 15-19-year-old females. Paracetamol was the most commonly ingested poison in 1992-1993, with 43.4% of episodes involving its use, compared with 31.3% of episodes in 1987-88. Antidepressant involvement in self-poisoning also increased from 11.3% of episodes in 1987-1988 to 17.6% of episodes in 1992-1993. Repetition of self-poisoning was relatively common, with 18% of admissions per year in 1992-1993 representing repeats. Although hospital admission increased in this health district over the study periods, this was not reflected in an increase in in-patient all-cause mortality, which was only 0.5% in 1987-1988 and 0.1% in 1992-1993.

Acetaminophen↗
PubMed1995

Exercises for chronic low back pain: a clinical trial.

Different training models are effective for the treatment of chronic low back pain, but no consensus has been found. Earlier studies have emphasized training of spinal mobility and back strength. To evaluate if other physiological parameters, such as coordination, are of equal importance, we performed a randomized trial on 40 consecutive patients with chronic low back pain. Two training models were compared: 1) intensive training of muscle endurance and 2) muscle training, including coordination. In both groups, training was performed 1 hour twice a week for 3 months. Pain score, disability score, and spinal mobility improved in both training groups without differences between the two groups. Only intensive training of muscle endurance improved isokinetic back muscle strength. At study entry, we found a significant correlation between spinal mobility and dysfunction, but after the training, no correlation was found between improvement of spinal mobility or isokinetic back extension strength and improvement of function or pain level. We conclude that coordination training for patients with chronic low back pain is as equally effective as endurance training.

Adolescent↗