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Biomedical subjects

H Fischer

Publications and source records attributed to H Fischer.

At least 199 records · Page 11Linked to original sources

Affective and attentive neural networks in humans: a PET study of Pavlovian conditioning.

Using positron emission tomography (PET) and [15O]butanol we studied regional cerebral blood flow (rCBF) to a visual snake stimulus before and after classical conditioning with an unconditioned electric shock delivered to the right hand. Measures of heart rate, electrodermal activity, state anxiety and subjective distress confirmed classical conditioning of physiological and subjective responses. Subcortically, conditioning increased rCBF bilaterally in the ventromedial thalamus, the posterior hypothalamus and the central grey of the midbrain. Cortically, rCBF increased in the left anterior and posterior cingulate gyrus, the left primary somatosensory cortex, the left premotor cortex and bilaterally in parietal areas. Thus, the functional organization of classical conditioning in humans involves autonomic, affective and attentive brain mechanisms.

Adult↗

The actin filament disrupter cytochalasin D activates the recombinant cystic fibrosis transmembrane conductance regulator Cl- channel in mouse 3T3 fibroblasts.

1. Cytochalasin D (CD; 5 microM) readily stimulated cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel activity in cell-attached and whole-cell patch recordings from 3T3 fibroblasts expressing recombinant CFTR but not in mock-transfected cells. CD-stimulated currents were indistinguishable from those evoked by forskolin stimulation. Kinetic analysis of CFTR gating showed identical channel behaviour independent of the agonist used. 2. To elucidate the mechanism of action of CD we tested its effects on cAMP, protein kinase A, and the CFTR itself during CD stimulation. In contrast to forskolin treatment, CD did not increase cellular cAMP content. 3. A direct interaction of CD with the CFTR was ruled out because CD showed no effect on CFTR in excised inside-out patches. 4. CD effects were fully blocked when the cellular protein kinase A was inhibited by treatment of cells with RpcAMPS in cell-attached patches or when protein kinase inhibitor peptide was dialysed into cells in whole-cell experiments. 5. Addition of G-actin to excised patches had no effects on CFTR. 6. We conclude that the stimulatory effect of CD is cAMP independent, but needs a functional protein kinase A in order to activate the CFTR. We propose that cytochalasin D activates CFTR by releasing a cellular inhibitor, e.g. a phosphatase, that is held in place by F-actin.

Actins↗

CD8-depleted donor lymphocyte infusion as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation.

Donor lymphocyte infusions can reinduce complete remission in the majority of patients with chronic myelogenous leukemia (CML) who relapse into chronic phase after allogeneic bone marrow transplantation (BMT). Such infusions are associated with a high incidence of graft-versus-host disease (GVHD) and marrow aplasia. BMT using selective depletion of CD8+ lymphocytes from donor cells reduces the incidence of GVHD without an increase in leukemia relapse. We hypothesized that infusion of CD8-depleted donor peripheral blood lymphocytes could also reinduce complete remissions with a lesser potential to produce symptomatic GVHD in patients with CML who relapsed after allogeneic BMT. Ten patients with Ph(+) CML who relapsed a median of 353 days after BMT (range, 82 to 1,096 days) received donor lymphocyte infusions depleted of CD8+ cells. Nine patients received a single infusion and 1 received two infusions. Four patients were treated while in chronic phase with clonal evolution, 2 during accelerated phase, 3 during blast crisis, and 1 in a cytogenetic relapse. A mean of 0.9 +/- 0.3 x 10(8) mononuclear cells/kg were infused, containing 0.6 +/- 0.4 x 10(6) CD3+CD8+ cells/kg. Six patients achieved hematologic and cytogenetic remission at 4, 8, 11, 15, 39, and 54 weeks after lymphocyte infusion. Two patients developed > or = grade II acute GVHD, and 1 patient developed mild chronic GVHD. We conclude that donor lymphocyte infusions depleted of CD8+ cells can induce remissions with a low rate of severe acute GVHD in patients with CML who relapse after allogeneic BMT, supporting the hypothesis that CD8+ lymphocytes are important effectors of GVHD, but may not be essential for the graft-versus-leukemia effect against this disease. Further controlled studies are required to confirm these preliminary observations.

Acute Disease↗

[Primary systemic amyloidosis with cardiac manifestations].

HISTORY AND FINDINGS: A Vietnamese woman, now 68 years old, had for ten years been known to have a monoclonal lambda light-chain gammopathy. Two years before the present admission her resting ECG had shown absent R waves in V2 to V4, first-degree A-V block and preterminal negative T waves. Results of left heart catheterization and echocardiography were essentially normal. Gradually increasing dyspnoea over the preceding 9 months, recently even at rest, and a poor general state with clinical signs of heart failure led to her hospital admission. TESTS: Laboratory tests confirmed the known gammopathy without evidence of plasmacytoma. An echocardiogram now demonstrated a moderately enlarged left atrium and hypertrophied left ventricular wall, as well as restrictive function with an increased ratio of early to late diastolic filling velocity and shortened deceleration time. Myocardial echogenicity was increased. Rectal biopsy showed numerous interstitial and paravascular amyloid fibrillae. All these findings indicated restrictive cardiomyopathy as part of primary systemic amyloidosis. TREATMENT AND COURSE: After treatment with frusemide (80 mg twice daily) and pacemaker implantation she was discharged, her cardiac status now in NYHA class III. Neither chemotherapy nor cardiac transplantation is contemplated.

Aged↗

Characterization and evolutionary relationships of Magnolia legumin-encoding cDNAs representing two divergent gene subfamilies.

We have cloned and sequenced three different cDNAs encoding legumins of Magnolia salicifolia. Analysis of the nucleotide and derived amino acid sequences shows that the cDNAs designated A2, A11, and B14 represent two divergent subfamilies with nucleotide similarities of only about 55%. The B14 cDNA codes for a relatively methionine-rich legumin precursor, and the beta-chain of this protein is shown to be glycosylated; neither feature is common in legumin. In an evolutionary analysis, the B14 legumin cDNA is relatively similar to gymnospermous legumin sequences and paralogous to all angiosperm legumins hitherto known. The A legumin sequence clusters with those of monocot legumins in a low angiosperm branch. We conclude that the evolution of legumin genes in angiosperms involved an early gene duplication which resulted in the progenitor of the B14 legumin, on the one hand, and the progenitor of A2, A11 and modern angiosperm legumins, on the other hand.

Amino Acid Sequence↗

Bioelectrical impedance analysis as a predictor of survival in patients with human immunodeficiency virus infection.

In patients with AIDS, short-term survival has been related to body weight, body composition, and serum nutritional parameters, but their prognostic impact at earlier stages of the HIV infection is not known. With an individual follow-up period of 1,000 days, we investigated the prognostic relevance of electrical tissue conductivity [resistance R, reactance Xc, phase angle alpha, extracellular mass (ECM), body cell mass (BCM)] measured by bioelectrical impedance analysis, of the CD4+ cell count, and of serum parameters indicating malnutrition in 75 HIV-infected male patients at Walter Reed stages 3-5. After initial recording, 29 patients (38.7%) died from AIDS during this period. Among 12 parameters estimated with a semiparametric Cox regression model adjusted for therapy (pentamidine, azidothymidine), the phase angle alpha (parameter estimate: -1.043, 95% confidence interval of -0.61 to -1.47; p < or = 0.0001), the ECM/BCM ratio, Xc, BCM, serum cholesterol, number of CD4+ cells, and serum albumin had significant prognostic influence on survival, whereas age, body weight, body mass index, resistance, serum protein, and serum triglycerides did not. In a model with four covariates (CD4+ cells, phase angle, pentamidine, azidothymidine), the prognostic impact of the CD4+ cell count (parameter estimate: -0.549) was lower compared with the phase angle alpha (parameter estimate: -0.799; p < or = 0.0001) and did not gain statistical significance (p = 0.0626). The phase angle alpha was the best single predictive factor for survival among all 12 parameters (comparison of the respective Cox models with the likelihood ratio test).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Adenosine release in the ventral striatum of the rat is modulated by endogenous nitric oxide.

The influence of nitric oxide (NO) on adenosine release was investigated by the push-pull technique in the ventral striatum of the urethane-anaesthetized rat. Superfusion with the NO donor diethylamine-NO enhanced, whereas superfusion with the NO synthase inhibitor L-NG-nitroarginine methyl ester decreased the output of adenosine. The effect of L-NG-nitroarginine methyl ester was abolished by L-arginine methyl ester. These findings indicate that, in the ventral striatum of the rat, NO modulates adenosine release.

Adenosine↗

Nitric oxide modulates the release of acetylcholine in the ventral striatum of the freely moving rat.

The influence of nitric oxide on acetylcholine release in the ventral striatum was investigated by the push-pull superfusion technique in the conscious, freely moving rat. Superfusion with the nitric oxide donors S-nitroso-N-acetylpenicillamine or with 3-morpholino-sydnonimine caused a pronounced increase in striatal acetylcholine release. This effect was prevented by superfusion with tetrodotoxin. Pre-superfusion with the guanylyl cyclase inhibitor methylene blue abolished the effect of 3-morpholino-sydnonimine. Superfusion of the ventral striatum with the guanylyl cyclase inhibitor LY83583 decreased acetylcholine release by 60% of basal release, whereas the less specific guanylyl cyclase inhibitor methylene blue was ineffective in this respect. Superfusion of the ventral striatum with inhibitors of nitric oxide synthase also led to different effects on basal acetylcholine release. Superfusion with L-NG-methylarginine did not influence basal acetylcholine release, whereas superfusion with L-NG-nitroarginine or with L-NG-nitroarginine methyl ester led to a substantial decrease in acetylcholine output, the latter compound being more effective. The effect of L-NG-nitroarginine was abolished by simultaneous superfusion with L-arginine. The effects of NO donors and of LY83583 suggest that NO increases acetylcholine release, probably by a cGMP-dependent mechanism. The effectiveness of nitric oxide synthase inhibitors shows that the activity of striatal neurons is under the permanent influence of nitric oxide, that leads, via a direct or indirect mechanism, to continuous enhancement of acetylcholine release. In conclusion, our findings suggest that NO synthesized in the ventral striatum acts as an intracellular messenger which modulates acetylcholine release.

Acetylcholine↗

Plasma amino acid consumption and pancreatic secretion during and after cerulein-induced pancreatitis in rats.

The decrease in pancreatic exocrine secretion during the course of acute pancreatitis is a well-documented process. However, the mechanisms underlying this reduced pancreatic function are not fully understood. To analyze pancreatic protein synthesis and secretion during and after cerulein-induced pancreatitis, we performed the plasma amino acid consumption test on conscious rats. After stimulation with 1 microgram cerulein/kg/h sc for 1 h, the control group with intact pancreas exhibited a decrease in plasma amino acid by about 15%, and this decrease could be abolished by the administration of the specific CCK-receptor antagonist, loxiglumide. Protein and amylase secretion were augmented by cerulein to about 400% of control values. Upon supramaximal stimulation of the pancreas with cerulein (20 micrograms/kg/h sc for 5 h), we observed a profound decrease of pancreatic secretion, which was accompanied by a more prolonged and more pronounced decrease of plasma amino acids (25%). Two hours after cessation of the supramaximal stimulation of pancreatic secretion (to induce pancreatitis), the administration of 1 microgram/kg/h of cerulein for 1 h resulted in a further decrease of amino plasma acid level, whereas no stimulation of exocrine pancreatic secretion was observed. Eighteen hours later, repeated administration of 1 microgram/kg/h of cerulein was still able to induce amino acid decrease by 20%, but again, no stimulation of exocrine pancreatic secretion was detectable. We conclude that, in the time course of acute cerulein-induced hyperstimulation, there might be an imbalance between synthesis of pancreatic enzymes (reflected by amino acid consumption) and the release of exocrine pancreatic secretion into the duodenum, which may be explained by leakage of proteolytic enzymes from damaged acinar cells into the extracellular space of the pancreas.

Amino Acids↗

Depth profiling by ARXPS in surface analysis.

A method of nondestructive depth profiling in near surface regions of solids is described. Models have been discussed from which algorithms for evaluation of measured data are obtained. The algorithms, based on standard profiles with free parameters, have been adjusted to the data resulting from angle resolved XPS (ARXPS) by means of least squares fits. Depth profile analyses and segregation studies were performed on Pt-Ni and Fe-S specimens.

Journal Article↗

Type I skin reactivity to native and recombinant phospholipase A2 from honeybee venom is similar.

Phospholipase A2 is the major allergen in honeybee venom. Recombinant phospholipase A2 was produced in prokaryotes and tested for its biologic activity by intracutaneous skin testing with serial 10-fold dilutions in comparison with native and deglycosylated phospholipase A2 in patients allergic to bee venom. Linear regressions of the log of the wheal area versus the log of the allergen concentration were calculated for all allergens in each patient. The relative allergenic potency of the various preparations was analyzed by comparing the linear regressions. Native phospholipase A2 was about 10 times more potent than whole bee venom. None of 58 patients allergic to bee venom was missed by testing with native phospholipase A2 alone. This allergen and deglycosylated native phospholipase A2 resulted in similar skin reactions, indicating that the sugar residues were of little relevance for IgE-binding in the patients tested. Native phospholipase A2 also had relative potency similar to that of recombinant refolded phospholipase A2, whereas recombinant nonrefolded phospholipase A2 had almost no biologic activity in skin testing. These results demonstrate in vivo activity of the recombinant bee venom allergen phospholipase A2. Although correct refolding is a prerequisite for type I skin reactivity, glycosylation seems to be less important.

Adult↗

[Radiation exposure of radiologists during angiography: dose measurements outside the lead apron].

The aim of this study was to provide practical information to angiographers concerning radiation exposure to body parts not covered by lead aprons. Individual doses to the neck and hands of radiologists measured in micro-Sieverts were obtained during the course of 80 angiographies of various types. The number of diagnostic and interventional procedures, which might lead to exceeding permissible doses, have been calculated. Possibilities of estimating doses during angiography by means of parameters such as screening times were examined statistically. Especially with regard to the hands, estimations of the doses are insufficient (correlation r = 0.21). Radiologists who undertake much angiographic and particularly interventional work may reach exposure levels requiring protective measures in addition to lead aprons.

Angiography↗