[Clinical and histopathological examinations in the allergic rhinitis].
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Biomedical subjects
Publications and source records attributed to J Schmidt.
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AIM: To examine efficacy and tolerability of a single daily dose of 6 mg quadropril (spirapril). MATERIAL AND METHODS: An open multicenter study enrolled 5000 out-door patients with hypertension. All the patients received an ACE inhibitor quadropril for 3 months with four control visits (on week 0, 4, 8 and 12). RESULTS: Quadropril caused a marked decrease in systolic and diastolic blood pressure. At the end of the study 89.4% of patients had a systolic blood pressure reduction of at least 15 mm Hg and 85.4% had a diastolic blood pressure reduction of at least 10 mm Hg. There were no clinically significant heart rate changes. The overall tolerability of the drug was estimated as good or very good in 95.3% of patients. Only 2.9% of patients had side effects during treatment with once daily dose of 6 mg quadropril. No serious side effects were observed. CONCLUSION: 6 mg daily dose of quadropril is an effective and safe therapy for arterial hypertension.
The authors pursue longitudinal studies since 1972 on a defined population of 106,000 relating to several questions of the aortic dissection. Till now, in 90 patients 93 cases of the aortic dissection were found. In seven patients, the aortic dissection was complicated with the clinical and pathological symptoms of surgical diseases. The vascular complications of the aortic dissection caused obstruction of coecomesenteric arteries with severe ischemic signs in four patients, obstruction of iliac arteries in two patients and the left sublavian artery in one another. In an additional patient with a chronic recurrent pancreatitis, the acute aortic dissection as an acute exacerbation of chronic pancreatitis was considered. It makes known in a short report of cases the clinicopathological features of vascular complications of the thoracoabdominal aortic dissections. Their pathomechanisms as well as the possibilities of their diagnosis and treatment are reviewing in detail.
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Heme oxygenase-1 (HO-1) is an inducible enzyme involved in heme catabolism, tissue iron homeostasis and the cellular response to oxidative stress. Elevated HO-1 expression in astrocytes has been observed in association with abnormal iron deposition and increased oxidative stress in Parkinson's disease (PD). Since HO-1 could contribute to these aspects of PD pathobiology we have investigated its regulation in cultured astrocytes and C6 glioma cells. Here we report that dopamine is a potent inducer of HO-1. This induction is not mediated by a classical dopamine receptor and is not mimicked by a range of catecholamines and dopamine metabolites. When the time-course of HO-1 expression was compared between dopamine and hemin, the latter induced the gene immediately while the former did so with a lag. This suggested two distinct signal transduction pathways. However, cycloheximide blocked both hemin- and dopamine-induced HO-1 expression, suggesting that both pathways may involve proteins with short half-lives. Ascorbic acid blocked dopamine induction of HO-1 but had no effect on hemin-induced expression. This suggested that dopamine may signal upstream of the unstable protein by producing pro-oxidant metabolites or byproducts. Inhibition of monoamine oxidases A or B or catechol-O-methyl transferase did not block HO-1 induction by dopamine, indicating that these enzymes were not converting dopamine to an active metabolite. These results suggest that dopamine, released or secreted from affected neurons, may trigger HO-1 expression in neighboring astrocytes. HO-1 and its metabolites could then contribute to the oxidative stress and iron deposition associated with PD.
Vinblastine and vincristine are two medically important bisindole alkaloids from Catharanthus roseus (Madagascar periwinkle). Attempts at production in cell cultures failed because a part of the complex pathway was not active, i.e. from tabersonine to vindoline. It starts with tabersonine 16-hydroxylase (T16H), a cytochrome P450-dependent enzyme. We now show that T16H is induced in the suspension culture by light and we report the cloning of the cDNA. The enzyme was expressed in Escherichia coli as translational fusion with the P450 reductase from C. roseus, and the reaction product was identified by mass spectrometry. The protein (CYP71D12) shares 47-52% identity with other members of the CYP71D subfamily with unknown function. The induction by light was strongly enhanced by a nutritional downshift (transfer into 8% aqueous sucrose). We discuss the possibility that the entire pathway to bisindoles can be expressed in suspension cultures.
Cri-du-chat syndrome is due to a partial deletion of the short arm of chromosome 5 and comprises a catlike cry, minor facial anomalies, growth delays, and psychomotor retardation. We identified a family with an insertion involving chromosome areas 5p and 16q. Four relatives are balanced carriers and have a normal phenotype, 5 have inherited the insertion in an unbalanced form with 2 resulting in partial trisomy of 5p and 3 in partial monosomy of 5p. The 3 individuals show a variable phenotype with respect to mental delay and some of the findings of cri-du-chat syndrome. The extent of the 5p deletion in this family was determined using previously mapped markers. The deletion in this family was informative for further refining the phenotypic map for the cri-du-chat syndrome. This family demonstrates the importance of performing phenotype-genotype correlation studies based on the presence rather than the absence of abnormalities.
Low-temperature single-molecule spectroscopic techniques were applied to a light-harvesting pigment-protein complex (LH2) from purple photosynthetic bacteria. The properties of the electronically excited states of the two circular assemblies (B800 and B850) of bacteriochlorophyll a (BChl a) pigment molecules in the individual complexes were revealed, without ensemble averaging. The results show that the excited states of the B800 ring of pigments are mainly localized on individual BChl a molecules. In contrast, the absorption of a photon by the B850 ring can be consistently described in terms of an excitation that is completely delocalized over the ring. This property may contribute to the high efficiency of energy transfer in these photosynthetic complexes.
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Achilles tendon ruptures are among of the most frequent tendon ruptures. Usually middle aged men with infrequent sports activity are involved. In most cases histopathology reveals degenerative changes within the tendon. Unusual rupture location and physical signs of trauma should lead one to consider a traumatic origin of the rupture. Traumatic origin can be confirmed by the accident history and physical signs as well as with the histopathology of the rupture site and possibly a tissue section far away the rupture site. This information can be helpful in insurance inquiries.
The renin-angiotensin system may contribute to the pathogenesis of atherosclerosis. A common feature of all stages of atherosclerosis is inflammation of the vessel wall. The transcription factor nuclear factor-kappaB (NF-kappaB) participates in most signaling pathways involved in inflammation. This study therefore examined the effect of angiotensin (ANG) II on NF-kappaB activation in monocytic cells, a major cellular component of human atheroma, by electrophoretic mobility shift assay. ANG II, like TNFalpha, caused rapid activation of NF-kappaB in human mononuclear cells isolated from peripheral blood by Ficoll density gradient. This ANG II effect was blocked by the angiotensin AT1 receptor antagonist losartan. Specificity of ANG II-induced NF-kappaB activation was ascertained by supershift and competition experiments. Moreover, ANG II stimulated NF-kappaB activation in human monocytes, but not in lymphocytes from the same preparation. Together, the data demonstrate the ability of the vasoactive peptide ANG II to activate inflammatory pathways in human monocytes.
A series of new N-(pyridin-4-yl)-(indol-3-yl)alkylamides 44-84 has been prepared in the search of novel antiallergic compounds. Synthesis of the desired ethyl (2-methyindol-3-yl)acetates 1-4 was achieved by indolization under Fischer conditions; Japp-Klingemann method followed by 2-decarboxylation afforded the ethyl (indol-3-yl)alkanoates 17-25. Amidification was successfully carried out by condensation of the corresponding acids or their N-aryl(methyl) derivatives with 4-aminopyridine promoted by 2-chloro-1-methylpyridinium iodide. Efforts to improve the antiallergic potency of the title series by variation of the indole substituents (R1, R2, R) and the length of the alkanoic chain (n = 1, 2, 3) led to the selection of N-(pyridin-4-yl)-[1-(4-fluorobenzyl)indol-3-yl]acetamide 45, out of 41 compounds. This amide was 406-fold more potent than astemizole in the ovalbumin-induced histamine release assay, using guinea pig peritoneal mast cells, with an IC50 = 0.016 microM. Its inhibitory activity in IL-4 production test from Th-2 cells was identical to that of the reference histamine antagonist (IC50 = 8.0 microM) and twice higher in IL-5 assay: IC50 = 1.5 and 3.3 microM, respectively. In vivo antiallergic activity evaluation confirmed efficiency of 45 in sensitized guinea pig late phase eosinophilia inhibition, after parenteral and oral administration at 5 and 30 mg/kg, respectively. Its efficiency in inhibition of microvascular permeability was assessed in two rhinitis models; ovalbumin and capsaicin-induced rhinorrhea could be prevented after topical application of submicromolar concentrations of 45 (IC50 = 0.25 and 0.30 microM); and it also exerted significant inhibitory effect in the first test after iv and oral administration, with ID50 = 0.005 and 0.46 mg/kg.
Hydroxycinnamoyl-CoA:tyramine N-(hydroxycinnamoyl)transferase (THT; EC 2.3.1.110) catalyzes the transfer of hydroxycinnamic acids from the respective CoA esters to tyramine and other amines in the formation of N-(hydroxycinnamoyl)amines. Expression of THT is induced by Phytophthora infestans, the causative agent of late blight disease in potato. The amino acid sequences of nine endopeptidase LysC-liberated peptides from purified potato THT were determined. Using degenerate primers, a THT-specific fragment was obtained by reverse transcription-polymerase chain reaction, and THT cDNA clones were isolated from a library constructed from RNA of elicitor-treated potato cells. The open reading frame encoding a protein of 248 amino acids was expressed in Escherichia coli. Recombinant THT exhibited a broad substrate specificity, similar to that of native potato THT, accepting cinnamoyl-, 4-coumaroyl-, caffeoyl-, feruloyl- and sinapoyl-CoA as acyl donors and tyramine, octopamine, and noradrenalin as acceptors tested. Elicitor-induced THT transcript accumulation in cultured potato cells peaked 5 h after initiation of treatment, whereas enzyme activity was highest from 5 to 30 h after elicitation. In soil-grown potato plants, THT mRNA was most abundant in roots. Genomic Southern analyses indicate that, in potato, THT is encoded by a multigene family.
Hyperpolarizing responses in neuropil glial cells evoked by nerve root stimulation were studied in the central nervous system of the leech Hirudo medicinalis using intracellular recording and extracellular stimulation techniques. From a mean resting potential of -60.5 +/- 1.0, the glial membrane was hyperpolarized by -8.6 +/- 0.8 mV, via stimulation of the dorsal posterior nerve root in an isolated ganglion. Nerve root stimulation evoked biphasic or depolarizing responses in glial cells with resting potentials around -70 mV (Rose CR, Deitmer JW. J. Neurophysiol. 73:125-131, 1995). The hyperpolarizing response was reduced by the ionotropic glutamate receptor antagonist CNQX (50 microM) to 58% of its initial amplitude. In 15 mM Ca2+/15 mM Mg(2+)-saline the hyperpolarization was reduced by 44%. The hyperpolarization that persisted in high-divalent cation saline was not affected by CNQX. Bath-applied glutamate (500 microM) and kainate (2 microM) elicited glial hyperpolarizations that were sensitive to CNQX and 10 mM Mg2+/1 mM Ca(2+)-saline. The 5-HT-antagonist methysergide did not affect the hyperpolarizations evoked by nerve root stimulation. The results show that in the leech glial membrane responses to neuronal activity include not only depolarizations, as shown previously, but also hyperpolarizations, which are mediated by direct and indirect neuron-glial communication pathways. In the indirect pathway, glutamate is a transmitter between neurons.
This presentation describes a research project investigating the suitability of model-based Workflow Management Systems (WfMS) to support radiological process. The following aspects are covered: process modeling, process enactment, and architecture of workflow-enabled application systems.
BACKGROUND: The purpose of this study was to compare the regression of the tumor-distant exudative detachment that accompanies malignant melanoma with regression of the tumor as a result of ruthenium-106 irradiation. METHODS: From 1994 until the beginning of 1996 we treated 28 patients with choroidal malignant melanoma with radioactive plaque therapy. Follow-up examinations were completed 3 and 6 weeks, 3, 6 and 12 months after therapy and finally at 1 year or half-year intervals. Twenty-three patients met the study requirements. RESULTS: Initially, after irradiation there was an increase in the retinal detachment. In 15 patients (65%) we found rapid regression of the detachment, accompanied by distinct tumor regression (61%). One of these patients revealed only minor tumor regression in spite of regression of the exudative detachment. Three months after radiation, 8 patients showed no rapid regression of the exudative detachment. Two of these patients had to undergo a second irradiation and 2 were enucleated because of absent tumor regression. One patient died. Three patients showed an increase in the detachment, accompanied by tumor regression. CONCLUSIONS: Rapid regression of the exudative detachment (> or = 50% of the preoperative detachment) approximately 3 months after irradiation seems to be of good prognostic value for tumor regression.
The motor program for heartbeat in the medicinal leech is produced by a central pattern generator that regularly switches between two alternative coordination states. A pair of switch heart interneurons reciprocally alternate between rhythmically active and inactive states to effect these switches. During spontaneous switches in the activity state of switch interneurons, there was no correlation between the duration of a particular activity state and beat period, indicating that the timing networks for the switch cycle and the beat cycle are relatively independent. Simultaneous recordings from two switch heart interneurons showed that a perturbation in the electrical activity of one does not influence switching of the other and that there is no synaptic interaction between them. Using voltage clamp, we characterized an L-like Ca2+ current (measured as Ba2+ currents), inactivating and non-inactivating K+ currents, a persistent Na+ current, and a hyperpolarization-activated inward current in switch interneurons. Dynamic clamp experiments show that "subtraction" of an artificial switch leak conductance (described previously by Gramoll et al. 1994) from a switch interneuron when it is in the inactive state causes it to display activity associated with the active state. We discuss how the switch leak conductance may interact with the intrinsic currents of switch interneurons to control their activity state.