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Biomedical subjects

C Schmidt

Publications and source records attributed to C Schmidt.

At least 289 records · Page 16Linked to original sources
PubMed1995

Nuclear and nucleolar targeting of human ribosomal protein S6.

Chimeric proteins were constructed to define the nuclear localization signals (NLSs) of human ribosomal protein S6. The complete cDNA sequence, different cDNA fragments and oligonucleotides of the human ribosomal proteins S6, respectively, were joined to the 5' end of the entire LacZ gene of Escherichia coli by using recombinant techniques. The hybrid genes were transfected into L cells, transiently expressed, and the intracellular location of the fusion proteins was determined by their beta-galactosidase activity. Three NLSs were identified in the C-terminal half of the S6 protein. Deletion mutagenesis demonstrated that a single NLS is sufficient for targeting the corresponding S6-beta-galactosidase chimera into the nucleus. Removal of all three putative NLSs completely blocked the nuclear import of the resulting S6-beta-galactosidase fusion protein, which instead became evenly distributed in the cytoplasm. Chimeras containing deletion mutants of S6 with at least one single NLS or unmodified S6 accumulated in the nucleolus. Analysis of several constructs reveals the existence of a specific domain that is essential but not sufficient for nucleolar accumulation of S6.

Amino Acid Sequence↗
PubMed1995

An implantable seal-less centrifugal pump with integrated double-disk motor.

Thrombus formation and sealing problems at the shaft as well as the compact and efficient design of the driving unit have been major difficulties in the construction of a long-term implantable centrifugal pump. To eliminate the problems of the seal, motor size, and efficiency, two major steps were taken by modifying the Vienna implantable centrifugal pump. First, a special driving unit was developed, in which the permanent magnets of the motor themselves are used for coupling the force into the rotor. Second, the rotor shaft in the pumping chamber was eliminated by adopting a concept recently presented by Ohara. The rotor is supported by 3 pins, which run on a carbon disk, whose concave shape leads to stabilization. The device has the following specifications: size: 65 mm (diameter) by 35 mm (height), 101 cm3; priming volume 30 cm3, 240 g; and a 6-pole brushless double disk DC motor. The required input power of the described prototype is 15 W at 150 mm Hg, 5 L/min (overall eta = 11%), and has an in vitro index of hemolysis (IH) of 0.0046 g/100 L. The test for in vitro thrombus growth exhibited far less thrombus formation in the new design than in designs with axles. In conclusion, the design of a special driving unit and the elimination of the axle led to the construction of a small pump with very low blood traumatization.

Biomechanical Phenomena↗
PubMed1995

A clinical monitoring system for centrifugal blood pumps.

In clinical application of rotary blood pumps, flow obstruction as a result of suction of the inflow cannula, kinking of tubing, or thrombus formation occurs quite frequently. Early detection of such problems is essential to avoid hemolysis, tissue degradation, or release of thrombi to the patient. A program was developed for automatic observation of pump performance, tubing resistance, and suction effects, which requires only the measurement of already available parameters (i.e., pump speed, pump flow, aortic pressure). The software is based on Visual-C and provides a user surface formatted in Windows. Pump flow, its time derivate, and the relationship between the pulsatile component and the mean graft flow are observed to detect suction in the left atrium. Furthermore, the generated pressure head is predicted from pump speed, graft flow, and the resistance of tubing/cannula and compared with the actually measured aortic pressure. An alarm sounds if a given limit between prediction and measurement is exceeded. In a mock circulation, suction events were detected in more than 95% with a mean deviation of actual aortic pressure from its predicted value of less than 5%. For in vivo application, even incomplete suction could be detected reliably in more than 90% of events. This system improves and standardizes monitoring of pump performance; it should therefore lead to greater safety during application of such devices.

Algorithms↗
PubMed1995

An artificial neural network-based noninvasive detector for suction and left atrium pressure in the control of rotary blood pumps: an in vitro study.

Rotary blood pumps are used in clinical applications to assist circulation via pumping blood from the left atrium to the aorta. Negative inflow pressures at high flow rates can cause suction of the cannula in the left atrium with deleterious effects on the atrial wall, the blood, and the lung. Therefore, stable and reliable detection of suction and the prediction of the left atrium pressure (LAP) would be of major interest for the control of these pumps. This work reports about an in vitro study of such a detector based on artificial neural networks (ANN). In the first project phase, an ANN was used to estimate the LAP based on pump speed, pump flow, and aortic pressure, obtained from a mock circulation. The inputs for the ANN were 11 characteristic values computed from these three parameters. In the second phase, another ANN was trained to classify various system states, such as suction, danger of suction (a state close to actual suction), and no suction. The first ANN was able to estimate the LAP with an accuracy of +/- 1.8 mm Hg. The discrimination of suction versus the other two states could be performed with a sensitivity and specificity of about 95% while the more interesting task of distinguishing danger of suction from no suction reached a sensitivity and specificity of about 65% (leaving 25% of each class unclassified and 10% of each class incorrectly classified).(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Function↗
PubMed1995

Treatment of active Crohn's ileocolitis with oral pH-modified budesonide. Germany Budesonide Study Group.

Budesonide is a topical steroid which after intestinal absorption is rapidly degraded into inactive metabolites in the liver. Its systemic bioavailability is only 10-15%. In the present open trial the efficiency and safety of oral pH-modified release budesonide were assessed in patients with active Crohn's ileocolitis. This report describes the results of the first 30 of 78 patients. After 6 weeks of treatment with 3 x 3 mg budesonide/day 67% of the patients were in clinical remission. Typical steroid-related side effects were observed in only one patient. Budesonide therefore seems to be suited as an alternative for classical steroids in patients with Crohn's ileocolitis. Its clinical efficacy is comparable with classical steroids but it's rate of steroid-related side effects is lower.

Administration, Oral↗
PubMed1995

Induction of flare-up reactions in rat antigen-induced arthritis.

Flare-up reactions were induced in the rat chronic antigen-induced arthritis model (AIA), similar to those in mice and rabbits. After two consecutive immunizations (500 micrograms each, Day -21 and -14) with methylated bovine serum albumin (mBSA) in complete Freund's adjuvant (CFA), a biphasic primary arthritis was induced on Day 0 by intra-articular (i.a.) injection of 100 micrograms mBSA. The acute arthritic phase lasted 1 week, followed by chronic, mild joint swelling. Flare-up could then be induced on Day 40 by a second i.a. injection of 10-100 micrograms mBSA into the knee, with maximal flare-up reaction 2 days following the i.a. injection, and a return to chronic levels within 2 weeks. On Day 6 after induction of the flare-up, the inflamed joint showed massive cartilage and bone destruction; high numbers of alpha beta-T-cell-receptor-positive cells and macrophages, but only a few IL-2-receptor-carrying cells were detected in the inflamed synovial membrane. Induction of a second flare-up, 40 days after the first one, was possible by i.a. injection of 100 micrograms mBSA. Unlike in the mouse model, intravenous injection of up to 10 mg mBSA failed to induce flare-ups in the chronically inflamed joint.

Animals↗
PubMed1995

[Ocular vasospasm in cold provocation test and primary vascular acrosyndrome].

An ocular vasospasm induced by cold has been searched among 8 patients carrying primary vasospastic disease without any ocular pathology. Ocular vasospasm which is characterized by visual field defect was searched with Statpac 24-2 test using HUMPHREY autoperimeter. A baseline visual field was performed first, then a second after provocation by dipping the hand in cold water (13 degrees) and a third after oral administration of 10 mg of Nifedipine. Two patients had ocular vasospasm that regressed after Nifedipine administration. These two patients might have a higher risk to develop normal tension glaucoma.

Adult↗
PubMed1995

[Surgical therapy of acute tricuspid valve endocarditis: indications, technique and results].

Tricuspid valve endocarditis is treated by antibiotics alone in the majority of the cases. However, intractable infection or hemodynamic compromise may warrant surgery. In those cases total valve-excision or valve-replacement had been the most common surgical procedures. Both are controversial in regards to the hemodynamic consequences and to the long-term prognosis. In the following, results of tricuspid valve repair in acute infective endocarditis are reported and discussed as an additional treatment option. Between January 1988 and December 1993, 118 patients were operated for acute valve endocarditis at our institution. Eleven of these patients had tricuspid valve endocarditis, isolated (n = 7) or combined with endocarditis of a left-sided valve (n = 4). In the cases with isolated tricuspid valve endocarditis, the indication for surgery was intractable infection in 6 and hemodynamically relevant tricuspid-insufficiency in 1 out of 7 patients, respectively. In all patients with associated left-sided endocarditis, the indication was hemodynamic deterioration. In 8 patients the tricuspid valve endocarditis was treated as follows: Debridement, vegectomy, patch-reconstruction of the cusps, bicuspidalization. In 3 patients reconstruction was not possible because of extended involvement of all parts of the valve, including the valve ring and the papillary muscles. In these patients, primary valve-replacement (n = 1) or valve-excision with secondary replacement (n = 2) was performed. In 4 patients tricuspid-reconstruction was combined with mitral- (n = 1), aortic- (n = 1) or double-valve replacement (n = 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Arachidonic acid metabolism and intracellular calcium concentration in inflammatory bowel disease.

OBJECTIVE: To study the alteration of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) synthesis and intracellular Ca2+ concentration in chronic inflammatory bowel disease, and to ascertain the effect of anti-inflammatory drugs and other mediators on eicosanoid synthesis and Ca2+ concentration. METHODS: Biopsies taken from the descending colon were isolated biochemically. The suspension of isolated mucosal cells was incubated for 15 min in the presence and absence of arachidonic acid and the Ca2+ ionophore A23187. PGE2 and LTB4 concentrations in the incubation medium were measured by radioimmunoassay, and the intracellular Ca2+ concentration was determined using fura-2. We studied 107 subjects. In addition, the effects of bradykinin, endothelin, cyclosporin A and PGE2 on intracellular Ca2+ concentration were determined in 25 individuals. RESULTS: Untreated patients with active inflammatory bowel disease showed a significant increase in LTB4 synthesis compared with healthy controls. However, in patients receiving steroids, sulphasalazine or 5-aminosalicylic acid, both LTB4 and PGE2 synthesis were markedly decreased. When arachidonic acid was added to the cell suspension, it significantly stimulated LTB4 synthesis, especially in patients with active disease. Patients with active Crohn's disease or ulcerative colitis had moderately higher Ca2+ levels than healthy controls. However, there was a significant decrease in intracellular Ca2+ concentration in patients with quiescent disease who were receiving maintenance therapy. CONCLUSION: We suggest that increased LTB4 synthesis and elevated intracellular Ca2+ concentrations contribute to the pathophysiology of inflammatory bowel disease. Drugs effective in the treatment of these diseases may exert their pharmacological action by normalizing these pathological findings.

Aminosalicylic Acids↗
PubMed1994

[Venous post-thrombotic disease].

Venous post-thrombotic disease is a common complication of deep venous thrombosis of the lower limbs. Prevalence is around 75% after a five-year follow-up and 25% of these patients suffer from severe disorders. The clinical symptoms are non-specific and begin months or years after the acute thrombosis. The patients' claims range from uncomplicated oedema, leg cramps and superficial varicose veins to permanent skin changes (dermatitis, hypodermatitis, leg ulcers). Functional vascular exploration (continuous-wave Doppler, plethysmography, pulsed-wave echo-Doppler, exceptionally venography) allows a better knowledge of the haemodynamic consequences of the post-thrombotic disease: deep persistent truncular obstruction, partial or total recanalization, valvular incompetence and reflux in the deep veins, superficial varicose veins, incompetence of the perforating veins in the gaiter area, failure of the calf venous pump and microangiopathy.

Humans↗
PubMed1994

[Cough, vomiting, rapid weight loss].

A young male patient from Somalia presented with a productive cough since a few days, and he complained about vomiting after meals and a rapid loss of weight of 20 kg. Endoscopic, radiological and clinical examinations revealed a broncho-esophageal fistula. Further examinations showed mycobacterium tuberculosis as the underlying cause of the disease; a malignancy was excluded. Antituberculous treatment resulted in the loss of the present symptoms as well as in a clinical and endoscopic closure of the fistula.

Adult↗
PubMed1994

Safety and efficacy of lifibrol upon four-week administration to patients with primary hypercholesterolaemia.

The efficacy and safety of lifibrol, a novel cholesterol-lowering drug, was investigated in a double-blind clinical study in 168 patients with primary hypercholesterolaemia. Placebo and four lifibrol dose groups (150, 300, 450 and 600 mg/day) were tested over a period of 4 weeks. The mean LDL-cholesterol changes were 5.7%, -11.1%, -27.7%, -34.5% and -35.0%, respectively, after 4 weeks of treatment. No major changes in HDL-cholesterol were seen after this period. With the present study design, a decrease in triglycerides (-28%) was significant in the highest dosage group only. Additionally, it was shown that further independent risk factors for coronary heart disease were favourably influenced. Fibrinogen decreased in all dosage groups with a maximal mean value of 18% and a tendency toward reduction in lipoprotein (a) was observed in patients with high baseline levels (> 30 mg.dl-1). Lifibrol was generally well tolerated in all dosage groups and no serious adverse events were reported. Laboratory parameters did not show any clinically relevant alterations.

Anticholesteremic Agents↗
PubMed1994

The role of the spleen in the organ-specific metastasis of murine BW 5147 T lymphomas.

Organ-specific metastasis of tumour cells may result from selective invasion and growth or from selective host cell responses. The present study demonstrates how selective interactions with the host affect the metastatic pattern of two murine T cell hybridoma lines, derived from the BW 5147 thymoma. Upon intravenous inoculation into syngeneic mice BW-14 cells preferentially colonize the kidneys, whereas BW-19 cells metastasize mainly to the spleen and the liver. The organ-specific behaviour of the two cell lines appears to be determined by a differential interaction with the spleen microenvironment. Inoculation of BW-14 cells into splenectomized mice results in increased liver colonization, indicating a negative effect of the spleen on BW-14 tumour development in the liver. Macrophages are likely to be involved in this inhibition, since inoculation of BW-14 cells into macrophage-depleted mice also leads to increased liver and spleen metastasis. In contrast, inoculation of BW-19 cells into splenectomized mice results in decreased liver metastasis, which indicates that the spleen exerts a stimulating effect on BW-19 cells. Macrophages also appear to be involved in this stimulation, since macrophage depletion causes a similar decrease in liver and spleen colonization. Hence components of the splenic microenvironment, probably macrophages, exert inhibiting or stimulating activities on BW-14 or BW-19 cells respectively, thereby determining the subsequent liver or kidney colonization.

Animals↗
PubMed1994

Natriuretic peptides elevate cyclic 3',5'-guanosine monophosphate levels in cultured rat pinealocytes: evidence for guanylate cyclase-linked membrane receptors.

Cyclic GMP formation in the rat pinealocyte has generally been thought to involve guanylate cyclases (GC) which are activated via GTP-regulatory proteins following beta 1-adrenergic receptor stimulation. Recent studies have also pointed to a cytosolic GC in these cells whose activity can be elevated by nitric oxide donors. Little attention has been paid to the possibility that pinealocytes might express membrane-bound GC in the form of natriuretic peptide receptors. The present report demonstrates functional membrane GC in rat pinealocytes by (1) cross-linking analyses with radiolabelled atrial natriuretic peptide (ANP); (2) reverse transcriptase polymerase chain reaction (RT-PCR) and DNA blot hybridization with probes for both the GC-A and GC-B forms of the natriuretic receptor; and (3) monolayer cell cultures of pinealocytes, which accumulate cGMP in response to ANP and its related peptides. As the role for cGMP in the rat pineal gland does not appear to be directly coupled to the synthesis of melatonin, the natriuretic peptides may have other regulatory functions in this neuroendocrine tissue.

Affinity Labels↗
PubMed1994

Characterization of methionine-enkephalin release in the rat striatum by in vivo dialysis: effects of gamma-hydroxybutyrate on cellular and extracellular methionine-enkephalin levels.

The opioïd system is implicated in mediating the effects produced upon administration of gamma-hydroxybutyrate. Gamma-hydroxybutyrate occurs endogenously in the mammalian brain, and is most probably involved in the regulation of some basic brain functions, particularly those concerning the dopaminergic nigrostriatal pathway, which is closely linked to the expression of enkephalins in the striatum. In the present study, in vivo microdialysis was used to examine the basic characteristics of methionine-enkephalin (met-enkephalin) release in the striatum of Wistar rats, using a high performance radioimmunoassay. Administration of gamma-hydroxybutyrate to the rats induced a dose-dependent decrease in the extracellular release of met-enkephalin. In parallel, a dose- and time-dependent gamma-hydroxybutyrate-induced accumulation of met-enkephalin in striatum was observed. These two phenomena (tissue accumulation and inhibition of release) were blocked by NCS-382, a gamma-hydroxybutyrate receptor antagonist. The striatal met-enkephalin accumulation does not seem to be exclusively due to the inhibition of its release. Thus, a gamma-hydroxybutyrate mediating effect on met-enkephalin synthesis is suggested, most probably occurring via functional modulation of striatal dopamine synthesis and release. To understand the role of this dopaminergic mechanism, unilateral lesions of the nigrostriatal dopaminergic pathway were carried out. In gamma-hydroxybutyrate-treated rats, striata exhibited a similar increase in met-enkephalin content. In untreated rats, only the lesioned striatum showed an identical increase in met-enkephalin levels. Thus, striatal met-enkephalin accumulation could be attributed to the suppression of the dopaminergic impulse flow, due to gamma-hydroxybutyrate or to the action of 6-hydroxydopamine. In the extracellular spaces (microdialysis experiments), gamma-hydroxybutyrate administration induced identical modifications of met-enkephalin release in lesioned or non-lesioned striata. These modifications could be reproduced by peripheral or striatal administration of sulpiride, a D2/D3 antagonist. From a functional point of view, the dopaminergic D2 receptor blockade or the gamma-hydroxybutyrate-induced inhibition of dopamine release could be considered to induce similar results, with identical consequences on striatal met-enkephalin accumulation and release. These results suggest that gamma-hydroxybutyrate-induced modifications in met-enkephalin release, presumably potentiated by 6-hydroxydopamine treatment, act via a functional modification of the nigrostriatal dopaminergic pathway.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

From Plenck (d. 1807) to Dohi (d. 1931) and today: Austrian influence on Japanese dermatology.

The Vienna surgeon Joseph Plenck first listed individual skin lesions, some of which we consider primary efflorescences today. He wrote many more treatises, relating to different areas of medicine, most of which reached Japan. One century later Keizo Dohi wrote, that Plenck's oeuvre will remain unforgotten in the history of dermatology, for his importance, in general and for the close relation to the development of medicine and dermatology in Japan. A search for Japanese translations of Plenck's books could prove that. Dohi himself wanted to become a surgeon but changed his plans and enrolled in Moriz Kaposi's (1837-1902) department in Vienna as a postgraduate student in 1893. Sifting through Dohi's textbook and papers, the importance of the Hebra-Kaposi School for Japan is again explicitly stated by the Japanese master, who founded the Japanese Dermatological Society in December of 1900 and the disciplines's journal in 1901. The language of publication was German. Dohi's first paper appeared in the Archiv für Dermatologie und Syphilis in 1896, in German. In recent years Austrian dermatology has become influential again in dermatological research after a mid century low. A series of investigators have spent sabbatical years or postgraduate training at the former Hebra-Kaposi Department in Vienna. Their scientific achievements were mainly in the field of immunobiology of the skin. A list of publications and their authors is presented.

Austria↗
PubMed1994

Natriuretic peptides stimulate cyclic GMP production in an immortalized LHRH neuronal cell line.

The role of cyclic 3',5'-guanosine monophosphate (cGMP) as a second messenger in LHRH neurons is not well understood. Recent studies involving nitric oxide, a direct activator of soluble guanylate cyclase (GC), have implicated cGMP in the regulation of LHRH secretion both in vivo and in vitro. Evidence for the membrane-bound form of GC in LHRH neurons has thus far not been reported. In polymerase chain reaction screening of various cell lines for the natriuretic peptide receptors--which represent GCs--we identified both GC-A and GC-B cDNAs by southern blot hybridization in reverse transcribed and amplified extracts of the GT1-7 cell line, an immortalized LHRH neuronal cell line. Subsequent experiments demonstrated that all of the natriuretic peptides elevated cGMP production with a rank order of potency: CNP > ANP > BNP. Time course studies revealed a rapid intracellular accumulation of cGMP following exposure to CNP with a peak at 2.5 min. CNP was some 200-fold more potent than the NO donor, sodium nitroprusside, in stimulating cGMP accumulation in these cells. These data show for the first time the presence of functional mGCs on LHRH cells, and suggest that the natriuretic peptides may also participate in the regulation of LHRH activity.

Animals↗