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Biomedical subjects

C Unterberg

Publications and source records attributed to C Unterberg.

51 records · Page 3Linked to original sources

[Short- and long-term results following implantation of the new Wiktor stent in acute coronary occlusion following PTCA].

Ten patients, two women and eight men, were treated with the new balloon-expandable Wiktor Stent for acute coronary occlusion after PTCA. Two patients presented with an acute myocardial infarction. Stents with a diameter of 3.0 or 3.5 mm were implanted into the right coronary artery (n = 7), the left anterior descending (n = 2) artery, and the left circumflex coronary artery (n = 1). Stent implantation in the target segment was successful in all cases. Afterwards, patients received coumadine for 3 months and 100 mg acetylsalicyclic acid per day. We observed one acute occlusion after 8 h. Late occlusion occurred in two patients after cessation of anticoagulation within 3 weeks. Control angiography after 6 months in seven patients revealed stenosis within the stent in two cases.

Aged↗

[Excimer laser angioplasty in arterial obstructive disease. Clinical experience with guidewire-controlled catheter systems].

Percutaneous transluminal laser angioplasties (PTLA) were performed in nine patients (7 males, 2 females, aged 52-81 years) with peripheral vascular disease, stages IIB-IV (Fontaine's classification), with 75% stenosis (5 patients) or occlusion (4 patients) in the area of the superficial femoral artery. Two catheter systems were used. One was a monofiber catheter (600 microns) with eccentric guidewire, the other a multifiber catheter with 12 concentrically arranged fibres (200 microns each) and a central guidewire. An XeCl-excimer laser (308 nm), with a pulse duration of 50 ns and pulse frequency of 15-30 Hz, served as the laser source. It was possible in all patients to reduce the stenosis of 75-100% to 35-70% or reopen the occlusion without laser-associated complications. To remove the residual stenosis PTLA was followed by balloon dilatation in seven patients and by application of a Simpson atherectomy catheter in one patient: these measures reduced the degree of stenosis to 20-40%.

Aged↗

Subcellular distribution of cardiac fatty acid-binding protein in bovine heart muscle and quantitation with an enzyme-linked immunosorbent assay.

Several types of the 14-15 kDa fatty acid-binding proteins (FABPs) are known to occur in the cytosol of mammalian cells. With antibodies raised against the cardiac-type protein from bovine heart, immunoblots indicated a more widespread distribution of the cardiac FABP in subcellular fractions, such as mitochondria and nuclei. A detailed view was obtained when the post-embedding protein A-gold labeling method was applied to cross-sections of heart cells and isolated subcellular fractions. Cardiac FABP in myocytes was associated with myofibrils and localized within mitochondria and nuclei. After subfractionation of mitochondria, the binding protein was recovered with matrix proteins only. A non-competitive enzyme-linked immunosorbent assay (ELISA) of the direct type was developed specifically for bovine cardiac FABP. This assay was sensitive in the range of 0.05 to 1 ng, and concentrations of cardiac FABP per mg protein were found for cytosol, matrix and nuclei to be around 3.18, 0.18 and 0.03 micrograms, respectively. The newly found compartmentation of cardiac FABP in the heart cell must be considered when the true functions of the protein, yet to be defined, are studied.

Animals↗

[Excimer laser coronary angioplasty in high-grade stenoses and chronic occlusion].

Excimer-laser-angioplasty offers the advantage of minimal thermal injury to adjacent tissue compared to other laser ablation techniques. Highly flexible glass-fiber-catheter systems are now available, and are capable of transmitting sufficient energy densities to ablate even calcified atherosclerotic coronary plaques. We report initial results of excimer-laser-ablation of severe coronary stenoses and occlusions in 17 patients. An excimer-laser (308 nm) with a pulse duration of 50 ns and a repetition rate of 10 to 40 Hz served as laser source. Eight patients had a chronic total occlusion (RCA, n = 4, RCx, n = 3, LAD, n = 1), nine patients had 90% to 95% stenoses (LAD, n = 7, RCA, n = 2). In all cases a laser-catheter consisting of 17 circumferentially orientated 100 microns glass-fibers and a central 15/1000-inch lumen could be advanced to the stenoses/occlusion over a guidewire that had been passed across the stenoses/occlusion. Stenoses diameter could be reduced by 41.5 +/- 10.1% in all patients and vessel lumen was further increased by subsequent balloon dilatation in 10 cases. After 24 h, 16 vessels were patent and showed no restenoses; one recanalized RCA was found reoccluded. We observed no complications, such as perforation, spasm, or thrombi.

Aged↗

[Increased primary success rate in coronary angioplasty using a guide wire with attached balloon (microprobe)].

In 15 cases of 350 consecutive coronary angioplasties conventional low profile balloon catheters did not traverse the stenosis or occlusion over the guide-wire. A balloon on a wire device ("Microprobe", 2 mm) passed the stenosis or occlusion easily with a good primary result in 14 cases. The angioplasty procedure could then be completed with a larger standard balloon catheter. Use of the balloon on a wire device expands the technical facilities of angioplasty and increases the primary success rate in technically difficult cases.

Angioplasty, Balloon↗

Acute effects of the new angiotensin converting enzyme inhibitor ramipril on hemodynamics and carotid sinus baroreflex activity in congestive heart failure.

The hemodynamic effects of a single dose of 5 mg of ramipril, a new angiotensin converting enzyme inhibitor, were investigated in 10 patients with chronic congestive heart failure. Arterial blood pressure and total peripheral resistance were decreased by approximately 12% without causing reflex tachycardia. A highly significant decrease occurred in mean pulmonary artery and pulmonary capillary wedge pressures. These hemodynamic changes were equally pronounced at rest and during exercise on a bicycle ergometer; the effect was of the same magnitude 5 and 24 hours after medication. Angiotensin converting enzyme activity in plasma was nearly completely inhibited after 5 hours and remained at about 12% of control after 24 hours. Cardiac index, which was normal before treatment, remained unaffected. Thus, ramipril induced a balanced reduction of left ventricular pre- and afterload. The activity of the carotid sinus baroreflex was investigated in 8 of the patients using the neck suction technique before and 24 hours after ramipril. The reflex bradycardia during stimulation of the baroreceptors was significantly increased by ramipril, whereas the decrease in blood pressure remained essentially unaffected. Ramipril induced a selective sensitization of the parasympathetic baroreceptor heart rate reflex without influencing the sympathetically mediated peripheral vasodilatation. This effect may be responsible for the lack of reflex tachycardia in spite of the decrease in blood pressure.

Angiotensin-Converting Enzyme Inhibitors↗

Isolation and characterization of the fatty acid binding protein from human heart.

We have isolated in pure form a fatty acid binding protein (FABP) from human cardiac muscle. After preparation of a 100,000 g supernatant fraction, the procedure required only one gel chromatographic (Sephacryl S 200) and two cation exchange (CM-Sephadex C 50) steps. The recovery of FABP was 55%. Pure FABP (12.5 mg) was obtained from a 1-g of dry powder equivalent of the high-speed supernatant. The protein had an Mr of 15,500 +/- 1,000 Da and an isoelectric point of 5.3. The properties of human cardiac FABP, i.e., molecular mass, isoelectric point, amino acid composition, ultraviolet spectrum, and affinities for hydrophobic ligands, were close to those found for FABPs from bovine heart (Jagschies et al. 1985. Eur. J. Biochem. 152: 537-545). In addition, immunological cross-reactivities showed a relationship between FABPs from several mammalian heart tissues. The data elaborated by us and others support the existence of a cardiac-type FABP that is distinct from the well-defined hepatic-type and gut-type FABPs.

Amino Acids↗

Bovine fatty acid binding proteins. Isolation and characterisation of two cardiac fatty acid binding proteins that are distinct from corresponding hepatic proteins.

When a 100,000 X g supernatant from bovine heart was incubated with [1-14C]oleic acid and subjected to isoelectric focusing, two fatty acid binding proteins (FABPs) with isoelectric points at 4.9 and 5.1 were detected. The proteins were purified on a large scale first by heat and acid precipitation of a postmitochondrial supernatant, as well as fractionation with ammonium sulfate, then by alternate application of ion-exchange and gel chromatography. The procedure afforded around 60 mg pure proteins from 1.5 kg fresh heart muscle. Relative molecular masses of 15 300 +/- 1600 for both proteins were derived from sodium dodecyl sulfate/polyacrylamide gel electrophoresis, gel chromatography, sedimentation velocity as well as from amino acid analysis. Up to 50% of the proteins' secondary structures consisted of beta-sheet. N-termini of the peptide chains were blocked; the amino acid compositions of the two proteins were similar, but differed considerably from those of the two FABPs isolated from bovine liver [Haunerland et al. (1984) Hoppe Seyler's Z. Physiol. Chem. 365, 365-376]. Whereas hepatic FABPs changed their pI upon binding fatty acids, cardiac FABPs did not. Cardiac FABPs were immunologically identical, but did not cross-react with hepatic proteins. A reversible, concentration-dependent self-association reported for FABP from pig heart [Fournier et al. (1983) Biochemistry 22, 1863-1872] was not observed for FABP from bovine heart. Changes of concentration did not alter secondary structure, intrinsic fluorescence or the sedimentation coefficient of the protein.

Amino Acids↗

Physical activity decreases the number of beta-adrenergic receptors on human lymphocytes.

On intact human lymphocytes a specific binding site (BS) for 125I-Cyanopindolol (125I-CYP), a derivative of the beta-blocking drug pindolol, was characterized. Inhibition of binding for catecholamines in the following order of potency: l-isoprenaline greater than l-adrenaline greater than l-noradrenaline proves the BS as a beta 2-receptor subtype. In 77 healthy persons (36 females, 41 males) the number of BS amounted to 2,639 +/- 125 BS/cell without any significant correlation to age (17-86 years) or sex. The dissociation constant (KD) indicating the affinity of iodocyanopindolol to the BS on intact lymphocytes was KD = 1.9 +/- 1.1 X 10(-10) M. A change of the number of beta-adrenergic receptors on intact human lymphocytes has been measured previously in asthmatics and in the myocardium of patients with congestive heart failure. We investigated a possible change in the beta-receptors on lymphocytes by physical and mental activity ("stress") in physicians going about their daily routine work. Persons left alone in a hospital room reading or sleeping were defined as "inactive controls". The number of BS on intact lymphocytes was significantly higher in inactive persons at 8 a.m. (2,230 +/- 482 BS) compared to active persons (1,743 +/- 285 BS; P less than 0.05) and at 1 p.m. (2,394 +/- 253 BS vs 1,733 +/- 556; P less than 0.05) but not different at 6 p.m. (1,634 +/- 578 BS vs 1,768 +/- 588 BS; P less than 0.1). The KD remained unchanged under all conditions. The serum noradrenaline and adrenaline levels were also measured during the day.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Characteristics of fatty acid-binding proteins and their relation to mammary-derived growth inhibitor.

Based on sequence relationships the cytoplasmic fatty acid-binding proteins (FABPs) of mammalian origin are divided into at least three distinct types, namely the hepatic-, intestinal- and cardiac-type. Highly conserved sequences of FABPs within the same type correlate with immunological crossreactivities. Isoforms of hepatic-type FABP are found in several mammalian species and for bovine liver FABP specific shifts in isoelectric points upon lipidation with fatty acids are observed. Isoforms of intestinal-type FABP are not known and the occurrence of cardiac-type isoforms so far is confined to bovine heart tissue. A bovine mammary-derived growth inhibitor (MDGI) is 95% homologous to the cardiac-type FABP from bovine heart. Dissociation constants of FABP/fatty acid complexes are in the range of 1 microM and 1:1 stoichiometries are usually found, but the neutral isoform of hepatic FABP from bovine liver binds 2 fatty acids. On subcellular levels hepatic- and cardiac-type FABPs are differently distributed. Though mainly cytosolic in either case, immunoelectron microscopy as well as a gelchromatographic immunofluorescence assay demonstrate the association of hepatic FABP in liver cells with microsomal and outer mitochondrial membranes and with nuclei, whereas in heart cells cardiac FABP is confined to mitochondrial matrix and nuclei. In mammary epithelial cells MDGI is associated with neither mitochondria nor endoplasmic reticulum, and is expressed in a strictly developmental-dependent spatial and temporal pattern. The specific role proposed for MDGI is to arrest growth of mammary epithelial cells when they become committed to differentiation in the mammary gland.

Amino Acid Sequence↗

Antiproliferative effects of a c-myc antisense oligonucleotide on human arterial smooth muscle cells.

The effects of a c-myc antisense phosphorothioate DNA oligonucleotide were assessed on the proliferation rate of human arterial smooth muscle cells (HSMCs). Compared to a control oligonucleotide the antisense oligonucleotide suppressed the proliferation of HSMCs in a concentration-dependent manner without a major cytotoxic effect. Outgrowth of HSMCs from media explants was significantly inhibited as well. Induction of c-myc expression by serum stimulation of cells was blunted by the antisense oligonucleotide, as shown by immunoblotting. These results demonstrate that c-myc expression is an essential factor for proliferation of HSMCs after growth stimulation, and they show the potential of antisense technology for modulating gene expression of HSMCs in vitro.

Base Sequence↗

Proliferative response of human and minipig smooth muscle cells after coronary angioplasty to growth factors and platelets.

OBJECTIVES: Platelets aggregating at the site of angioplasty, shown to be a potent proliferative stimulus for cultured smooth muscle cells (SMC), could contribute to proliferation after angioplasty. METHODS: SMC were cultivated from human aorta and restenosed coronary lesions as well as from minipig aorta and from normal and post angioplasty coronary artery segments (n = 6 per source). 3H-thymidine incorporation was used as a measure of proliferation. RESULTS: 3H-thymidine incorporation varied greatly after passage 7 in all cell lines, but was significantly higher in SMC from human coronary restenosed lesions compared to those from human aorta and minipig coronary post angioplasty segments in passage 2 (44 +/- 6.4 x 10(3) cpm/5000 SMC vs 20 +/- 3.9 and 12.1 +/- 2.1). However, all SMC exhibited a dramatic increase of 3H-incorporation after passage 7. Growth factors stimulated 3H-thymidine incorporation either dose dependently (PDGF-BB and bFGF) or only very modestly (PDGF-AA, EGF, IGF-1). The most potent stimulation was seen with PDGF-BB, 50 ng/ml, and was 17 +/- 6% (human restenosed) and 16 +/- 8% (minipig post angioplasty) of the values observed after stimulation with 10% fetal calf serum. The most effective combination of growth factors, PDGF-BB (50 ng/ml) + bFGF(20 ng/ml) + IGF-1 (50 ng/ml), produced a 3H-thymidine incorporation of 44 +/- 10% (human restenosed) and 42 +/- 11% (minipig post angioplasty) of FCS values. Stimulation by isolated platelets was dose dependent and significantly higher: 75 +/- 19% and 70 +/- 15% of FCS values for those SMC. CONCLUSIONS: 1) SMC from all sources studied exhibit significant changes of proliferation with increasing passages, excluding the comparability of data obtained with cells in different passages. 2) Data obtained with SMC from any source might not apply for SMC from human coronary restenosed lesions. 3) Currently tested growth factors do not fully account for the proliferative effect of platelets on cultured SMC.

Adult↗

Oxygen free radical damage of isolated cardiomyocytes: comparative protective effect of radical scavengers and calcium antagonists.

Oxygen free radicals have been shown to play a major role in the development of perfusion abnormalities, contractile dysfunction, and irreversible injury in ischemic-reperfused myocardium. The aim of this study was to assess the direct protective effects of radical scavengers, calcium antagonists, and combination of these substances against free radical induced myocyte damage. Viability (% of rod-shaped cells) and adenine nucleotide content (AdN, high-pressure liquid chromatography) of isolated adult rat cardiomyocytes were measured after exposure to hypoxanthine (2 mM) and xanthine oxidase (25 mU/ml). After 90 min, viability of myocytes decreased to 4.2 +/- 3.4% (mean +/- SEM) of pre-exposure control, and AdN decreased from 28.2 +/- 1.8 to 8.09 +/- 1.1 nmol/mg protein. Addition of catalase (1500 U/ml) resulted in the preservation of viability (77 +/- 6% of pre-exposure control, n = 6, mean +/- SEM), and AdN 84 +/- 6%, p less than 0.001. These values are not significantly different from those measured in myocytes not exposed to free radicals (88 +/- 9% and 79 +/- 6%, respectively). Superoxide dismutase (2400 U/ml), dimethylthiourea (10 mM), and desferrioxamine (1 mM) did not preserve either viability or AdN. The calcium antagonist verapamil (10 microM) also preserved myocyte viability significantly (23 +/- 9.7%, p less than 0.05 vs unprotected cells), but failed to prevent the loss of AdN (13.2 +/- 4%, not significant as compared to unprotected cells). Viability and AdN in myocytes treated with nifedipine (10 microM) or diltiazem (10 microM) were not higher than in unprotected cells. All combined treatment forms which included catalase resulted in the preservation of myocyte viability as well as AdN. These data show that only the hydrogen peroxide scavenger catalase protects isolated cardiomyocytes against free radicals generated in the purine catabolic pathway.

Adenine Nucleotides↗