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Biomedical subjects

T Keller

Publications and source records attributed to T Keller.

At least 91 records · Page 5Linked to original sources

PGE1 and iloprost affect the high energy phosphates in the global ischemic and reperfused rat heart: a 31P-NMR study.

The influence of PGE1, iloprost and a combination of both on high energy phosphate levels in isolated rat hearts reperfused 1 h following 20 min of global ischemia was investigated employing 31P-NMR-spectroscopy. Whereas PGE1 induced a slight reduction in the decline of the creatine phosphate/inorganic phosphate. ATP/inorganic phosphate ratio and NMR-energetic index during ischemia, iloprost application was followed predominantly by a temporary but marked improvement of the creatine phosphate/inorganic phosphate ratio during the early period of reperfusion. The best results in preservation of high energy phosphates were achieved after simultaneous application of PGE1 and iloprost. It is presumed that the accelerated normalization of the heart function observed immediately after ischemia in the eicosanoid treated hearts is related to the more rapid recovery of intracardial high energy phosphate level.

Adenosine Triphosphate↗

Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate.

The generation of second messengers from the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PtdInsP2) by phosphoinositidase C has been implicated in the mediation of cellular responses to a variety of growth factors and oncogene products. The first step in the production of PtdInsP2 from phosphatidylinositol (PtdIns) is catalysed by PtdIns kinase. A PtdIns kinase activity has been found to associate specifically with several oncogene products, as well as with the platelet-derived growth factor (PDGF) receptor. We have previously identified two biochemically distinct PtdIns kinases in fibroblasts, and have found that only one of these, designated type I, specifically associates with activated tyrosine kinases. We have now characterized the site on the inositol ring phosphorylated by type I PtdIns kinase, and find that this kinase specifically phosphorylates the D-3 ring position to generate a novel phospholipid, phosphatidylinositol-3-phosphate (PtdIns(3)P). In contrast, the main PtdIns kinase in fibroblasts, designated type II, specifically phosphorylates the D-4 position to produce phosphatidylinositol-4-phosphate (PtdIns(4)P), previously considered to be the only form of PtdInsP. We have also tentatively identified PtdIns(3)P as a minor component of total PtdInsP in intact fibroblasts. We propose that type I PtdIns kinase is responsible for the generation of PtdIns(3)P in intact cells, and that this novel phosphoinositide could be important in the transduction of mitogenic and oncogenic signals.

1-Phosphatidylinositol 4-Kinase↗

Growth and premature leaf fall in American aspen as bioindications for ozone.

Several clones of the American aspen (Populus tremuloides Michx.) differing in ozone sensitivity were fumigated continuously for 105 days with different ozone concentrations, producing different ozone doses. The suitability of the clones as possible replacements for tobacco as bioindicators in forested areas was tested. The life span of leaves of the ozone-sensitive clones was distinctly reduced by ozone. The difference to controls was significant even in the relatively clean air at Birmensdorf. Growth was diminished, too, but the decrease in height was much less pronounced than that in weight. In sensitive clones an after-effect was detectable, since the weight of new shoots (grown from reserves) decreased with increasing ozone stress in the previous year. Since the tolerant clone grew less, it is-at first sight-of decreased economic interest from the point of view of rapid productivity. In the long run, however, it might be economically interesting because it may be able to maintain productivity (although at a lower level) due to better competitive strength.

Journal Article↗

Action of iloprost and PGE1 on global ischemic and reperfused myocardium: a 31P-NMR-study.

The influence of iloprost, PGE1 and of the combined application of iloprost and PGE1 on high energy phosphate contents was investigated in isolated rat hearts perfused aerob at 37 degrees C in Langendorff mode. Changes in creatine phosphate, ATP and inorganic phosphate were registered during 20 minutes of global ischemia and 56 minutes of reperfusion with 31P-NMR-spectroscopic methods starting drug application prior to ischemia simultaneously with onset of heart perfusion. Most effective in preservation of high energy phosphates was the combined application of PGE1 and iloprost resulting in a creatine phosphate/inorganic phosphate ratio of 103.2 +/- 30.9% of pre-ischemia values compared to 52.5 +/- 6.1% in control group without drug application 0-5 minutes after onset of reperfusion, 148.8 +/- 24.8% vs 78.8 +/- 15.2% at 6-11 minutes of reperfusion and 116.6 +/- 16% vs 68.9 +/- 12.7% at 12-17 minutes of reperfusion. The same trend was observed employing ATP/inorganic phosphate ratio. The improved energy state in reperfused hearts following application of PGE1 and iloprost in combination is presumed to be supported by a reduction of the loss of high energy phosphates (HEP) during global ischemia and by a cytoprotective effect of iloprost immediately after starting reperfusion.

Alprostadil↗

Fatigue fracture morphology in human lumbar motion segments.

The fatigue behavior of 17 fresh lumbar spine motion segments was examined during cyclic, axial, compressive loading. The loading frequency and magnitude were chosen to simulate vigorous physiological loading conditions. The average failure occurred after 318 such loading cycles. Two main types of failure occurred and both involved the endplate and the adjacent subchondral spongy bone of the vertebral body. A tendency was observed toward a relation between the degree of disk degeneration and fracture type. Location of the fatigue fractures corresponded to the location of earlier detected microcalluses of the spongy trabeculae in the vertebral body. The findings further demonstrated that, under repetitive physiological loading, the weakest part of the lumbar motion segment was the endplate and the adjacent spongy bone.

Adult↗

Effect of pentoxifylline on the ischemic rat kidney monitored by 31P NMR spectroscopy in vivo.

The effect of pentoxifylline on the recovery of renal energy metabolism after ischemia and reperfusion was studied by 31P nuclear magnetic resonance spectroscopy in vivo. Rat kidneys were exposed to 15, 30 and 60 min, respectively, of ischemia by clamping the arteria renalis. Pre-ischemic application of pentoxifylline improves the recovery of renal energy metabolism. The concentration of ATP was found to be higher in pentoxifylline pretreated kidneys than in controls after ischemia. The 5'-nucleotidase inhibiting activity of pentoxifylline is suggested to be the mechanism responsible for the protective effect of the drug. 31P NMR spectroscopy proved to be a powerful tool for continuous follow-up of drug effects on metabolic processes.

Adenine Nucleotides↗

31-P-NMR-spectroscopy on ischemic and reperfused rat hearts: effects of iloprost.

Effects of iloprost on the behaviour of high energy phosphate contents were investigated in global ischemic and reperfused rat hearts prepared according to Langendorff. Iloprost application before and after 20 min of ischemia at a dosage of 9-12 pg/g heart weight x min improved the availability of high energy phosphates as was shown by CP/Pi ratio during the first hour of reperfusion.

Animals↗

[Experiences and materials on internal sectorization of large psychiatric hospitals].

The city of Bremen is divided into 5 catchment areas ("sectors") for the care of psychiatric patients. Internal sectorization of the mental hospital was introduced by relating certain wards to certain catchment areas. The development of internal sectorization and its impact on the diagnostic and therapeutic work in the hospital as well as on the cooperation with external services is described. Some data on patient flows are given. In addition we report on the results of an inquiry in psychiatric hospitals regarding sectorization and other forms of community oriented psychiatric care in the Federal Republic of Germany. The literature on sectorization as one principle of community psychiatry is overviewed.

Combined Modality Therapy↗

The electrical conductivity of Norway spruce needle diffusate as affected by certain air pollutants.

Four-year-old potted Norway spruce (Picea abies (L.) Karst.) grafts established with scion material from three mature trees, were exposed to either long-term fumigation with SO(2), with and without water stress, or long-term ozone fumigation. The electrical conductivity of the needle diffusate was measured after the needles had been washed with chloroform and then leached in distilled water. Although none of the treatments caused visible symptoms of injury, SO(2) fumigation and water stress both caused an increase in diffusate conductivity, but the effects were not synergistic. Ozone fumigation lowered both conductivity and nutrient ion concentration in the leachate.

Journal Article↗

[Significance of the ejection fraction at rest and by stress using radionuclide ventriculography for the prognosis of myocardial infarct patients--comparison with other study methods].

We examined 221 patients with postmyocardial infarctions 8 weeks after MI using radionuclide ventriculography (RNVA) at rest (EFR) and during supine submaximal exercise (delta EF). Mortality rates were evaluated 2 1/2 and 3 1/2 years later by interviewing patients and/or their homephysicians. Sixteen patients were dead (6.7%) 2 1/2 years after MI, 28 (12.7%) were dead after 3 1/2 years. Thirty percent of patients with a resting EF less than 30% had died 2 1/2 years after MI, and 40% were dead within 3 1/2 years. The mortality rate was significantly higher than in patients who had EF greater than or equal to 30% 8 weeks after MI. Patients with a decrease of delta EF (greater than or equal to 5%) showed a 2 1/2 year mortality of 10.8% and after 3 1/2 years of 18.5%. Mortality was significantly higher in patients with decreasing EF during exercise than in those who increased their EF during exercise. This prognostic value of EFR and delta EF was compared with other parameters (angina pectoris, ECG at rest and during exercise, heart volume, Holter ECG, floating catheter PCP [rest and exercise], coronary angiography). Radionuclide ventriculography at rest and during exercise showed a tendency to be the best determining factor for prognosis, and is therefore recommended to determine prognosis in post-MI patients.

Adult↗

High-affinity microtubule protein-higher organism DNA complexes. Many-fold enrichment in repetitive mouse DNA sequences comprised of satellite DNAs.

We have examined aspects of the interaction of cycled microtubule protein preparations with 35S-labeled mouse DNA tracer in a competition system with unlabelled competitor E. coli or mouse DNA. The nitrocellulose filter binding assay was used to measure interaction by scintillation counting. DNA molecular weight affected the levels of filter retained 35S-labelled mouse tracer DNA. Filter retention levels increased if 35S-labelled mouse DNA tracer size was increased, and the filter binding level decreased if competitor DNA size was increased. There was a sizeable, reproducible difference in the 35S-labelled mouse DNA tracer binding level of about 1% when E. coli or mouse DNA competitors were compared. Mouse DNA more effectively competed with 35S-labelled mouse DNA for microtubule protein binding than did E. coli DNA, suggesting that a small class of higher-organism DNA sequences interacts very strongly with microtubule protein. From other studies we know this to be the MAP fraction (Marx, K.A. and Denial, T. (1984) in The Molecular Basis of Cancer (Rein, R., ed.), Alan R. Liss, New York, in the press; and Villasante, E., Corces, V.G., Manso-Martinez, R. and Avila, J. (1981) Nucleic Acids Res. 9, 895-908). We find that this difference in competitor DNA strength is qualitatively similar under high-stringency conditions (0.5 M NaCl, high competitor [DNA]) we developed for examining high-affinity complexes. Under high-stringency conditions we isolated 1.2% and 0.6% of 35S-labelled mouse DNA at 4200 and 350 bp respective sizes as nitrocellulose filter bound DNA-protein complexes. At both molecular weights these high-affinity DNA sequences, isolated from the filters, were shown to be significantly enriched in repetitive DNA sequences by S1 nuclease solution reassociation kinetics. The kinetics are consistent with about a 4-fold mouse satellite DNA enrichment as well as enrichment in other repetitious DNA sequence classes. The high molecular weight filter-bound DNA samples were sedimented to equilibrium in CsCl buoyant density gradients and found to contain primarily mouse satellite DNA density sequences (1.691 g/cm3) with some minor fractions at other density positions (1.670, 1.682, 1.705, 1.740, 1.760 g/cm3) similar to those observed by our laboratory in previous investigations of micrococcal nuclease-resistant chromatin (Marx, K.A. (1977) Biochem. Biophys. Res. Commun. 78, 777-784). That the high-affinity microtubule-bound DNA was some 3-5-fold enriched in mouse satellite sequences was demonstrated by its characteristic BstNI restriction enzyme cleavage pattern.

Animals↗

Studies on the spectrin-like protein from the intestinal brush border, TW 260/240, and characterization of its interaction with the cytoskeleton and actin.

The terminal web of the intestinal brush border contains a spectrin-like protein, TW 260/240 (Glenney, J. R., Jr., P. Glenney, M. Osborne, and K. Weber, 1982, Cell, 28:843-854.) that interconnects the "rootlet" ends of microvillar filament bundles in the terminal web (Hirokawa, N., R. E. Cheng, and M. Willard, 1983, Cell, 32:953-965; Glenney J. R., P. Glenney, and K. Weber, 1983, J. Cell Biol., 96:1491-1496). We have investigated further the structural properties of TW 260/240 and the interaction of this protein with actin. Salt extraction of TW 260/240 from isolated brush borders results in a loss of terminal web cross-linkers primarily from the apical zone directly beneath the plasma membrane. Morphological studies on purified TW 260/240 using the rotary shadowing technique confirm earlier results that this protein is spectrin-like and is in the tetrameric state in buffers of low ionic strength. However, examination of TW 260/240 tetramers by negative staining revealed a molecule much straighter and more uniform in diameter than rotary-shadowed molecules. At salt concentrations at (150 mM KCl) and above (300 mM KCl) the physiological range, we observed a partial dissociation of tetramers into dimers that occurred at both 0 degree and 37 degrees C. We also observed (in the presence of 75 mM KCl) a concentration-dependent self-association of TW 260/240 into sedimentable aggregates. We have studied the interaction of TW 260/240 with actin using techniques of co-sedimentation, viscometry, and both light and electron microscopy. We observed that TW 260/240 can bind and cross-link actin filaments and that this interaction is salt- and pH-dependent. Under optimum conditions (25-75 mM KCl, at pH 7.0) TW 260/240 cross-linked F-actin into long, large-diameter bundles. The filaments within these bundles were tightly packed but loosely ordered. At higher pH (7.5) such bundles were not observed, although binding and cross-linking were detectable by co-sedimentation and viscometry. At higher salt (greater than 150 mM KCl), the binding of TW 260/240 to actin was inhibited. The presence of skeletal muscle tropomyosin had no significant effect on the salt-dependent binding of TW 260/240 to F-actin.

Actins↗

Microsurgical vascular anastomosis for traumatic middle cerebral artery occlusion.

A unique case is reported in which extracranial to intracranial arterial anastomosis was used to treat persisting traumatic middle cerebral artery occlusion. The rationale and indications for use of cerebral revascularization are discussed. Trauma surgeons are encouraged to consider extracranial to intracranial anastomosis in patients with cerebrovascular occlusion inappropriate for operations in the neck.

Adult↗