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Biomedical subjects

G Zimmer

Publications and source records attributed to G Zimmer.

At least 19 recordsLinked to original sources
PubMed1995

Decrease of red cell membrane fluidity and -SH groups due to hyperglycemic conditions is counteracted by alpha-lipoic acid.

Human red cell membranes (ghosts) were treated by 5 min of incubation with fasting or hypo- and hyperglycemic concentrations of D-glucose. This simulation of nondiabetic or diabetic conditions revealed an influence on membrane fluidity and on protein -SH reactivity. Protein -SH groups, measured with Ellman's reagent, generally behave in the same way as membrane fluidity determined with diphenylhexatriene. Maximal values were obtained with 5 mM D-glucose, whereas decrease was observed above 10 mM D-glucose. Addition of alpha-lipoic acid (4 nmol/mg protein) resulted in a significant increase in membrane fluidity and titratable -SH groups at glucose concentrations of 10 mM and above. Dithiothreitol diminished titrable-SH groups and did not restore membrane fluidity. 2-Mercaptopropionylglycine was only effective in restoration of -SH groups. By contrast to D-glucose, other sugars such as L-glucose, D-fructose, or sucrose revealed no comparable changes on membrane fluidity and titratable membrane -SH groups between concentrations of 5 and 10 mM. The hyperglycemic effects of D-glucose were corroborated with isolated, reconstituted membrane proteins and erythrocyte glucose carrier, indicating that, in general, the observed divergent biochemical/biophysical changes of the red cell membrane are influenced by the glucose transport protein GluT1. The natural R-form and the S-form of alpha-lipoic acid were compared with racemic R-/S-forms for their efficiencies in alterations of red cell membrane fluidity. Decreased fluidities in presence of 10 mM glucose were found to be influenced in differentiated ways: the S-form was highly active in increasing fluidity at 4 nmol/mg and increasingly less active up to 20 nmol/mg protein. By contrast the R-form of lipoic acid was moderately efficient in increasing fluidity through a larger concentration range between 4 and 80 nmol/mg protein.

Dithiothreitol↗
PubMed1995

ATP synthesis by purified ATP-synthase from beef heart mitochondria after coreconstitution with bacteriorhodopsin.

An ATP-synthase complex active in ATP synthesis was isolated from beef heart mitochondria by solubilization of submitochondrial particles with dodecyl-beta-D-maltoside and purified in a one-step procedure by subsequent ion-exchange chromatography. The electrophoretic analysis resulted in 14 subunits for the F0 F1 complex. ATP hydrolysis activity of the purified enzyme was 25 mumol ATP min-1 mg-1F0F1. ATP hydrolysis could be stimulated by addition of lipid vesicles. Further stimulation was observed in the presence of uncoupler. The inhibitors dicyclohexylcarbodiimide and oligomycin reduced hydrolytic activity to 70 and 40%, respectively. The preservation of ATP synthesis capability was demonstrated by reconstitution of the purified enzyme together with the light-driven proton pump bacteriorhodopsin. Upon illumination of ATP-synthase/bacteriorhodopsin proteoliposomes ATP synthesis activity was detectable for at least 7 min. At reduced temperature this time could be increased to 20 min. The maximum synthesis rate of 58 nmol ATP min-1 mg-1 F0F1 was obtained after reconstitution into liposomes made from crude soy bean lecithin by a detergent dialysis procedure using octyl-beta-D-glucopyranoside and monomeric bacteriorhodopsin. ATP synthesis was partially inhibited by oligomycin or dicyclohexylcarbodiimide and was completely abolished in the presence of uncoupler. The ability of the purified enzyme to synthesize ATP shows that the described isolation procedure results in an ATP-synthase complex which is intact in structure and function.

Adenosine Triphosphate↗
PubMed1995

Identification of a 40-kDa cell surface sialoglycoprotein with the characteristics of a major influenza C virus receptor in a Madin-Darby canine kidney cell line.

Infection of cells by influenza C virus is known to be initiated by virus attachment to cell surface glycoconjugates containing N-acetyl-9-O-acetylneuraminic acid. Using an in vitro virus binding assay, we have detected this carbohydrate on several glycoproteins of Madin-Darby canine kidney cells (type I), a polarized epithelial cell line permissive for infection with influenza C virus. Among these proteins, only one was found to be present to a significant extent on the cell surface. This protein, gp40, was characterized as an O-glycosylated (mucin-type) integral membrane protein of 40 kDa, which was predominantly localized on the apical plasma membrane of filter-grown cells. It is a major cell surface sialoglycoprotein in this cell line and was shown to be subject to constitutive and rapid endocytosis. Thus, this glycoprotein can mediate not only the binding of influenza C virus to the cell surface, but also its delivery to endosomes, where penetration occurs by membrane fusion. Other highly sialylated cell surface glycoproteins were also detected but did not mediate influenza C virus binding to a significant extent, indicating that only gp40 contains 9-O-acetylated sialic acids.

Animals↗
PubMed1995

Residual 201Tl activity in irreversible defects as a marker of myocardial viability. Clinicopathological study.

BACKGROUND: The objective of the present study was to characterize the relation between the residual 201Tl activity in irreversible perfusion defects and the extent of irreversible myocardial damage indicated by the volume fraction of myocardial interstitial fibrosis in patients with chronic coronary artery disease. METHODS AND RESULTS: Stress planar 201Tl scintigraphy with tracer reinjection at rest was performed in 37 patients with > or = 75% stenosis of the left anterior descending coronary artery, and anteroseptal 201Tl activity was quantified by computer-assisted placement of regions of interest from the serial myocardial images. During coronary artery bypass grafting (performed within 6 +/- 3 weeks after scintigraphy), two transmural biopsy specimens were taken from the anterior wall of the left ventricle and the amount of interstitial fibrosis was assessed by use of light microscopic morphometry. A wide spectrum of interstitial fibrosis was obtained, ranging from 15 vol% to 60 vol%. Interstitial fibrosis was similar in patients with reversible (n = 11) or irreversible (n = 15) tracer defects in conventional stress-redistribution images. However, interstitial fibrosis was significantly lower in patients who had enhanced regional 201Tl activity after tracer reinjection compared with those who did not have enhancement of tracer activity after reinjection (28 +/- 8 vol%, n = 7, versus 41 +/- 12 vol%, n = 8; P = .031). The correlation between relative poststenotic 201Tl activity and interstitial fibrosis after tracer reinjection was significantly improved compared with conventional redistribution images (r = -.622 versus r = -.851, n = 15; P < .01). CONCLUSIONS: The present data demonstrate that the level of regional 201Tl activity in redistribution and, in particular, reinjection images is significantly related to the mass of preserved viable myocytes in poststenotic left ventricular myocardium. Therefore, the residual 201Tl activity provides information about viability within irreversible perfusion defects and may itself serve as marker of myocardial viability.

Biopsy↗
PubMed1995

The influence of age on injury severity of restrained front seat occupants in head-on collisions.

This excerpt is part of a large-scale retrospective study on the interrelationship between accident severity and injury severity. A multivariate analysis of 319 cases of restrained front seat occupants involved in car-to-car head-on collisions showed the significant influence of the energy equivalent speed (EES) and age of the occupants on the number of rib fractures and sternum fractures. Three hundred occupants sustained no rib fractures, nine occupants one to 16 rib fractures, and ten occupants 17 to 32 rib fractures. In these three groups the EES increased from 35 km/h (no rib fractures) to 55 km/h (one to 16 rib fractures) and to then to 67 km/h (17 to 32 rib fractures). The average age in these groups was 34, 55 and 57 years respectively. Twenty-four occupants sustained sternum fractures. The average values of the EES and the average age were: in the group with sternum fractures: 56 km/h; 50 years old; in the group without sternum fractures: 35 km/h; 34 years old. The probability of sustaining fatal injuries in a head-on collision depended on the EES as well as the age of the occupant. At an EES of 60 km/h the probability of fatal injuries was 0.05% in the group < 30 years and 35% in the group > 59 years. Fifty-eight per cent of the occupants with sternal fractures had rib fractures as well; 46% of the occupants with rib fractures also had sternal fractures. The results were compared to the results of 185 post-mortem simulations of head-on collisions from the year 1973 to 1978. In post-mortem simulations the number of rib fractures and sternum fractures was influenced by vehicle decelerations and the age of the test subjects. The number of rib fractures increased at higher collision speeds, higher decelerations and increased age; the number of sternum fractures increased at higher deceleration and increased age of the test subjects. Seventy-two per cent of the test subjects with sternal fractures had rib fractures; 91% of the subjects with rib fractures had sternal fractures.

Accidents, Traffic↗
PubMed1994

[Life threatening complications in alternative medicine--problems in patient education].

The risk of treatment offered by nonmedical practitioners are demonstrated with six casuistic expertise reports. In four cases the treatment had a lethal outcome, because the underlying illnesses had been underestimated or had not been diagnosed. To the authors opinion a patient's consent in a treatment by nonmedical practitioners is inoperative, because a nonmedical practitioner is on principle unable to inform a patient regularly because of his lack of medical knowledge.

Adult↗
PubMed1994

Modification of sialic acids by 9-O-acetylation is detected in human leucocytes using the lectin property of influenza C virus.

Influenza C virus spike glycoprotein HEF specifically recognizes glycoconjugates containing 9-O-acetyl-N-acetylneuraminic acid. The same protein also contains an esterase activity. Taking advantage of these two properties, influenza C virus was used as a very sensitive probe for the detection of traces of 9-O-acetyl-N-acetylneuraminic acid in human leucocytes. The binding of influenza C virus to leucocyte glycoproteins and gangliosides separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and thin-layer chromatography, respectively, was assayed using a chromogenic esterase substrate. In this way, glycoproteins of B-lymphocytes and T-lymphocytes were found to contain 9-O-acetylated sialic acids. Of the various 9-O-acetylated gangliosides detected, one had the characteristics of 9-O-acetylated GD3. The identification of 9-O-acetylated sialic acids on distinct glycoproteins and glycolipids should be helpful in assigning a physiological role to this sugar.

Acetylation↗
PubMed1994

Reperfusion injury in skeletal muscle: interaction of osmotic and colloid-osmotic pressure in the initial reperfusate for oedema prevention.

Previous studies from the authors' laboratory have shown that controlled limb perfusion after prolonged, acute ischaemia minimizes reperfusion injury. The present study was performed to investigate the role of osmotic and colloid-osmotic pressure in the initial reperfusate in order to reduce postischaemic limb oedema and subsequent reperfusion injury. A total of 96 isolated rat hindlimbs were used: 18 were perfused immediately after amputation (no ischaemia; untreated) and 78 limbs were subjected to 4 h of warm ischaemia in a moist chamber. Thereafter eight limbs were used to investigate the effects of the addition of mannitol to the initial reperfusate. The remaining 70 limbs received controlled reperfusion (modified reperfusate with various osmotic (315-580 mosmol/l) and colloid-osmotic pressure (0-50 mmHg. perfusion pressure 50 mmHg) during the first 30 min after ischaemia. Controlled reperfusion was always followed by uncontrolled reperfusion (30 min. perfusion pressure 100 mmHg) to simulate the clinical condition where normal blood perfusion at systemic pressure will follow controlled reperfusion. Functional recovery, limb weight, water content of the soleus muscle, limb flow and tissue high-energy phosphates were assessed at the end of the experiment. Results show that a reperfusate without colloid-osmotic pressure (i.e. without macromolecules) produces severe limb oedema (84.6(2.0)% water content) and allows no functional recovery after prolonged warm ischaemia. Addition of mannitol to the initial reperfusate does not prevent severe reperfusion injury. In contrast, a hyperosmotic reperfusate with a colloid-osmotic pressure of 26 mmHg effectively prevents limb oedema (78.6(0.9)% water content, 110.8(2.4)% of control weight). Physiological osmotic pressure (315 mosmol/l), however, will not reduce oedema formation (82.7(0.4)% water content). Furthermore, colloid-osmotic pressure > 26 mmHg increases the viscosity of the reperfusate (flow decreases to < 50% of control) and does not allow an optimal functional recovery. Macromolecules used to create the colloid-osmotic pressure should be of similar molecular weight to albumin (69,000 Da); those with a smaller molecular weight (e.g. hydroxyethyl starch40,000/0.5) produce excessive limb oedema (184.9(13.5)% control weight; 85.7(1.4)% water content) without functional recovery (0% control contractions). The present data suggest that after prolonged limb ischaemia: (1) addition of mannitol to a crystalloid solution does not prevent oedema; (2) hyperosmotic reperfusates (380-480 mosmol/l) with a colloid-osmotic pressure of 26 mmHg are most effective in preventing limb oedema; and (3) macromolecules used to achieve colloid-osmotic pressure should have a molecular weight similar to albumin.

Animals↗
PubMed1994

Reperfusion injury in skeletal muscle: controlled limb reperfusion reduces local and systemic complications after prolonged ischaemia.

Previous studies in isolated limbs using crystalloid perfusion solutions have shown that control of the initial reperfusion reduces postischaemic complications. However, no experimental study has been undertaken to evaluate the concept of controlled limb reperfusion experimentally in an in vivo blood-perfused model and to assess the local as well as systemic effects of normal blood reperfusion and controlled limb reperfusion. Of 20 pigs undergoing preparation of the infrarenal aorta and iliac arteries, six were observed for 7.5 h and served as controls; 14 others underwent 6 h of complete infrarenal occlusion. Thereafter, embolectomy was simulated in eight pigs by removing the aortic clamp and establishing normal blood reperfusion at systemic pressure. In six other pigs, the composition of the reperfusate and the conditions of reperfusion were controlled during the first 30 min, followed by normal blood reperfusion. Some 6 h of infrarenal aortic occlusion leads to a severe decrease in high-energy phosphates and muscle temperature, together with a slight increase in creatine kinase and potassium in the systemic circulation. Normal blood reperfusion resulted in severe reperfusion injury: massive oedema developed, the tissue showed a marked decrease in oxygen consumption, glucose consumption, tissue ATP, total adenine nucleotides, muscle pH and total calcium in the femoral vein. Furthermore, a massive increase was seen in plasma creatine kinase concentration and potassium, together with the development of muscle rigidity. In sharp contrast, initial treatment of the ischaemic skeletal muscle by controlled limb reperfusion resulted in normal water content, oxygen consumption, glucose consumption, flow and muscle rigidity. Furthermore, controlled limb reperfusion resulted in higher total adenine nucleotides content, less tissue acidosis, markedly reduced creatine kinase release, and potassium release as compared with that of normal blood reperfusion. This study shows that 6 h of acute infrarenal aortic occlusion will result in severe reperfusion injury (postischaemic syndrome) if normal blood at systemic pressure is given in the initial reperfusion phase. In contrast, initial treatment of the ischaemic skeletal muscle by controlled limb reperfusion reduces the metabolic, functional and biochemical alterations.

Acute Disease↗
PubMed1994

Penetration of spin-labeled dihydrolipoate into the skin of hairless mice. Modification of epidermal and dermal polarity.

Electron paramagnetic resonance (EPR) imaging with the modulated field gradient technique is a novel method to investigate skin biophysical and biochemical properties employing specific nitroxide spin probes. Using this method, a distinct increase in polarity from epidermis towards lower dermis is observed with the spin label dit-butylnitroxide (DTBN). With proxylmaleimide a considerable increase in mobility is found, when epidermis is compared with dermal compartments. The effect of the natural antioxidant dihydrolipoate on skin membrane polarity was studied. Skin penetration of spin labeled dihydrolipoate was investigated by EPR imaging. The results indicate that dihydrolipoate also increases membrane polarity. The biophysical and biochemical changes in the epidermis and dermis as revealed by spatial imaging, provide indirect evidence for skin penetration of dihydrolipoate. This conclusion was supported by the finding that spin labeled derivatives of dihydrolipoate and lipoate were detected inside epidermis and dermis by EPR imaging. This study demonstrates the feasibility of EPR imaging to investigate pharmacodynamic and pharmacokinetic properties of spin labeled drugs in skin.

Animals↗
PubMed1993

Purification of ATP synthase from beef heart mitochondria (F0F1) and co-reconstitution with monomeric bacteriorhodopsin into liposomes capable of light-driven ATP synthesis.

ATP synthase was isolated from beef heart mitochondria by extraction with N,N-bis-(3-D-gluconamidopropyl)deoxycholamide or by traditional cholate extraction. The enzyme was purified subsequently by ion-exchange and gel-permeation chromatographies in the presence of glycerol and the protease inhibitor diisopropylfluorophosphate. The ATP synthase consisted of 12-14 subunits and contained three tightly bound nucleotides. The co-reconstitution of crude or purified ATP synthase with monomeric bacteriorhodopsin by the method of detergent incubation of liposomes yielded proteoliposomes capable of light-driven ATP synthesis, as detected with a luciferase system for at least 30 min. The reaction was suppressed by the inhibitors oligomycin (> 90%) and dicyclohexylcarbodiimide (85%) and by the uncoupler carbonylcyanide-p-trifluormethoxyphenylhydrazone (> 95%). The purified ATP synthase was apparently free of cytochrome impurities and of adenylate kinase activity, i.e. the enzyme exhibited light-driven ATP synthesis without the dark reaction. For the first time, this is demonstrated with purified ATP synthase from beef heart mitochondria.

Adenosine Triphosphate↗
PubMed1993

Cardiac recovery during post-ischemic reperfusion is improved by combination of vitamin E with dihydrolipoic acid.

Effects of dietary vitamin E supplementation in rats were studied to determine whether or not they have a higher tolerance against cardiac ischemia-reperfusion injury using the working or Langendorff heart systems. Also, dihydrolipoic acid, recently reported to have potent antioxidant properties and accelerate vitamin E recycling of membrane in vitro, was perfused into the heart model systems to investigate its in vivo relationship with vitamin E. Tissue vitamin E content was increased by vitamin E feeding, but heart preparations did not show any improved functional recovery. Control hearts perfused with dihydrolipoic acid also did not show any improvement. However, a synergistic response is observed with the combination of dihydrolipoic acid perfusion and high dietary vitamin E using both perfusion systems in improvement of cardiac recovery. These results indicate that a high concentration of myocardial vitamin E does not increase tolerance to ischemia-reperfusion injury by itself, but, the combination of exogenous dihydrolipoic acid and high endogenous vitamin E can produce synergistic protective effects on recovery from ischemia during reperfusion.

Analysis of Variance↗
PubMed1993

Cathepsin D as a vitality marker in human skin wounds.

This paper shows the results obtained by studying the lysosomal enzyme Cathepsin D as a potential marker for the vitality of wounds in human specimens. We have analyzed 53 samples using enzymological and histological techniques. Our results show the ability of Cathepsin D to establish the vital origin of wounds inflicted 5 minutes or less before death, where the specific activity of cathepsin D reached 0.055 units at the wound edge and 0.01 units in their respective controls (P < 0.001). As previously demonstrated in an experimental series, Cathepsin D seems to be a very useful marker of high forensic interest in especially difficult cases. Further studies are in progress to check the influence of different factors such as drugs intake and clinical conditions on Cathepsin D activity.

Adolescent↗
PubMed1993

Surface glycoprotein of influenza C virus: inactivation and restoration of the acetylesterase activity on nitrocellulose.

The influenza C glycoprotein HEF was analyzed for acetylesterase activity after SDS-polyacrylamide gel electrophoresis and transfer to nitrocellulose membranes. Using a histological esterase assay, the glycoprotein was detected as a colored band indicating that it is enzymatically active. The enzyme activity was not affected by low pH, but was abolished after denaturation by SDS as well as after breaking the disulfide bonds by reducing agents. Glycoprotein inactivated by SDS regained its enzyme activity if the ionic detergent was displaced by either bovine serum albumin or a nonionic detergent. The stability of the enzyme combined with the color assay provides a convenient tool to study the acetylesterase activity of the influenza C virus glycoprotein.

Acetylesterase↗
PubMed1993

Nitroxide radical biostability in skin.

Nitroxide radicals are important chemical tools in dermatologic research (e.g., for studying biophysical properties of skin lipids and epidermal membranes with the method of electron paramagnetic resonance, EPR, spectroscopy). However, nitroxides may loose their paramagnetic properties in biological tissues, which could limit their usefulness in biomedical applications. We analyzed the biostability of various chemical types of nitroxide radicals in keratinocytes, epidermis homogenate, and intact skin. EPR signal loss of imidazoline, pyrrolidine, piperidine, and oxazolidine nitroxides is attributed to their reduction to the corresponding hydroxylamine. The rate of nitroxide reduction in skin varies considerably with nitroxide ring structure and substitution. The order of nitroxide stability in isolated human keratinocytes, mouse epidermis homogenate, and intact mouse and human skin is imidazoline > pyrrolidine > di-t-butylnitroxide (DTBN) > piperidine > oxazolidine. Cationic nitroxides are reduced much faster than neutral or anionic probes, presumably due to transmembrane electron shuttle or internalization. The results indicate that imidazoline- and pyrrolidine-type nitroxides should be used when high biostability of nitroxides is needed. Piperidine-type nitroxides are versatile probes for studying one-electron transfer reactions in skin.

Animals↗
PubMed1992

Decreased concentration of myofibrils and myofiber hypertrophy are structural determinants of impaired left ventricular function in patients with chronic heart diseases: a multiple logistic regression analysis.

OBJECTIVES: The aim of this study was to perform a multiple logistic regression analysis to identify independent structural determinants of impaired left ventricular function. BACKGROUND: The association between contractile failure and structural alterations of the myocardium has been demonstrated in several studies, and multiple interactions between myocardial structure and cardiac performance are likely. METHODS: Morphometric data assessed from 130 left ventricular biopsy specimens were analyzed. The endomyocardial specimens were obtained from 57 patients with normal coronary arteries (17 with normal left ventricular ejection fraction and 40 with impaired left ventricular function [dilated cardiomyopathy]), 15 patients with hypertrophic cardiomyopathy and 32 patients with aortic valve disease. Transmural biopsy specimens were assessed in 6 donor hearts before heart transplantation and in 20 patients with left anterior descending coronary artery disease whose specimens were obtained from the left ventricular anterior wall during aortocoronary bypass surgery. Global or regional left ventricular function was evaluated from left cineventriculograms. The volume fraction of cardiac fibrous tissue, intracellular volume fraction of myofibrils, volume fraction of myofibrils related to myocardial tissue (including fibrosis) and myofiber diameters were determined from semithin sections of the biopsy specimens with the use of light microscopic morphometry. RESULTS: Multiple logistic regression analysis revealed decreased volume fraction of myofibrils (p < 0.005) and increased fiber diameter (p < 0.002) as independent determinants of impaired left ventricular function. CONCLUSIONS: These data indicate that, independent of the underlying heart disease, both decreased concentration of contractile proteins and myocyte hypertrophy are independently associated with impaired left ventricular function.

Age Factors↗