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Biomedical subjects

G Zimmer

Publications and source records attributed to G Zimmer.

At least 109 records · Page 6Linked to original sources
PubMed1990

Influence of pH on sulfhydryl groups and fluidity of the mitochondrial membrane.

Fluidity of the red blood cell membrane decreases as pH changes from 8 to 7.5. In rat liver mitochondrial (RLM) membrane fluidity precipitously declines as pH drops from 7.35 toward 7.0. With dithionitrobenzoate (Nbs2), reaction rates of mitochondrial -SH groups from rat liver and heart (RHM) and in beef heart submitochondrial particles are reduced at pH 7.0 as compared to 7.35. Similar results are obtained with the lipophilic fluorescence dye monobromobimane (MB). Bromobimane Q (MQ), which predominantly labels superficially located -SH groups, does not detect differences in -SH reaction rate between pH 7.35 and 7.0. Oligomycin diminishes the amount of reactive -SH groups in RLM titrated with Nbs2 only at pH 7.35, whereas with MB a decrease caused by oligomycin is found at pH 7.35 and pH 7.0. With MQ, an increase in reaction rate is observed for both pH values after pretreatment with oligomycin. Using 4-maleimido-TEMPO mobilization of -SH groups is found with oligomycin at pH 7.0, whereas at pH 7.35 they are immobilized. Phosphate significantly stimulates reaction rates of -SH groups at pH 7.0 in RHM and RLM. In RHM inhibition of succinate oxidation by oxaloacetate as well as the efflux of NAD(P)H is enhanced at pH 7.0, indicating increased permeability in both directions. Decreases in pH, fluidity, and thiol reactivity are important factors in hypoxic/ischemic membrane damage.

Animals↗
PubMed1990

Anti-human immunodeficiency virus (HIV) drug HOE/BAY946 increases membrane hydrophobicity of human lymphocytes and specifically suppresses HIV-protein synthesis.

The polysulfated polyxylan HOE/BAY946, which has been tested in two pilot studies in ARC/AIDS patients and in asymptomatic HIV carries in Germany, was believed to act by inhibiting virus attachment to the cell. However, the drug was also found to reduce the amount of HIV particles released from infected peripheral blood mononuclear cells (PBMC) in vitro. Furthermore, preincubation of PBMC with the drug led to a partial inhibition of a following HIV infection, suggesting that the drug also affects virus entry. Electron Paramagnetic Resonance (EPR) measurements on uninfected human lymphocytes using 5-proxyl-nonane as spin label demonstrated smaller hyperfine coupling constant (aN) values in the presence of HOE/BAY946 or dextran sulfate 5000. Accordingly, h-1p/h-1H ratios were decreased, indicating increased plasma membrane hydrophobicity and a membrane-stabilizing effect of the drugs. Culture of the chronically HIV-infected monocytic cell line U937/HIV-2D194 in the presence of HOE/BAY946 specifically and drastically reduced the release of virions and the intracellular synthesis of viral proteins as determined by radioimmunoprecipitation and reverse transcriptase assays. In conclusion, although the EPR studies showed a physico-chemical effect on membrane polarity, HOE/BAY946 and dextran sulfate clearly affect processes beyond the cell membrane. Thus, in contrast to previous reports suggesting that polysulfated sugars affect HIV only by inhibiting virus binding to uninfected cells, they clearly inhibit HIV in infected cells as well and appear to have a pleiotropic mode of action. Such drugs may be less likely to result in viral resistance after prolonged application than substances acting only on one step in the life cycle of the virus.

Antiviral Agents↗
PubMed1990

Multifunctional analysis of the interaction of anthralin and its metabolites anthraquinone and anthralin dimer with the inner mitochondrial membrane.

We studied the interaction of the antipsoriatic compound anthralin (1.8-dihydroxy-9-anthrone), and its metabolites anthraquinone (1.8-dihydroxy-9.10-anthraquinone) and anthralin dimer (1.8.1'.8'.-tetrahydroxy-10.10'-bis-9[10]-dianthrone) with the inner mitochondrial membrane. Mitochondrial membrane functions such as ubiquinone redox equilibria, redox status of iron sulfur clusters, cyanide-sensitive and cyanide-insensitive oxygen consumption, adenosine triphosphate (ATP) synthesis, ATP hydrolysis, and adenine nucleotide content of mitochondria were analyzed. Anthralin is an inhibitor of mitochondrial oxygen uptake in the presence of ADP and substrate (cyanide-sensitive respiration), inhibits ATP synthesis without affecting ATP hydrolysis, and depletes mitochondria of ATP. Anthralin dimer is a much weaker inhibitor of mitochondrial functions and anthraquinone is almost inactive. Anthralin, but not anthraquinone and anthralin dimer, reverses uncoupler stimulated oxygen consumption, stimulates cyanide-insensitive respiration, reduces mitochondrial ubiquinone-9 and -10 to the corresponding ubiquinols and reduces mitochondrial iron sulfur clusters. Anthralin may induce formation of reactive oxygen species by enhancing autoxidation of mitochondrial components and/or by catalyzed oxidation of anthralin. Taken together, anthralin acts as an electron donor to inner mitochondrial membrane associated redox components, inhibits the electron transport chain, and has an oligomycin-like effect. Anthralin dimer and anthraquinone do not function as electron donors and act by a different reaction mechanism. Respiratory measurements in human keratinocytes revealed similar results as obtained with isolated mitochondria. We suggest that modulation of membrane redox status may be a common concept of anthralin action in target cells such as keratinocytes and neutrophils.

Adenine Nucleotides↗
PubMed1990

Lyme carditis in immunodeficient mice during experimental infection of Borrelia burgdorferi.

Recently, we described the severe combined immunodeficiency (scid) mouse as a laboratory model for B. burgdorferi infection. Scid mice inoculated with the virulent low-passage tick isolate Borrelia burgdorferi ZS7 developed a severe pancarditis involving endocardium, myocardium and epicardium in the absence of functional B- or T-cells. Soon after inoculation perivascular infiltration was observed, later diffuse infiltration of the interstitium of the subendocardial and subepicardial areas was seen. The infiltrate was mainly mononuclear and predominantly composed of Mac-1+ cells. Concomitantly, fibroblast proliferation and augmented collagen deposition occurred in the interstitium. This was associated with the presence of B. burgdorferi organisms. The histopathological and ultrastructural findings observed in scid mice resemble those observed in human Lyme carditis. The data emphasize the suitability of the scid mouse as a model in which to study the role of the immune system in the pathogenesis of Lyme carditis.

Animals↗
PubMed1990

Human glomerular mesangial cells inactivate leukotriene B4 by reduction into dihydro-leukotriene B4 metabolites.

Due to its potent chemotactic properties leukotriene B4 is an important mediator of inflammatory reactions. Cultured human kidney mesangial cells converted exogenously added leukotriene B4 efficiently into three different more lipophilic metabolites, two of them probably representing dihydro-leukotriene B4 isomers. This represents an alternative metabolic pathway, in contrast to leukotriene B4 omega-oxidation found in human polymorphonuclear leukocytes. Both dihydro-leukotriene B4 isomers had nearly completely lost their ability to induce leukocyte chemotaxis as compared to leukotriene B4.

Cells, Cultured↗
PubMed1990

Clinical evaluation of hypothermic ventricular fibrillation, multi-dose blood cardioplegia, and single-dose Bretschneider cardioplegia in coronary surgery.

37 patients undergoing coronary revascularization were randomly assigned to three protocols for intraoperative myocardial protection: hypothermic ventricular fibrillation (HF) (n = 13), multi-dose blood cardioplegia (BCP) (n = 12) and single-dose Bretschneider's crystalloid cardioplegia (CCP) (n = 12). As intraoperative markers of ischemic damage myocardial ultrastructure, ATP, and CP contents were determined in left ventricular biopsy specimens taken before and after cardiac arrest. Release of serum enzymes (CK, CK-MB, LDH, SGOT) was determined pre- and postoperatively. Hemodynamic data were assessed before, during, and after operation. The incidence of low cardiac output, positive inotropic support, intraaortic balloon counterpulsation, peri-operative myocardial infarction, rhythm disturbances, and the rate of spontaneous defibrillation was compared between groups. The results show a better preservation of high energy phosphates in the BCP group as compared to the HF and CCP groups. Myocardial ultrastructure showed moderate ischemic damage in the hypothermic fibrillation group; in contrast, only slightly deteriorated cells were seen after cardiac arrest, when cardioplegia was used. The incidence of rhythm disturbances was 25% for HF and 42% for CCP. In contrast, only 17% of new rhythm disturbances were seen in the BCP group. Functional recovery (i.e. CI and SWI) of hearts protected with BCP was generally greater as compared to HF and CCP. Release of MB-creatine-kinase isoenzyme was higher in the HF group as compared to cardioplegia. Clinical outcome in terms of incidence of peri-operative infarction, positive inotropic support and low cardiac output was superior in the BCP group but not significantly different between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardioplegic Solutions↗
PubMed1990

[Flumazenil (Anexate): an antagonist of benzodiazepines. Its pharmacopsychologic significance and role in traffic medicine].

Flumazenil (Anexate) reverses promptly the hypnotic effects of all known benzodiazepines. From the point of view of traffic medicine the question is of interest whether side effects after application of flumazenil can be seen and must be taken in account. Our investigations were concerned in answering this question. 20 mg flumazenil or placebo was administered in a randomized doubleblind crossover fashion. The following psychometric tests were employed: Befindlichkeitsskalen von Zersen (Bf-S), State-Trait-Inventory (STAI), Hamilton Anxiety Scale (HAMA) und visual analogue scales (VAS). In addition, subjective condition was inquired. Pharmacokinetics were investigated by a radio-receptor-assay. Flumazenil leads to an increase of negative sensations in respect to an invers agonizing effect. Lack of concentration and dizziness were reported by the probationer.

Adult↗
PubMed1990

[Borrelia burgdorferi infection. I. Aspects of basic research, current approach for diagnosis and therapy].

In this review article the current concepts on the infection caused by Borrelia burgdorferi are presented. The problems associated with the diagnosis and therapy of the Borrelia burgdorferi infection are pointed out. A series of monoclonal antibodies recognizing Borrelia burgdorferi-associated antigens is presented. In collaborative research projects these antibodies were used for molecular biological (cloning and sequencing of Borrelia burgdorferi antigens) and immunological (protection experiments by passive transfer of monoclonal antibodies in an animal model) experiments. Taken together, these studies disclosed new aspects of the diagnosis and therapy of Borrelia burgdorferi infection. In the first part of the review article the immunochemical characterization of the aforementioned antibodies and their use for antigen detection by immunohistochemistry is described.

Algorithms↗
PubMed1990

Interferon-alpha and synthetic peptide malaria sporozoite vaccine in non-immune adults: antibody response after 40 weeks.

Adults with no known immunity to sporozoites received, i.m., at weeks 0 and 8 two single 200 micrograms doses of a peptide Plasmodium falciparum sporozoite vaccine conjugated to tetanus toxoid ((NANP)3-TT) plus placebo (group 1) or interferon-alpha (IFN-alpha) (group 2) and were followed for antibody responses at weeks 4, 12 and 40. Peak antibody responses were observed at week 12. At week 40, a greater than or equal to 4-fold increase in antibody titre to sporozoites in IFA, or to (NANP)50 in ELISA was still detectable in 6 of 12 (50%) volunteers in group 1 and in 16 of 25 (64%) in group 2. Peak antibody titres in IFA and ELISA decreased with a rate of 0.8% and 0.5% per week, respectively.

Animals↗
PubMed1990

Lyme borreliosis in the severe combined immunodeficiency (scid) mouse manifests predominantly in the joints, heart, and liver.

The authors describe the histopathologic evolution of Lyme disease in severe combined immunodeficiency (scid) and normal C.B-17 and C57BL/6 mice inoculated with Borrelia burgdorferi. Starting on day 7 after inoculation, all scid mice infected subcutaneously in the tail with a low-passage European tick isolate of B. burgdorferi had clinical evidence of arthritis characterized by reddening and swelling of tibiotarsal joints. Later on, other joints, ie, metatarsal and ulnacarpal joints were also affected. The infection of scid mice resulted in a persistent spirochetemia and the development of a multisystem disease with chronic progressive inflammation of joints, heart, and liver. Major histopathologic alterations included 1) severe joint lesions, characterized by the presence of hyperplastic inflamed synovial lining cells associated with the erosion and destruction of cartilage and/or bone; 2) pancarditis with infiltrations of mononuclear cells in the endocardium, myocardium, and pericardium; and 3) hepatitis with mononuclear cell infiltrations confined to the portal field and central vein, granulomatous reactions, and eventually the development of liver fibrosis. In addition, smaller more confined lesions were found in kidneys, lung, brain, and striated muscle. The inflammatory infiltrates in the various organs were associated mostly with Mac-1+ cells, largely monocytes and macrophages, as well as some polymorphonuclear leukocytes, but not B and T lymphocytes. Infective spirochetes could be readily isolated from blood and joints and were found at the site of inoculum and the myocardium. In contrast, subcutaneous inoculation of normal C.B-17 or C57BL/6 mice with spirochetes in general did not result in clinical signs of arthritis. Only 10% to 20% of the C57BL/6 mice, but none of the C.B-17 mice, showed clinical evidence of oligoarthritis, which appeared not before day 36 after inoculation. In general, the infection of normal mice resulted in minimal lesions in various organs, and no spirochetes could be visualized or reisolated from their tissues. The data demonstrate that Lyme borreliosis may develop in mice in the absence of detectable specific B and T cells and thus suggest an immunologic control of the disease in this species. The scid mouse model therefore can be used to define the components of the immune system responsible for the suppression and/or the progression of the disease.

Acquired Immunodeficiency Syndrome↗
PubMed1990

[Morphometric studies of the lung in shock of various etiologies].

The early schocklung-syndrome was investigated by morphological and morphometrical methods in order to discriminate the influence of different etiological factors on shock. Survival times up to 11 days were included in the investigation. We compared lungs from polytrauma with and without lung contusion and lungs after hypovolemic shock due to sharp violence. Cases of immediate death after brain damage served as controls. Apart from well known parameters of the shocklung--interstitial edema with increase of lung weight, intravasal sticking of granulocytes etc.--lymphangiektasy proved to be a reliable parameter to differentiate the temporal and etiological development of shock.

Humans↗
PubMed1989

The severe combined immunodeficiency (scid) mouse. A laboratory model for the analysis of Lyme arthritis and carditis.

We report that the spirochete B. burgdorferi induces progressive polyarthritis and carditis in mice with severe combined immunodeficiency syndrome (scid) but not in normal C.B-17 mice. The onset and severity of the disease were dependent on (a) the viability; (b) the infectivity; and (c) the dose of inoculated B. burgdorferi organisms. Infective spirochetes were isolated from both blood and joints of inoculated scid mice. These findings suggest that B. burgdorferi-induced chronic arthritis and carditis in mice develops independently of lymphocyte function and makes the scid mouse an attractive laboratory model to study the role of the immune system in experimental Lyme Borreliosis.

Animals↗
PubMed1989

Enzyme release from chick myocytes during hypoxia and reoxygenation: dependence on pH.

On reoxygenation of ischemic or hypoxic hearts a sudden release of cytosolic enzymes coupled with hypercontraction and cell injury occurs, which has been termed the "oxygen paradox". We have attempted to imitate this phenomenon in cultured chick myocytes to try to find the cause of this sudden enzyme release. During 4 hours of normoxic perfusion (pH 7.4) monolayer cultures of chick embryonic myocytes retain their normal morphology, beat rhythmically, and show no release of creatine kinase (CK) into the perfusate. Hypoxic perfusion (O2 less than or equal to 0.25 microliter/ml) stops cell contraction (15-20 min) and causes "blebbing" of the sarcolemma (20-30 min). Membrane blebs increase in size and number with continuing hypoxia and eventually the cells become irreversibly damaged. Perfusion at pH 7.4 leads to a release of CK shortly after membrane damage occurs (30-40 min), with peak enzyme levels at 60-90 min. Reoxygenation after 120 min hypoxia does not exacerbate release. Hypoxic perfusion at pH 7.0 suppresses the release of CK from the cells despite extensive membrane blebbing. Normoxic perfusion at pH 7.4 after 100 min hypoxia (pH 7.0) causes an efflux of enzyme from the irreversibly injured cells. This can be prevented by reoxygenating the cells at pH 7.0 and stimulated by raising the pH of the hypoxic perfusate to 7.4. Shorter hypoxic periods (30 mins) at pH 7.0 followed by normoxic perfusion at pH 7.4 lead to a sudden large efflux of CK, arrhythmic contractions and hypercontraction of myofilaments, i.e. the typical symptoms of the "oxygen paradox". Thus changes in external pH can influence the release of intracellular enzymes during hypoxia and reoxygenation.

Animals↗
PubMed1989

Myocardial protection by 2-mercaptopropionylglycine during global ischemia in dogs.

The hypothesis was tested, if the addition of 2-mercaptopropionylglycine (MPG, Thiola) to a crystalloid cardioplegic solution provides superior myocardial protection as assessed by biochemical and morphological parameters. Five mongrel dogs underwent a 60-min hypothermic cardioplegic arrest (untreated group). In six dogs, MPG (1.5 mmol/l) was added to the crystalloid cardioplegic solution (treated group). Thereafter a reperfusion phase of 60 min was established. At the end of the reperfusion phase samples for mitochondrial respiration parameters and for mitochondrial energization were collected. Samples for ultrastructure and negative staining were taken at the end of ischemia, and after 15, 30 and 60 min of reperfusion. Hearts which were treated with the MPG-enriched cardioplegic solution showed a better ultrastructure (1 (1/1) vs 2 (2/2), p less than 0.001) and superior preservation of the mitochondrial ATPases (2.4 +/- 2.0 versus 8.4 +/- 2.7, p less than 0.05) as compared to the untreated group at the end of ischemia. At the end of reperfusion, mitochondrial respiration, and energization of the mitochondria was improved significantly with the addition of MPG as compared to the untreated group.

Adenosine Triphosphatases↗
PubMed1989

Influences of tromantadine and nonoxinol 9 on the stability of red cell membrane.

The antiviral compound tromantadine (ViruMerz) and the detergent nonoxinol 9 have been investigated in their effects on biophysical parameters of red cell membranes. Up to a maximum ratio of 1 mol per 800 mol of phospholipids tromantadine enhances the membrane phase transition/separation break at 16-20 degrees C measured by 1-anilinonaphthalene-sulfonate (ANS) fluorescence. It also increases order parameters obtained from spin labeling experiments with 5-doxyl stearic acid. Nonoxinol 9 interacts with the membrane at a maximum ratio of 1 mol per 40 mol of phospholipids determined by UV spectrophotometry. The substance decreases the intensity of the above phase transition/separation break and the order parameters of the spin label 5-doxyl stearic acid. These experiments indicate that tromantadine probably stabilizes the membrane whereas nonoxynol 9 exhibits opposite effects. Combination of both compounds equalizes the influences of the single substances on the above biophysical parameters of red cell membrane with predominance of the nonoxinol 9 effect.

Amantadine↗
PubMed1989

[Report of 2 cases of isolated, primary amyloidosis of the male urethra and urinary bladder of a female].

Primary localized amyloidosis of the bladder and urethra is a rare condition. Two cases of isolated primary amyloidosis, of the urethra in a man and of the bladder in a woman, are reported. The clinical specificity of the location and the specific therapy are discussed. We draw attention to the extended, palette of diagnostic investigations now available and the new classification made possible by the introduction of immunohistochemistry and immunoelectron microscopy.

Aged↗