PubMed Health⌕ Search

Biomedical subjects

J Fuchs

Publications and source records attributed to J Fuchs.

At least 37 records · Page 2Linked to original sources
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

Effects of fish-oil ingestion on cardiovascular risk factors in hyperlipidemic subjects in Israel: a randomized, double-blind crossover study.

Effects of a daily fish-oil supplement on serum lipids, apolipoproteins, and some platelet functions and hemorheologic variables were examined in 27 hyperlipidemic subjects in a randomized, controlled, double-blind, crossover fashion with an identically encapsulated vegetable oil serving as the control treatment. Despite the habitual high linoleic acid intake of the study population, significant incorporation of n-3 (omega-3) fatty acids into the serum, platelet, and erythrocyte lipids was observed after the fish-oil supplement. Ingestion of fish oil resulted in a 40% decrease in the triglyceride concentration, a 12% increase in HDL cholesterol, and a significant decrease in plasma viscosity, whereas the vegetable-oil placebo had no significant effect. We conclude that a moderate intake of fish oil (15 g/d) is a feasible treatment for hypertriglyceridemia even in patients with a background of high linoleic acid intake and that it may have a beneficial effect on several cardiovascular risk factors.

Apolipoproteins↗
PubMed1990

Plasma viscosity, fibrinogen and haematocrit in the course of unstable angina.

Plasma viscosity, fibrinogen and haematocrit were measured in 80 patients with unstable angina on the 1st, 2nd and 5th day of hospitalization. In the group of patients who developed acute myocardial infarction (AMI) during hospitalization (20 patients), plasma viscosity was elevated during the entire observation period (1.69 +/- 0.05 cp, normal range 1.38-1.48 cp), while in patients who did not develop AMI, plasma viscosity was only mildly elevated (1.59 +/- 0.05 cp, P less than 0.001 vs the group who developed AMI) and tended to normalize towards the 5th day of hospitalization. Fibrinogen and haematocrit showed similar variations between the two groups. In a group of 20 patients who received heparin, the studied parameters were similar to the group who did not develop AMI. The importance of haemorheological factors in the clinical course of unstable angina is thus emphasized.

Adult↗
PubMed1990

The antipsoriatic compound anthralin influences bioenergetic parameters and redox properties of energy transducing membranes.

Bioenergetic parameters and redox properties of energy transducing membranes in rat liver mitochondria and cyanobacteria were investigated in the presence of the antipsoriatic compound anthralin (1,8-dihydroxy-9-anthrone). Transmembrane pH and electrical gradients were determined using electron paramagnetic resonance spectroscopy. In mitochondria, ubiquinones 9,10 and other redox components of the electron transport chain are reduced by anthralin; the proton motive force is increased. In the absence of ADP, anthralin slightly stimulates mitochondrial cyanide-insensitive oxygen consumption. It is suggested that increased cyanide-insensitive respiration is due to enhanced autoxidation of mitochondrial components and/or catalyzed oxidation of anthralin. In the presence of ADP mitochondrial respiration is decreased, and ATP synthesis is inhibited. Uncoupler-induced mitochondrial respiration is also decreased by anthralin, indicating inhibition of the electron transport chain. In the cyanobacterium Synechococcus PCC 6311 anthralin increases the pH gradient and decreases ATP levels. Thus, anthralin acts as an electron donor to membrane associated redox components and inhibits ATP synthesis in two different biologic systems. In human keratinocytes oxygen metabolism is influenced by anthralin in a similar pattern as in isolated mitochondria, and ATP content is decreased. Because anthralin reacts with redox components in different biologic membranes, alterations of subcellular/cellular redox status and energy metabolism might contribute significantly to its antiproliferative activity.

Animals↗
PubMed1990

Refraction in diabetics during metabolic dysregulation, acute or chronic. With special reference to the diabetic myopia concept.

The influence of diabetic dysregulation on refraction was analysed by a short-term and a long-term approach. a) Out of 15 patients admitted due to high blood sugars and followed over weeks, 11 showed refractive fluctuation of 1-6.5 D, in either direction-often with excess hypermetropia, while 4 appeared refractively stable. In those with refractive change a transient increase of lens thickness was suggested from ultrasound measurements. b) Diabetes control was evaluated retrospectively in 74 adult diabetics, mainly based on repeated 24 h urine glucose determinations over a 6-year period. As a group, those with low myopia did not score worse than those who had stayed emmetropic. Among the myopes, diabetes duration was longer in the subgroup where diabetes preceded myopia onset. - All considered, we found no support for dysregulation per se as an underlying factor behind the 'diabetic myopia' previously reported from our clinic.

Acute Disease↗
PubMed1990

pKa values and partition coefficients of nitroxide spin probes for membrane bioenergetics measurements.

Knowledge of pKa's is necessary to calculate intracellular/intravesicular pH values from nitroxide accumulation in cells or vesicles as detected with electron spin resonance (ESR) spectroscopy. pKa values were confirmed in lipid vesicles of known internal pH. To help select probes that do not accumulate in lipid membranes, octanol/buffer partition coefficients of uncharged nitroxides were determined. As an application of selected probes, pH gradients and internal aqueous volumes were analyzed in mitochondria (one internal compartment) and in the cyanobacterium Synechococcus 6311 (two internal compartments). The combination of 3-carboxy-, 3-amino- and 3-aminocarbonyl-2,2,5,5-tetramethylpyrrolidin-1-yloxyl was found to be most satisfactory for determinations of internal pH and volumes.

Animals↗
PubMed1990

Electron paramagnetic resonance in dermatologic research with particular reference to photodermatology.

The study of electron paramagnetic resonance (EPR) spectra in isolated skin cells, skin biopsies and the intact skin is the most direct approach to determining the existence, role and importance of ultraviolet-mediated generation of free radicals and other reactive oxygen species in dermatopathological processes. By means of spin labeling, the physicochemical properties of skin, such as membrane fluidity and polarity, can be analyzed. Spin probes can also be employed in measuring one-electron transfer reactions, and oxygen concentration in skin. EPR imaging is an emerging new technique and can be used to investigate the spatial distribution of all these parameters. The more widespread application of the EPR method in photodermatologic research will significantly contribute to improve understanding of biologic free radical processes.

Electron Spin Resonance Spectroscopy↗
PubMed1990

Chylous ascites as a presenting sign of prostatic adenocarcinoma.

Chylous ascites is usually associated with either primary disorders of the lymphatic system or malignancies of the lymph nodes such as Hodgkin and non-Hodgkin lymphoma. We describe, however, a young man in whom chylous ascites was a presenting sign of disseminated adenocarcinoma of the prostate gland. Most likely retroperitoneal lymph nodal replacement and tumor blockade of lymphatic collectors by metastatic adenocarcinoma was responsible for the development of chylous ascites.

Adenocarcinoma↗
PubMed1990

Distribution and plasticity of immunocytochemically localized GABAA receptors in adult monkey visual cortex.

Immunocytochemical methods were used to reveal new details of the distribution and plasticity of GABAA receptors in the visual cortex of adult monkeys; the findings were compared with those of autoradiographic experiments involving the binding of 3H-muscimol and 3H-flunitrazepam. In both areas 17 and 18, a monoclonal antibody to the purified GABAA complex (deBlas et al., 1988) produced staining of punctate profiles in the neuropil and around cell bodies and large processes in layers I-VI. The receptor immunostaining was relatively intense in layers II-III, IVA, IVC beta, and VI; these alternated with lightly stained layers I, IVB, IVC alpha, and V. In area 18, the laminar pattern was similar except that layer IV was split into a superficial, lightly stained half and a deep, intensely stained half. In sections cut parallel to the pial surface, receptor distribution in most layers was found to be uniform. There were 3 exceptions in area 17: (1) patches of intense receptor staining were present in layers II and III; (2) a widely spaced, irregular lattice of intense staining was found in layer IVA; and (3) a much finer, regular lattice was present in layer IVC. The patches in layers II-III and the lattice in layer IVA coincided precisely with regions of intense cytochrome oxidase (CO) staining. The binding of 3H-muscimol and 3H-flunitrazepam revealed a laminar pattern that was similar in most respects, including greater ligand binding in layer IVA of area 17, but showed no evidence of the sublaminar organization in layers IVA and IVC beta. Inhomogeneities in receptor immunostaining but not ligand binding were also seen in layer III of area 18. Following a 5 or 10 d period in which intravitreal injections of TTX had silenced ganglion cell activity in one retina, GABAA receptor immunostaining in layer IVC beta was distributed in intensely stained stripes, 450-550 microns wide, that alternated with narrower, lightly stained stripes. Stripes were also seen with receptor immunostaining and with the binding of the 2 radioligands in layer IVC beta of monocularly enucleated monkeys. Comparison with CO staining revealed that the stripes of reduced immunostaining or ligand binding corresponded to columns dominated by the TTX-injected or enucleated eye. Quantitatively, the binding in the deprived eye columns was reduced by 25%.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Lobomycosis (keloidal blastomycosis): case reports and overview.

Lobomycosis is a deep fungal disease of the skin without involvement of internal organs or mucous membranes. The disease is characterized by skin nodules and plaques resembling keloid involving the earlobes, distal parts of the upper and lower extremities, and buttocks. In severe cases, large skin areas can be covered by disseminated or grouped and confluent nodules. Most cases are reported from South and Central America. The fungus Paracoccidioides (Glenosporella) loboi is abundant in lesions but is extremely difficult to culture. Lobomycosis is resistant to chemotherapy, but in some cases it can successfully be treated by excision. Although the diagnosis is easily established by its typical clinical, histologic, and microbiological features, it is often misdiagnosed by physicians not familiar with the disease. We describe here five patients and present an overview of this rare disease.

Adult↗
PubMed1990

A method for the determination of circulating aggregated platelets and its application to patients in the course of unstable angina.

A method for the quantitative and qualitative determination of the number of aggregated platelets is described. One milliliter of venous blood was separated equally into two solutions. One solution composed of EDTA (ethylenediaminetetraacetic acid) and formaldehyde (solution F) contained reversibly and irreversibly aggregated platelets, and the second solution, composed of EDTA alone (solution E), contained irreversibly aggregated platelets. By microscopic readings, the percentage of platelets forming aggregates was determined. Reversibly aggregated platelets were estimated by subtracting the percentage of aggregated platelets in solution E from that in solution F. The average amount of platelets per aggregate was calculated by dividing the number of aggregated platelets in solution F by the number of aggregates per 1000 platelets counted. The reference ranges (means +/- SDs) established in 100 healthy persons were 5.8% +/- 2.4% (1% to 9%) for solution F, 3.9% +/- 1.8% (0% to 7%) for solution E, and 2.2 +/- 0.18 (2.0 to 2.5) for the average number of platelets per aggregate. Twenty hospitalized patients without heart disease had values similar to those of 100 normal subjects. In 50 patients with acute myocardial infarction, the percentage of aggregated platelets in solution F was 23.8% +/- 10.3%; in solution E, 4.0% +/- 3.0%; and the average number of platelets per aggregate, 2.9 +/- 0.7. The mean variance for five daily consecutive measurements was 0.52% for solution F, 0.63% for solution E, and 0.002 for the average number of platelets per aggregate. An even lesser mean variance was observed when the interobserver-vs-intraobserver and the intersmear-vs-intrasmear variations were tested. In patients with acute myocardial infarction, the interobserver-vs-intraobserver variance was 5.6% for solution F, 2.2% for solution E, and 0.005 for the average number of platelets per aggregate. The parameters studied were unaffected by different blood drawings, assay tubes, or venous stasis. In 80 patients with unstable angina, the studied parameters as well as the percentage of "big" platelets were measured on hospital days 1, 2, and 5. In 25 patients in whom acute myocardial infarction developed during hospitalization, the percentage of aggregated platelets was 28.1% +/- 8.3%. Most of them (71%) were reversibly aggregated and did not change during hospitalization. The average number of platelets per aggregate was 3.9 +/- 1.6, and the percentage of big platelets was 12.5% +/- 7.2%, both values not undergoing subsequent changes. In patients in whom acute myocardial infarction did not develop, the percentage of aggregated platelets decreased to 14.2% +/- 6.1% on day 5. Most aggregated platelets (58.8% to 90%) were irreversibly aggregated.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗