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Biomedical subjects

J Fuchs

Publications and source records attributed to J Fuchs.

At least 181 records · Page 10Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Escherichia coli thioredoxin folds into two compact forms of different stability to urea denaturation.

The urea-induced denaturation of Escherichia coli thioredoxin and thioredoxin variants has been examined by electrophoresis on urea gradient slab gels by the method of Creighton [Creighton, T. (1986) Methods Enzymol. 131, 156-172]. Thioredoxin has only two cysteine residues, and these form a redox-active disulfide at the active site. Oxidized thioredoxin-S2 and reduced thioredoxin-(SH)2 each show two folded isomers with a large difference in stability to urea denaturation. The difference in stability is greater for the isomers of oxidized than for the isomers of reduced thioredoxin. At 2 degrees C, the urea concentrations at the denaturation midpoint are approximately 8 and 4.3 M for the oxidized isomers and 4.8 and 3.7 M for the reduced isomers. The difference between the gel patterns of samples applied in native versus denaturing buffer, and at 2 and 25 degrees C, is characteristic for the involvement of a cis-proline-trans-proline isomerization. The data very strongly suggest that the two folded forms of different stabilities correspond to the cis and trans isomers of the highly conserved Pro 76 peptide bond, which is cis in the crystal structure of oxidized thioredoxin. Urea gel experiments with the mutant thioredoxin P76A, with alanine substituted for proline at position 76, corroborate this interpretation. The electrophoretic banding pattern diagnostic for an involvement of proline isomerization in urea denaturation is not observed for oxidized P76A. In broad estimates of delta G degree for the native-denatured transition, the difference in delta G degree (no urea) between the putative cis and trans isomers of the Ile 75-Pro 76 peptide bond is approximately 3 kcal/mol for oxidized thioredoxin and approximately 1.5 kcal/mol for reduced thioredoxin. Since cis oxidized thioredoxin is much more stable than trans, folded oxidized thioredoxin is essentially all cis. In folded reduced thioredoxin, cis and trans interconvert slowly, on the minute time scale at 2 and 25 degrees C. In the absence of urea, the folded reduced thioredoxin is less than a few percent trans. Three additional mutants with additions or substitutions at the active site also show electrophoresis banding patterns consistent with a difference in stability between cis and trans isomers.

Bacterial Proteins↗

Atrial fibrillation. Cause and time of onset.

To characterize groups of patients presenting at the emergency room with atrial fibrillation (AF) according to the various causes of AF and the time of its onset, 704 medical files from the Beilinson Medical Center (Petah Tikva, Israel), during an eight-year period, were reviewed. Two thirds of all patients converted to sinus rhythm (SR) within a seven-day in-hospital treatment. The most frequent causes associated with AF were atherosclerotic cardiovascular disease, 55%; rheumatic heart disease, 22.8%; chronic obstructive pulmonary disease, 2.8%; Wolf-Parkinson-White syndrome, 2.6%; and thyrotoxicosis, 2.6%. There was a relatively large group of idiopathic AF (4.5%). Best convertors to SR were patients with idiopathic AF (93.9%), then patients with Wolf-Parkinson-White syndrome (88.8%), followed by atherosclerotic cardiovascular disease (71.6%), and thyrotoxicosis (63.2%). Patients with rheumatic heart disease and chronic obstructive pulmonary disease had the lowest percentage of successful conversion to SR--46% and 55%, respectively. We conclude that there are differences regarding gender, age, and possible conversion of AF to SR according to the different causes of AF.

Aged↗

Drug-related syncope.

The records of 483 patients admitted to the emergency room because of syncope were reviewed. Forty-one patients were found to have drug-related syncope. Thirty-nine experienced syncope related to drugs administered for cardiovascular disease. The most frequently associated diseases were anginal syndrome (22 patients), hypertension (13 patients), and a history of myocardial infarction (6 patients). Thirty-eight patients experienced symptomatic orthostatic hypotension following drug taking (nitrates in 19 patients, beta blockers in 10 patients, nifedipine in 3 patients, prazosin and quinidine in 2 patients each, methyldopa and verapamil in 1 patient each). One patient developed complete heart block as a result of digoxin intoxication. Two patients developed the characteristic picture of anaphylactic reaction (1 with ampicillin, 1 with dipyrone). During one-year follow-up, without the offending medications, no further syncopal episodes were reported by these patients. We conclude that drug-related syncope was more common among our patients with syncope than had been reported previously. It is suggested that drug-related syncope should be taken into consideration in any patient with syncope who is treated by any of the above-mentioned drugs.

Adult↗

Does determination of serum aspartate aminotransferase contribute to the diagnosis of acute myocardial infarction?

Values for total lactate dehydrogenase (LD), LD isoenzymes, and serum aspartate aminotransferase (AST) were determined in 150 patients with acute myocardial infarction (AMI) and 130 non-AMI patients 24, 48, and 72 hours after admission. The authors assessed the diagnostic yield of a single determination of AST, LD, and three LD isoenzymes tests: LD-1 greater than LD-2; LD-1 greater than 90 U/L; LD-1/LD greater than 0.4. They also assessed the diagnostic accuracy of combined determination of AST with LD and AST with each of the above three LD isoenzymes tests. The efficiency of single determination of AST was better than that of LD (88% vs. 80%, 48 hours after admission). The most efficient single test for diagnosing AMI was the LD-1 greater than 90 U/L test (92%, 48 hours after admission). The efficiency of the combined AST/LD test was better than that of a single determination of each of the two enzymes (90% vs. 88% and 80%, 48 hours after admission). The highest efficiency was achieved, however, with combined determination of AST and any of the three LD isoenzymes tests. It was found to be more efficient than single determination of each of the LD isoenzymes tests (95.5-96% vs. 89-92.5%) and more efficient than the combined determination of the AST/LD test (95.5-96% vs. 89-90%). The authors conclude that AST should be determined in every patient with suspected AMI because its determination may contribute to the diagnostic yield of LD isoenzymes tests, especially in patients with AMI admitted 48-72 hours after onset of symptoms, when creatine kinase declined to near normal values.

Adult↗

Impairment of enzymic and nonenzymic antioxidants in skin by UVB irradiation.

Antioxidants may play a significant role in ameliorating or preventing photobiologic damage in skin that could lead to cutaneous disorders such as cancer and premature aging. The objective of this study was to assess the acute cutaneous enzymic and nonenzymic antioxidant response to a single exposure of large fluence (300 mJ/cm2) ultraviolet radiation (greater than 280 nm) in hairless mice. This treatment caused an immediate and statistically significant inhibition of glutathione reductase and catalase activity. Glutathione peroxidase and superoxide dismutase were not affected. Glutathione levels decreased and, conversely glutathione disulfide concentrations increased. A slight depletion of the total glutathione was observed, while the content of total ascorbic acid did not change. The lipophilic antioxidants alpha-tocopherol, ubiquinol 9 and ubiquinone 9 also decreased significantly, and the concentration of malondialdehyde remained constant. The free radical scavenging activity of epidermis, as assessed by reduction of the stable, cationic nitroxide radical [2,2,6,6-tetramethyl-1-piperidinoxy-4-(2',4',6'-trimethyl) methylpyridinium perchlorate] was considerably inhibited. The study indicates that immediately after exposure to a large fluence of ultraviolet radiation the enzymic and nonenzymic antioxidant capacity of skin decreases significantly.

Animals↗

Free radical reduction mechanisms in mouse epidermis skin homogenates.

Scavenging mechanisms for persistent free radicals were investigated using nitroxide-type radicals as model compounds. The free radical reducing activity of a) isolated thioredoxin reductase, a flavin containing oxidoreductase, b) skin homogenates, and c) the epidermis of hairless mice was studied by electron spin resonance spectroscopy. In all three systems, reduction rates of different classes of nitroxide free radicals exhibited the following order: oxazolidinoxy greater than piperidinoxy greater than dihydropyrroloxy. The main reductant for piperidinoxy radicals in mouse skin homogenate is ascorbic acid. Other reducing activities were stimulated by NAD(P)H and could be inhibited by N-ethyl maleimide, suggesting involvement of thiol-dependent processes. Mammalian thioredoxin, a competitive inhibitor of nitroxide reduction by thioredoxin reductase, significantly stimulates nitroxide scavenging in skin homogenate. Thioredoxin reductase did not significantly participate in nitroxide reduction in skin homogenates. At the surface of mouse epidermis a cationic dihydropyrroloxy nitroxide, which was stable in the presence of mammalian thioredoxin reductase was readily reduced. The epidermal reduction was inhibited by zinc, N-ethyl maleimide, and by heat (70 degrees C, 5 min). At least for mouse epidermis, reduction of a variety of nitroxides is a complex phenomenon involving enzymatic and nonenzymatic mechanisms and cannot be used as a specific assay for an enzyme, e.g., thioredoxin reductase. The study indicates the epidermis contains an effective antioxidant system that scavenges ascorbate-sensitive piperidinoxy nitroxides as well as more reducing radicals exemplified by dihydropyrroloxy nitroxides.

Animals↗

Investigations of anthralin free radicals in model systems and in skin of hairless mice.

The antipsoriatic compound anthralin (1.8-dihydroxy-9-anthrone) is converted in skin into several oxidized products, including persistent free radicals that are not well characterized. Anthralin oxidation was investigated by electron spin resonance spectroscopy in a biological system and in a chemical system. Free radical formation in the skin of hairless mice is reduced by the antioxidant tocopherol. The data indicate that tocopherol acts by interfering with free radical formation rather than by scavenging persistent anthralin radicals directly. The skin radicals do not correspond to 10-anthranyl, the initial paramagnetic anthralin oxidation product. Similar radicals obtained in skin are formed by anthralin exposed to ultraviolet light or alkaline solution and by mitochondria and microsomes. The pertinent skin radical is attributed to products derived from anthralin dark structures, the final oxidation products of anthralin. It is suggested that resonance stabilized, paramagnetic polycyclic hydrocarbons are the compounds detected. Their stability and low reactivity indicate a low potential for cutaneous irritation and tumor promotion. Reactive oxygen species, which have been reported to be formed concomitantly during oxidation of anthralin, and the initially formed highly reactive 10-anthranyl radical are more potent candidates for mediating tumor promotion and inflammation.

Animals↗