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Biomedical subjects

R Fuchs

Publications and source records attributed to R Fuchs.

At least 37 records · Page 2Linked to original sources
PubMed1991

Some pathomorphological features of Balkan endemic nephropathy in Croatia.

Over the last 16 years, 214 autopsies were done at the Department of Pathology and Forensic Medicine, Slavonski Brod Medical Centre, on people from an area recognized as endemic for Balkan nephropathy in the county. Balkan endemic nephropathy was diagnosed pathoanatomically and histopathologically in 94 of these cases, and in none of 1040 autopsies on people from a nonendemic area. The most striking pathological finding in all advanced cases of the disease was a marked reduction in kidney size and weight; in one extreme case, the organ weighed only 20 g. The process is invariably bilateral, but there are considerable differences in the degree of involvement in each pair. Although the pathoanatomical changes, including lung oedema and haemorrhage and fibrinous pericarditis, are seen in the majority of cases, they are not considered to be specific for Balkan endemic nephropathy, since they are well recognized signs of long-standing primary uraemia. The relevance of the peculiar finding of sulfurous yellow discoloration and hardened subcutaneous adipose tissue, seen frequently post mortem, is unknown and should be investigated in more detail. Histopathologically, fibrosis and atrophy of kidney cortex, with tubular degeneration, are the most consistent findings. Lesions characteristic of pyelonephritis were superimposed over the picture of 'pure' Balkan endemic nephropathy in a considerable number of cases.

Adipose Tissue↗
PubMed1991

Haematological features of the population of the area of Croatia, Yugoslavia, endemic for Balkan nephropathy.

Normochromic, normocytic anaemia is a sign recognized as essential for the diagnosis of Balkan endemic nephropathy, although its relationship to the disease is still unclear. The aim of this study was to investigate whether a random sample of the population of a village endemic for nephropathy differed from the population of a village with no clinical case of nephropathy with respect to certain basic haematological parameters. During a screening campaign in 1984, 133 blood samples were collected from the endemic village and 40 from the nonendemic village and analysed for a number of haematological parameters; in 1991, 449 samples were collected in the endemic village and 156 in the nonendemic village and analysed for haemoglobin content and red blood cell count. Whereas in 1984 the haemoglobin content and red blood cell count were significantly lower in the endemic village (p less than 0.01), in 1991 the erythrocyte count was much lower in the nonendemic village and there was no difference in haemoglobin concentration. Several controversial explanations, all of them speculative, are offered.

Anemia↗
PubMed1991

Measurement of tibial torsion and thigh-foot angle using goniometry and computed tomography.

Three therapists measured tibiofibular torsion and thigh-foot angle (TFA) goniometrically in 17 normal subjects, aged three to 24 years. Tibiofibular torsion was also measured using computed tomography (CT). Differences between testers for the goniometric measures were analyzed using a nonparametric analysis of variance. Wilcoxon's rank sum test was used to determine differences between goniometric and CT measures for tibiofibular torsion. No significant difference for goniometric measures was found between testers for tibiofibular torsion or TFA. A significant difference averaging 5 degrees between goniometric and CT torsion measures was found between testers. Although a significant difference was found between the two measurement methods, the degree of difference may not represent a significant clinical difference, as a range at 5 degrees is commonly reported as the margin of error for goniometric measurements.

Adolescent↗
PubMed1990

New services of the EMBL Data Library.

The existing services of the EMBL Data Library for external users have been improved and extended in several ways. The EMBL File Server has been reorganised, and many new databases and other information relevant to biologists are now accessible via global computer networks. A broad range of software for molecular biology is freely available for different popular computer systems, including the EMBL enhancements to the Wisconsin (GCG) Package. The new Mail-Quicksearch and Mail-FastA services give access to the latest sequence data for database searches by ordinary electronic mail.

Animals↗
PubMed1990

Purification of the Borrelia burgdorferi flagellum by use of a monoclonal antibody.

The flagellum associated polypeptide p41 is an immunodominant antigen of Borrelia burgdorferi in the early and late stages of Lyme borreliosis. p41 was prepared by affinity chromatography using monoclonal antibody specific for p41. An immunoglobulin class specific ELISA (IgM-, IgG-ELISA) was established with purified p41 as antigen and compared to the conventional ELISA with whole cell ultrasonic antigen. Whereas the sensitivity of IgM- and IgG-ELISA was comparable in both antigen preparations, crossreactivity of sera from syphilitic patients was reduced in the p41 IgG-ELISA. Discrepant results obtained by use of ultrasonic antigen or p41 antigen, were controlled by Western blots. A correlation between the results of p41-ELISA and Western blot was shown.

Antibodies, Monoclonal↗
PubMed1990

Free molecular biological software available from the EMBL file server.

A new service provided by EMBL (EMBL Software File Server) is described that will make free molecular biology software available to anyone with computer network access. MS-DOS, Apple Macintosh and VAX/VMX are supported at the moment. The programs will be delivered by normal electronic mail; conversion mechanisms will transform binary files to ASCII to allow mail transfer. This service will also help authors to distribute their software conveniently.

Computer Communication Networks↗
PubMed1990

[Differential ultrasound diagnosis of the healthy, inflamed and diseased gallbladder].

Sonography is helpful in detection of gallstones and can also provide information on pathological changes of the gallbladder. The diagnosis of changes of gallbladder walls is difficult without clinical symptoms. "Pharmakocholocystosonography" can provide information by diseases of gallbladder. It proves that the "asymptomatic" gallstone is one of symptoms of this disease. The sonography is helpful too in the diagnosis of the acute cholecystitis if the clinical symptoms are respected.

Acute Disease↗
PubMed1990

[The content of Hb and the hematocrit value in blood and the total proteins, urea, glucose, free fatty acids, Na, K, Ca, Mg, Pa, Fe, Fe-binding capacity, Cu and Zn in the blood plasma of Warmblood horses during feeding with oat-hay or barley-hay rations over a period of 9 months].

4 horses (Group A) received an oat-hay ration, through 9 months running, while 3 horses (Group B) were fed a barley-hay ration over the same period of time. Blood samples were collected and examined in 4-week intervals. All values considered, no differences were found to exist between the 2 groups with regard to Hb and haematocrit in blood as well as to protein, glucose, sodium, potassium, magnesium, iron fixation capacity, copper, and zinc in blood plasma. The urea level in plasma of Group A was higher than that in Group B, values being 5.76 +/- 0.64 mmol/l and 5.14 +/- 0.72 mmol/l. The same applied to free fatty acids, values being 150 +/- 83 mumols/l in Group A and 95 +/- 42 mumols/l in Group B. Calcium was 3.10 +/- 0.27 mmol/l in Group A and 2.92 +/- 0.26 mmol/l in Group B, while the A-B difference in inorganic phosphorus amounted to 1.62 +/- 0.65 against 1.99 +/- 0.77 mmol/l. Group A was inferior to Group B also with regard to iron in plasma, values being 28.6 +/- 2.42 mumols/l against 32.8 +/- 4.62 mumol/l. Causes underlying these differences are discussed in some detail.

Animal Feed↗
PubMed1989

Acidification and ion permeabilities of highly purified rat liver endosomes.

While it is well established that acidic pH in endosomes plays a critical role in mediating the orderly traffic of receptors and ligands during endocytosis, little is known about the bioenergetics or regulation of endosome acidification. Using highly enriched fractions of rat liver endosomes prepared by free flow electrophoresis and sucrose density gradient centrifugation, we have analyzed the mechanism of ATP-dependent acidification and ion permeability properties of the endosomal membrane. This procedure permitted the isolation of endosome fractions which were up to 200-fold enriched as indicated by the increased specific activity of ATP-dependent proton transport. Acidification was monitored using hepatocyte and total liver endosomes selectively labeled with pH-sensitive markers of receptor-mediated endocytosis (fluorescein isothiocyanate asialoorosomucoid) or fluid-phase endocytosis (fluorescein isothiocyanate-dextran). In addition, changes in membrane potential accompanying ATP-dependent acidification were directly measured using the voltage-sensitive fluorescent dye Di-S-C3(5). Our results indicate that ATP-dependent acidification of liver endosomes is electrogenic, with proton transport being accompanied by the generation of an interior-positive membrane potential opposing further acidification. The membrane potential can be dissipated by the influx of permeant external anions or efflux of internal alkali cations. Replacement externally of permeable anions with less permeable anions (e.g. replacing Cl- with gluconate) diminished acidification, as did replacement internally of a more permeant cation K+ with less permeant species (such as Na+ or tetramethylammonium). ATP-dependent H+ transport was not coupled to any specific anion or cation, however. The endosomal membrane was found to be extremely permeable to protons, with protons able to leak out almost as fast as they are pumped in. Thus, the internal pH of endosomes is likely to reflect a dynamic equilibrium of protons regulated by the intrinsic ion permeabilities of the endosomal membrane, in addition to the activity of an ATP-driven proton pump.

Animals↗
PubMed1989

Toxicokinetics of ochratoxin A in several species and its plasma-binding properties.

The toxicokinetic profile of ochratoxin A was studied after the oral or intravenous administration of 50 ng/g b.w. to fish, quail, mouse, rat and monkey. The elimination half-life varied from 0.68 h after oral administration to fish, up to 840 h after intravenous administration to monkey. The distribution volume ranged from 57 ml/kg in fish to 1500 ml/kg in quail. The plasma clearance was most rapid in quail and fish, 72 and 58 ml/kg.h, respectively, while it was only 0.17 ml/kg.h in monkey. The bioavailability was as low as 1.6% in fish but as high as 97% in mouse. The binding abilities of ochratoxin A to plasma proteins were also studied. From these data we calculated the free fraction of toxin in plasma, which we found to be less than 0.2% in all species investigated (including man) except fish. A similar but smaller investigation on the toxicokinetics and binding properties of ochratoxin B was also performed. Ochratoxin B was more readily eliminated and had a lower affinity for plasma proteins, which partly may explain its lower toxicity.

Administration, Oral↗
PubMed1989

Practical considerations in the production, purification, and formulation of monoclonal antibodies for immunoscintigraphy and immunotherapy.

Issues associated with the large-scale production of monoclonal antibodies for pharmaceutical applications are examined. The development of a commercial monoclonal antibody production process involves much more than just scaling-up the laboratory process and making it cost-effective. It involves establishing the hybridoma cell bank with cells that are free of adventitious agents such as viruses and mycoplasma, that have stability in continuous culture for antibody-production rate and cell viability, and that do not have unusual or expensive media requirements. The style and mode of operation of the bioreactor used to produce the antibody must be explored. The antibody-based product must be processed to high levels of purity, and specific contaminants such as DNA and endotoxin must be reduced to extremely low levels. Appropriate labeling or drug conjugation chemistries must also be developed. The product must be formulated so that it has performance characteristics that are stable over a reasonable period of time. Adequate test procedures must be developed to assure product purity, activity, stability, and safety on a lot-to-lot-basis. Compliance with federal regulations, guidelines, and procedures must be guaranteed. In the coming decade, it is likely that the two arms of biotechnology, hybridoma technology and recombinant DNA technology, will be used together to generate unique protein molecules. These new reagents will face the same practical considerations summarized in this review.

Animals↗
PubMed1989

A possible role for Na+,K+-ATPase in regulating ATP-dependent endosome acidification.

Endosomes maintain a slightly acidic internal pH, which is directly responsible for their ability to ensure proper sorting of incoming receptors and ligands during endocytosis. At least two distinct subpopulations of endosomes can be distinguished, designated "early" and "late" on the basis of their kinetics of labeling with endocytic tracers. The subpopulations differ not only in their functions (rapid receptor recycling and transport to lysosomes, respectively) but also in their capacities for acidification in intact cells and in vitro. To investigate the possible basis for pH regulation in endosomes, we have studied the transport properties and ion permeabilities of early and late endosomes isolated from Chinese hamster ovary cells. Using endosomes selectively labeled with pH-sensitive endocytic tracers, we found that ATP-dependent acidification is electrogenic, being accompanied by the generation of an interior-positive membrane potential which opposes further acidification. While membrane potential and, consequently, acidification was controlled by the influx of permeant anions and efflux of protons and alkali cations, acidification was further modulated in Na+ and K+-containing buffers by the ouabain- and vanadate-sensitive Na+,K+-ATPase, which appears to be a functional component of the endosomal membrane. The data suggest that electrogenic Na+ transport due to Na+,K+-ATPase activity contributes to the interior-positive membrane potential, thereby reducing ATP-dependent H+ transport. Importantly, inhibition of acidification by Na+,K+-ATPase activity was found only in early endosomes, consistent with their limited acidification capacity relative to late endosomes and lysosomes.

Animals↗
PubMed1989

Acidification of endosome subpopulations in wild-type Chinese hamster ovary cells and temperature-sensitive acidification-defective mutants.

During endocytosis in Chinese hamster ovary (CHO) cells, Semliki Forest virus (SFV) passes through two distinct subpopulations of endosomes before reaching lysosomes. One subpopulation, defined by cell fractionation using free flow electrophoresis as "early endosomes," constitutes the major site of membrane and receptor recycling; while "late endosomes," an electrophoretically distinct endosome subpopulation, are involved in the delivery of endosomal content to lysosomes. In this paper, the pH-sensitive conformational changes of the SFV E1 spike glycoprotein were used to study the acidification of these defined endosome subpopulations in intact wild-type and acidification-defective CHO cells. Different virus strains were used to measure the kinetics at which internalized SFV was delivered to endosomes of pH less than or equal to 6.2 (the pH at which wild-type E1 becomes resistant to trypsin digestion) vs. endosomes of pH less than or equal to 5.3 (the threshold pH for E1 of the SFV mutant fus-1). By correlating the kinetics of acquisition of E1 trypsin resistance with the transfer of SFV among distinct endosome subpopulations defined by cell fractionation, we found that after a brief residence in vesicles of relatively neutral pH, internalized virus encountered pH less than or equal to 6.2 in early endosomes with a t1/2 of 5 min. Although a fraction of the virus reached a pH of less than or equal to 5.3 in early endosomes, most fus-1 SFV did not exhibit the acid-induced conformational change until arrival in late endosomes (t1/2 = 8-10 min). Thus, acidification of both endosome subpopulations was heterogeneous. However, passage of SFV through a less acidic early endosome subpopulation always preceded arrival in the more acidic late endosome subpopulation. In mutant CHO cells with temperature-sensitive defects in endosome acidification in vitro, acidification of both early and late endosomes was found to be impaired at the restrictive temperature (41 degrees C). The acidification defect was also found to be partially penetrant at the permissive temperature, resulting in the inability of any early endosomes in these cells to attain pH less than or equal to 5.3. In vitro studies of endosomes isolated from mutant cells suggested that the acidification defect is most likely in the proton pump itself. In one mutant, this defect resulted in increased sensitivity of the electrogenic H+ pump to fluctuations in the endosomal membrane potential.

Animals↗
PubMed1989

Intratracheal exposure of rats to Aspergillus fumigatus spores isolated from sawmills in Sweden.

Five strains of Aspergillus fumigatus (A, B, D, H, and K) isolated from sawmills were used to expose groups of three rats by intratracheal intubation. The dose was 10(9) spores per rat. At 48 h after administration, two rats from the D group and all rats from the K group died with symptoms of strong dyspnea and tachypnea. At 72 h postadministration and after, some animals showed mild to moderate dyspnea and tachypnea. Autopsies of all animals were performed, including a histopathological examination of the lungs. At 72 h after administration, two distinct morphological groups were identified histopathologically. Severe necrotizing pneumonia characterized by the presence of abundant fungal hyphae was seen in animals that died spontaneously within 48 h postadministration and rats with bronchopneumonia and was characterized by the presence of numerous fungal spores. There was an obvious difference in pathogenicity among the strains of A. fumigatus. Strains D and K were more pathogenic, and only the rats exposed to these strains showed the presence of fungal hyphae in the lungs. The mycotoxin gliotoxin that is produced by A. fumigatus and has antiphagocytic activity was not detected in the spores from any of the A. fumigatus strains.

Animals↗