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Biomedical subjects

B Hoffmann

Publications and source records attributed to B Hoffmann.

At least 109 records · Page 6Linked to original sources

[Our first experiences with intermittent assisted ventilation in patients with amyotrophic lateral sclerosis].

Amyotrophic lateral sclerosis is one of the most frequent neuromuscular diseases in adults. Chronic respiratory failures is an almost compulsory symptom in the progression of this disease, and in association with pulmonary infections, responsible for the majority of deaths. We report on a series of 43 patients. An advanced stage of clinical disease was seen in half of them. After detection of respiratory failure corresponding to the guidelines of muscle centres of the DGM (Deutsche Gesellschaft für Muskelerkrankungen), seven patients (16.3%) were willing to be provided with a system for intermittent non-invasive ventilation. All patients achieved stabilisation of respiratory function, both with respect to the normalisation of arterial gases and subjective improvement of well-being. During the course of treatment four patients deliberately underwent permanent invasive ventilation. In our opinion home ventilation is a valid additional tool in the palliative treatment of amyotrophic lateral sclerosis. The treatment, however, must be supported by an interdisciplinary team.

Adult↗

Peripheral fields of sympathetic vasoconstrictor neurons in guinea pigs.

We have combined retrograde axonal tracing using Fast Blue and Dil, with immunohistochemistry, to estimate the maximum size of peripheral fields of identified sympathetic vasoconstrictor neurons projecting to guinea-pig ear tips. Many neurons in the superior cervical ganglia were labelled with both Fast Blue and Dil after dye injections up to 7 mm apart. Few neurons were labelled when dye injections were 8-10 mm apart. Neurons labelled with both Dil and Fast Blue after dye injections 5-7 mm apart had, on average, larger somata (436 +/- 84 microm2, mean +/- SEM, n = 47) than neurons labelled with Dil only (388 +/- 11 microm2, n = 147). Typically, 50-100 neurons innervated a region of vasculature 1 mm in diameter. We conclude that sympathetic vasoconstrictor neurons branch widely before converging on to their target blood vessels. Progressive recruitment of vasoconstrictor neurons with increasing field size would provide an efficient mechanism for graded neural control of the circulation.

Amidines↗

Monitoring the Gcn4 protein-mediated response in the yeast Saccharomyces cerevisiae.

In Saccharomyces cerevisiae the GCN4 gene encodes the transcriptional activator of the "general control" system of amino acid bioynthesis, a network of at least 12 different biosynthetic pathways. We characterized the consequences of the general control response upon the signal "amino acid starvation" induced by the histidine analogue 3-aminotriazole with respect to Gcn4p levels in more detail. Therefore, we established test systems to monitor the time course of different parameters, including GCN4 mRNA, Gcn4 protein, Gcn4p DNA binding activity, as well as Gcn4p transactivation ability. We observed a biphasic response of Gcn4p activity in the cell. At first, translation of GCN4 mRNA is induced within 20 min after switch to starvation conditions. However, an additional increase in GCN4 transcript steady state level was observed, leading to an additional second phase of GCN4 expression after 3-4 h of starvation. The DNA binding activity of Gcn4p, as well as the ability to activate transcription of target genes, correlate with the amount of Gcn4 protein in the cell, suggesting that under the tested conditions there is no additional regulation of DNA binding or transactivation ability of Gcn4p, respectively.

Amitrole↗

Characterization of plasmid regions of foodborne Yersinia enterocolitica biogroup 1A strains hybridizing to the Yersinia enterocolitica virulence plasmid.

The aim of our study was to find out if plasmids of foodborne Yersinia enterocolitica biogroup 1A strains harbour genes related to the virulence genes located on the virulence plasmid pYV of Yersinia enterocolitica. The foodborne strains were isolated from pork, as pigs are considered as an important reservoir for enteropathogenic Y. enterocolitica 0:3 and 0:9 strains. The plasmids of the foodborne strains were characterized by restriction enzyme analysis and hybridized to the virulence plasmid pYV of pathogenic Y. enterocolitica strains (0:3 biogroup 4; 0:9 biogroup 2). In several cases the plasmids of the foodborne strains showed homologies to parts of the pYV plasmid. Analysis of the hybridizing regions revealed that genes involved in replication, sequences of transposable elements and an endonuclease gene caused the observed hybridization to the virulence plasmid. In cause of the study also a remnant of a Tn3-like transposon was shown to be present adjacent to the yadA gene on the pYV plasmid. Although there is evidence that at least some strains of Y. enterocolitica biogroup 1A might possess pathogenic properties none of the well known plasmid encoded virulence genes were present on the plasmids of the investigated foodborne biogroup 1A strains.

Animals↗

Hymenobacter roseosalivarius gen. nov., sp. nov. from continental Antartica soils and sandstone: bacteria of the Cytophaga/Flavobacterium/Bacteroides line of phylogenetic descent.

Aseptically collected sandstone and soil samples from the antarctic Dry Valleys were inoculated into oligotrophic media and incubated under low light intensities. A total of 41 Gram-negative isolates were obtained with reddish colonies spreading on agar. A sandstone isolate and four soil strains were characterized further. They were nearly identical in morphological, physiological, biochemical and chemotaxonomic properties. They produced large amounts of extracellular polymer and utilized for growth: glucose, saccharose, mannitol, sorbitol, L-aspartate, malate and acetate, but not D-ribose, adonitol, DL-alanine, glutamate, glycolate, lactate or succinate. All strains hydrolyzed gelatin, starch, casein, xylan, Tweens 80 or 60 and dead or living yeast cells, but not cellulose or pectin. Nitrate was not reduced, ethanol was not oxidized and acid was not produced from maltose, mannitol or dulcitol. Ammonia was not produced from peptone. They were strictly aerobic. Major fatty acids were n 16:1 d 9, n 16:1 d 11, n 17:1 d 11, and i 15:0. The strains contained the quinone MK-7 and phosphatidylethanolamine as the main phospholipid. The base ratio ranged from 55 to 61 mol% G+C. A 16S rRNA sequence analysis of strains AA-688 and AA-718 showed these to be identical and to represent a special phylogenetic group within the Cytophaga/Flavobacterium/Bacteroides major line of descent. Three soil strains labeled "Taxeobacter" Txc1, Txg1, and Txo1 (Reichenbach, 1992) belonged to the same group but had lower sequence similarities (<95%). Some of their characteristics were different from those of the antarctic strains: the utilization of C-compounds, hydrolysis of polymers, temperature tolerances, major fatty acids and base ratios. Txc1 and Txg1 may later have to be considered as members of this group, possibly on the species level, while Txo1 could represent a different related genus. It is concluded that the five antarctic strains represent a new genus and species for which the name of Hymenobacter roseosalivarius is proposed. The type strain is AA-718T (DSM 11622T).

Antarctic Regions↗

Evaluation of filling materials in membrane--protected bone defects. A comparative histomorphometric study in the mandible of miniature pigs.

In recent years, bone grafts and bone substitutes have been increasingly utilized underneath barrier membranes to optimize the treatment outcome of bone reconstructive therapy for defects in the alveolar process. In the present study, 4 different filling materials were evaluated in bone defects of similar dimensions in the mandible of miniature pigs. Blood clots and autografts were used as controls. The defects were covered with barrier membranes and allowed to heal for 4, 12 or 24 weeks. Histologic examination demonstrated that bone repair progressed through a programmed sequence of maturation steps closely resembling the pattern of bone development and growth regardless of whether bone grafts or substitutes were present or not. Histomorphometric analysis showed that autologous bone grafts (autografts) had the best osteoconductive properties during the initial healing period, with 39% of newly formed bone inside the membrane-covered defects at 4 weeks of healing. In addition, 87% of the graft surfaces were already covered by bone at this time. Both values were significantly higher for autografts than for the 4 alternative bone fillers (P < or = 0.05). At 12 weeks, these differences were no longer apparent, with all 5 filling materials showing similar values. Among the tested bone substitutes, tricalcium phosphate (TCP) showed a significantly higher percentage of bone fill at 24 weeks of healing. It can be concluded that sites filled with autografts clearly demonstrated the best results underneath barrier membranes in the early phase of healing. As far as degradation and substitution are concerned, TCP showed the most promising results. This filler, however, needs to be tested further in a more demanding animal model. Less favorable results were obtained for coral-derived hydroxyapatite granules and for demineralized freeze-dried bone allografts.

Alveolar Bone Loss↗

Stepwise transformation of a cholera toxin and a p24 (HIV-1) epitope into D-peptide analogs.

We have transformed two peptide epitopes into D-peptide analogs: VPGSQHIDS derived from cholera toxin recognized by the antibody TE33, and GATPQDLNTML from the HIV-1 capsid protein p24 recognized by the antibody CB4-1. The transformation process was performed by stepwise substitution of each single epitope position by all 19 D-amino acids and glycine followed by antibody binding studies and selection of one D-analog for further transformation. Thus, each transformation step introduced one novel D-position into the peptide. For both epitopes complete D-analogs were obtained. The cholera toxin-derived variant dwGsqhydp binds to the antibody TE33 with higher affinity than its original epitope, whereas in the case of the p24-derived analog saGdwwGkssl lower affinity was detected. Both D-peptides are completely stable in serum for several days. Antibody interaction models for both D-molecules were generated by computer-assisted modelling based on the crystal structures of the starting complexes. Compared with the L-peptides, the binding conformation of dwGsqhydp is very similar, whereas saGdwwGkssl displays a completely different interaction mode.

Amino Acid Sequence↗

Search for life on Mars.

A multi-user integrated suite of instruments designed to optimize the search for evidence of life on Mars is described. The package includes: -Surface inspection and surface environment analysis to identify the potential Mars landing sites, to inspect the surface geology and mineralogy, to search for visible surficial microbial macrofossils, to study the surface radiation budget and surface oxidation processes, to search for niches for extant life. -Subsurface sample acquisition by core drilling -Analysis of surface and subsurface minerals and organics to characterize the surface mineralogy, to analyse the surface and subsurface oxidants, to analyse the mineralogy of subsurface aliquots, to analyse the organics present in the subsurface aliquots (elemental and molecular composition, isotopes, chirality). -Macroscopic and microscopic inspection of subsurface aliquots to search for life's indicators (paleontological, biological, mineralogical) and to characterize the mineralogy of the subsurface aliquots. The study is led by ESA Manned Spaceflight and Microgravity Directorate.

Europe↗

Leukodystrophy incidence in Germany.

Through a survey of all departments of pediatrics, neurology and neuropathology in Germany, we calculated the incidence of all major forms of leukodystrophy. Only diagnoses based on specific biochemical tests in association with typical findings and/or neuroradiologically proven white matter involvement were accepted. In accordance with these strict criteria, 617 cases of leukodystrophy were found (incidence of all forms: app. 2.0/100,000). Minimal incidence was estimated at 0.8/100,000 for adrenoleukodystrophy/adrenomyeloneuropathy (ALD/AMN), 0.6/100,000 for metachromatic leukodystrophy (MLD), and 0.6/100,000 for Krabbe disease. Thus ALD/AMN is apparently underdiagnosed in Germany. A considerable proportion of leukodystrophies could not be classified in spite of adequate diagnostic procedures in experienced centers.

Adolescent↗

Chloroplast import of four carotenoid biosynthetic enzymes in vitro reveals differential fates prior to membrane binding and oligomeric assembly.

The precursor proteins of the carotenogenic enzymes geranylgeranyl diphosphate synthase, phytoene synthase, phytoene desaturase and lycopene cyclase were imported into isolated pea chloroplasts. Geranylgeranyl diphosphate synthase remained soluble in the stroma in a free form and phytoene synthase associated to thylakoid membranes upon import, both as expected. Surprisingly, phytoene desaturase and lycopene cyclase, which strongly depend on membrane association for enzymatic activity, also remained soluble in the chloroplast stroma. The soluble forms of these enzymes were, however, still competent for membrane-association, e.g. with protein-free liposomal membranes. Indeed the soluble forms of phytoene synthase, phytoene desaturase and lycopene cyclase occurred as ATP- and cold-sensitive high-molecular-mass complexes. Gel-filtration experiments and blue native-PAGE plus autoradiography and western blot analysis indicated a participation of the chloroplast 60-kDa chaperonin (Cpn60) in the soluble high-molecular-mass complexes of imported carotenogenic enzymes. Finally, it was inferred that a membrane-bound regulatory factor plays a decisive role in membrane-binding.

Adenosine Triphosphate↗

Influence of gene dosage and autoregulation of the regulatory genes INO2 and INO4 on inositol/choline-repressible gene transcription in the yeast Saccharomyces cerevisiae.

Expression of structural genes of phospholipid biosynthesis in yeast is mediated by the inositol/choline-responsive element (ICRE). ICRE-dependent gene activation, requiring the regulatory genes INO2 and INO4, is repressed in the presence of the phospholipid precursors inositol and choline. INO2 and, to a less extent, INO4 are positively autoregulated by functional ICRE sequences in the respective upstream regions. However, an INO2 allele devoid of its ICRE functionally complemented an ino2 mutation and completely restored inositol/choline regulation of Ino2p-dependent reporter genes. Low-level expression of INO2 and INO4 genes, each under control of the heterologous MET25 promoter, did not alter the regulatory pattern of target genes. Thus, upstream regions of INO2 and INO4 are not crucial for transcriptional control of ICRE-dependent genes by inositol and choline. Interestingly, over-expression of INO2, but not of INO4, counteracted repression by phospholipid precursors. Possibly, a functional antagonism between INO2 and a negative regulator is the key event responsible for repression or de-repression.

Basic Helix-Loop-Helix Proteins↗

Fetal villosity and microvasculature of the bovine placentome in the second half of gestation.

The architecture of the fetal villous tree and its vasculature in the bovine placentome were studied in the second half of gestation using both conventional histology and histology of ink-filled blood vessels. These were compared with corrosion casts of plastic fillings of the vasculature, prepared for scanning electron microscopy. This combination of morphological methods allows perception of the villous tree throughout gestation from broad-conical to tall-conical form where branch ramification occurs mainly at right angles to the stem. The stem villus typically contains a single central artery and several peripheral veins arranged in parallel. The proximal branches to the stem, the intermediate villi, contain a central arteriole and accompanying venules. The distal branches, the terminal villi, enclose capillary convolutions which consist of an afferent arterial capillary limb, capillary loops and efferent venous capillary limbs. Vascular interconnections exist within the terminal villi, as capillaries or venules between the capillary convolutions, serially bridging them in up to 5 places, and as capillary anastomoses between the capillary loops. Coiling and sinusoidal dilatations of these loops develop near the end of gestation. The intraplacentomal rearrangement of villous trees with progressive gestation and their morphological vascular adaptations are discussed in relation to placental function, including the ever increasing need for transplacental substance exchange. This adaptation allows the blood to traverse the shortest possible arterioarteriolar route to the periphery of the trees where exchange takes place. The need for an increasing blood flow stimulates capillary growth and at the same time optimises the blood flow reaching the placental barrier represented by the vessel cast surface. The capillaries also carry the blood back into the very voluminous system of venules and veins where back diffusion may occur. The total volume of terminal villi of bovine placentome, the 'working part' of villous trees, hence distinctly increases with respect to the stem and intermediate villi, the 'supplying part' of the villous tree. In morphological terms the efficiency of the bovine transplacental diffusional exchange is higher than in the closely related 'co-ruminants' sheep and goats and distinctly higher when compared with the human placenta.

Animals↗

Determination of free and conjugated oestrogens in peripheral blood plasma, feces and urine of cattle throughout pregnancy.

In order to further characterize oestrogen production and metabolism during bovine pregnancy, free (f) and conjugated (c) estrone (E1), total free and conjugated oestrogens (tfcOe) and total free oestrogens (tfOe) were determined as marker oestrogens in blood plasma respectively in urine and feces of 10 pregnant cows. For the determination of individual oestrogens blood, urine and feces samples of days 240, 200, 160, 100, 60, 30, 10 and 5 prior to parturition were pooled and the free, sulfo (sc)- and glucuconjugated (gc) forms of E1, 17 beta-estradiol (E2 beta) and 17 alpha-estradiol (E2 alpha) were obtained following differential enzyme hydrolysis and separation by HPLC; hormone assay was by established RIA-procedures. FE1 and cE1 concentration in blood plasma, tfOe in feces and tfcOe in urine showed a similar pattern. A first rise occurred between days 110 and 120 of pregnancy, an additional overproportional rise commenced at around days 230-250. Highest concentrations were measured in feces (tfOe ca. 500 ng/g 1 day a. p.), followed by urine (tfcOe ca. 3.5 ng/mosmol 2 days a. p.) and blood plasma (fE1 ca. 8 nmol/l and cE1 ca. 20 nmol/l 2 days a. p.). Determination of individual oestrogens in blood plasma revealed that fE2 beta and fE2 alpha could only be found 10 days a. p. while the conjugated forms could already be detected on days 100 and 160 a. p. With 62% E1 was the dominant oestrogen, followed by E2 alpha (37%) and E2 beta (1.0%); E1 occurred predominantly as sulfate, E2 alpha and E2 beta predominantly as glucuronide. Main metabloite in feces was fE2 alpha (56.7%), followed by fE2 beta (32%) and fE1 (11.3%); conjugated oestrogens were not detected. Main metabolite in urine was scE1 followed by gcE2 alpha and gcE2 beta. ScE2 alpha and scE2 beta were not detected or were present in small quantities only. Hormonal changes over time were highly significant. Main product of placental oestrogen synthesis is scE1, the concentrations of f and c E2 beta and E2 alpha in plasma largely result from oestrogen metabolism and enterohepatic circulation.

Animals↗

Noninvasive method for measuring thrombus formation in patients after peripheral angioplasty using three-dimensional B-mode and color-coded Doppler ultrasonography.

Clinical investigations studying the effect of newer medications on such complex pathophysiology as the formation of an arterial or venous mural thrombus have been limited to clinical symptomatic endpoints. Biochemical markers so far have not been convincing in quantifying ongoing thrombus formation. Consequently, clinical development of new antithrombotic compounds has had to rely on clinical symptoms that occur either comparably late in the course of the disease and may therefore be influenced by many other factors, or on those symptoms that occur at a relatively low incidence rate. Both circumstances make studies for dose-finding and determination of optimal drug regimens more difficult and time consuming. Using conventional clinical noninvasive ultrasonography, the volume and geometry of a peripheral arterial segment can be measured with high sensitivity and reproducibility in healthy volunteers (% coefficient of variation = 8.01%). In patients, thrombus volume was monitored after peripheral transluminal angioplasty of the femoral artery. All patients received a standard anticoagulant treatment with heparin for 24 hours after the procedure. Volume measurements were performed at 20, 29, 44, 53, and 68 hours after angioplasty. When compared with the obstruction volume at 20 hours, a slight increase could be detected at 29, 44, and 53 hours. At 68 hours there was a significant increase in obstruction volume. This indicates that volume measurements may detect changes in the course of thrombus formation, related to the antithrombotic treatment regimen, at a level at which clinical symptoms may not be present.

Aged↗

[Investigations in central Hessia on the occurrence of estrogenic activity content of cattle feed].

In 21 farms which requested consultation for reasons of infertility problems feed samples (grass silage, n = 20; cornsilage, n = 19; hay, n = 9; cereal mixture, n = 3, brewers grains, n = 5, ensiled sugar beet tops, n = 1) were drawn for assay of free (aglycon) and glycosidic (glycosid) bound oestrogen activity. Following sample preparation and extraction, the oestrogenic activity was determined using a radioreceptorassay and only those samples leading to a 50% displacement of the 3H-estradiol-17 beta-tracer were classified as oestrogen-positive; values were expressed as ng 17 beta-estradiol equivalents per g dry matter. Selected samples clearly oestrogen-positive in the aglycone fraction were submitted to separation by HPLC and cytograms were established with the intention to allow an assignment of the oestrogenic activity to the following reference compounds, coumestrol, genistein, daidzein, formononetin, biochanin A, zeeralenon. With regard to free oestrogenic activity (aglycon) most of the grass silages were positive while-with one exception -the cornsilages were negative as were the hay-samples. The brewers grain samples were likewise positive and negative. Distinctly lower concentrations were found for the glycosidic bound oestrogenic activity with highest levels determined in hay. Results obtained after application of HPLC showed that the oestrogenic activity could particularly be attributed to daidzein and biochanin A. In the only oestrogen-positive cornsilage-sample the activity found corresponded with zearalenon. Types and concentrations of the oestrogenic activity allow the conclusion that negative effects on reproduction cannot be excluded.

Animal Feed↗

Hormonal state and effects of the use of an antiprogestin in bitches with pyometra.

The pathogenic significance of progesterone in pyometra in bitches was investigated by evaluating the stages of the oestrous cycles of 369 bitches with pyometra. Concentrations of progesterone and oestradiol were determined in 100 bitches with pyometra before ovariohysterectomy. Six bitches with pyometra with progesterone > 5 ng ml-1 and oestradiol < 25 pg ml-1 were treated with the antigestagen RU 46534 (6 mg kg-1, s.c.) twice on day 1 and once on days 2, 3 and 4; ovariohysterectomy was performed on day 6. Six control bitches that met the same criteria were ovariohysterectomized and uterine morphology was compared with that of the treated bitches. The effects of treatment were monitored by hormone, ultrasonographic imaging and histomorphological studies. The results confirm that pyometra may occur at any stage of the reproductive cycle and that most animals are in the phase of dioestrus. Uterine mass (g kg-1 bodymass) with versus without content was not different in treated bitches and was significantly lower (P < 0.01) than in the control bitches. In all six dogs general clinical conditions improved during the observation period; 23.5 +/- 11.1 h after the start of antiprogestin treatment a profuse, purulent vulval discharge was observed. The effusion was nearly complete at day 6. The maximal detectable uterine lumen varied between 23 and 39 mm in diameter, it was no longer detectable on day 6. Oestradiol concentrations remained constant while progesterone decreased with distinct individual variations. Morphometrical examination of the endometrium revealed no differences between groups. The data suggest that antigestagen treatment is a promising approach for treatment of pyometra in bitches.

Animals↗

Treatment of pyometra (cystic endometrial hyperplasia) in bitches with an antiprogestin.

On the basis of a previous study showing the effectiveness of an antiprogestin treatment on the involution of the pyometric uterus and general health of bitches, in the present open clinical study seven bitches with pyometra and progesterone concentrations > or = 2 ng ml-1 were treated with the antiprogestin RU 46534. The dose selected was 5 or 6 mg kg-1 body mass s.c., on the first day of treatment and 3 mg kg-1 body mass on days 2, 3, 4, 8, 12 and 16. Antibiotics were administered until day 16. A vulval discharge was observed within 12-24 h. In one bitch the dose of the antiprogestin had to be increased after day 4. In six bitches the uterine lumen became ultrasonographically undetectable between days 8 to 12; in one bitch some luminal material could still be detected on day 28. The number of blood leucocytes tended to increase after the onset of treatment but had returned to the upper normal range by day 16. In all dogs general condition and feed consumption improved rapidly and were normal within 8 days. No side effects were noted. Two of the dogs were mated subsequently and produced two healthy litters. These observations confirm those of a preceding study and show that the treatment of pyometra with an antiprogestin may lead to a clinical recovery. These results justify further studies to enable the optimum treatment regimen to be established.

Animals↗