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Biomedical subjects

B Hoffmann

Publications and source records attributed to B Hoffmann.

At least 127 records · Page 7Linked to original sources
PubMed1996

Comparison of plasmids of strains of Yersinia enterocolitica biovar 1A with the virulence plasmid of a pathogenic Y. enterocolitica strain.

The plasmid content of apathogenic Y. enterocolitica biovar 1A strains was determined and the plasmids were compared with the virulence plasmid of a pathogenic Y. enterocolitica strain. About 38% of the selected biovar 1A strains contained plasmids of different sizes ranging from 2.7 kb to more than 70 kb. Some of the larger plasmids had a size similar to that of the virulence plasmid of a pathogenic reference strain. The restriction patterns of these plasmids were different from the restriction pattern of the virulence plasmid of the pathogenic reference strain. Differences were also observed in hybridization studies with the virulence plasmid. The plasmids from 15 out of 16 biovar 1A strains showed no homology, whereas the plasmid of one biovar 1A strain partially hybridized to the virulence plasmid.

Animals↗
PubMed1996

Bendamustine hydrochloride activity against doxorubicin-resistant human breast carcinoma cell lines.

The cytotoxic activity of bendamustine hydrochloride was evaluated against human ovarian and breast carcinoma cell lines including cell lines resistant to cisplatin and doxorubicin in vitro. The relative degree of resistance to bendamustine hydrochloride was lower in all cell lines compared with cyclophosphamide, melphalan and BCNU, suggesting only incomplete cross-resistance. Furthermore lower levels of resistance were also observed in all breast cancer cell lines when bendamustine hydrochloride was compared with cisplatin. Bendamustine hydrochloride also presents good activity in cell line MCF 7 AD, which is approximately 80-fold resistant to doxorubicin compared with MCF 7. Basic glutathione levels and activity of glutathione-S-transferase showed no correlation to the IC50 values for bendamustine hydrochloride in the cell lines. When given at equitoxic concentrations, bendamustine hydrochloride consistently induced more DNA double-strand breaks than melphalan, cyclophosphamide or BCNU. In addition, removal of DNA double-strand breaks induced by bendamustine hydrochloride was relatively slow with the majority of DNA double-strand breaks still being detectable after 24 h. These findings indicate differences in the interaction between bendamustine hydrochloride and DNA, and may explain the lack of complete cross-resistance between bendamustine hydrochloride and the other alkylating agents.

Antibiotics, Antineoplastic↗
PubMed1996

Nitric oxide synthase in neurons and nerve fibers of lower airways and in vagal sensory ganglia of man. Correlation with neuropeptides.

The mediator accounting for the major relaxant responses to electrical field stimulation of human airways was previously identified as nitric oxide (NO). In the present study, we examined the distribution of the neuronal isoform of the NO-generating enzyme, nitric oxide synthase (bNOS, type I NOS) in nerve fibers of the human airways (trachea, large and small bronchi, bronchioli) as well as in human intrinsic and sensory ganglia of airway innervation by means of quantitative histochemistry (NADPH-diaphorase technique) and immunohistochemistry. Correlation with substance P (SP) and vasoactive intestinal peptide (VIP) was performed by double-labeling immunohistochemistry. NOS-containing nerve fibers were found to be present in the airway smooth muscle, around submucosal glands, around blood vessels and, very rarely, in the lamina propria. The innervation density of airway smooth muscle by NOS-containing nerve fibers decreased significantly from trachea to large-diameter bronchi to small-diameter bronchi, whereas NOS-containing nerve fibers were completely absent from bronchioli. Colocalization of NOS with VIP but not with SP was frequent in these nerve fibers. In airway intrinsic ganglia, the number of NOS-containing neuronal cell bodies increased from 57% in the trachea up to 83% in small bronchi. Around these perikarya, many nerve fibers displaying VIP-immunoreactive (VIP-IR) or SP-IR were found. In the superior vagal sensory (i.e., jugular) ganglion most of the neuronal cell bodies contained either NOS-IR or SP-IR; a colocalization of both was not as frequent. These data contribute to the understanding of the morphologic basis underlying the functional differences of the neural relaxant responses mediated by NO at different levels of the airway tree.

Bronchi↗
PubMed1995

DNA binding site of the yeast heteromeric Ino2p/Ino4p basic helix-loop-helix transcription factor: structural requirements as defined by saturation mutagenesis.

The inositol/choline-responsive element (ICRE) is an 11 bp cis-activating sequence motif with central importance for the regulated expression of phospholipid biosynthetic genes in the yeast Saccharomyces cerevisiae. The ICRE containing the CANNTG core binding sequence (E-box) of basic helix-loop-helix (bHLH) regulatory proteins is recognized by the heteromeric bHLH transcription factor Ino2p/Ino4p. In this study, we define the Ino2p/Ino4p consensus binding sequence (5'-WYTTCAYR-TGS-3') based on the characterization of all possible single nucleotide substitutions. Interestingly, this analysis also identified a single functional deviation (CACATTC) from the CANNTG core recognition element of bHLH proteins. The DNA binding specificities of different yeast bHLH proteins may now be explained by distinct nucleotide preferences especially at two positions immediately preceding the CANNTG core motif.

Base Sequence↗
PubMed1995

The cpc-2 gene of Neurospora crassa encodes a protein entirely composed of WD-repeat segments that is involved in general amino acid control and female fertility.

Phenotypic and molecular studies of the mutation U142 indicate that the cpc-2+ gene is required to activate general amino acid control under conditions of amino acid limitation in the vegetative growth phase, and for formation of protoperithecia in preparation for the sexual phase of the life cycle of Neurospora crassa. The cpc-2 gene was cloned by complementation of the cpc-2 mutation in a his-2ts bradytrophic background. Genomic and cDNA sequence analysis indicated a 1636 bp long open reading frame interrupted by four introns. The deduced 316 amino acid polypeptide reveals 70% positional identity over its full length with G-protein beta-subunit-related polypeptides found in humans, rat (RACK1), chicken, tobacco and Chlamydomonas. With the exception of RACK1 the function of these proteins is obscure. All are entirely made up of seven WD-repeats. Expression studies of cpc-2 revealed one abundant transcript in the wild type; in the mutant its level is drastically reduced. In mutant cells transformed with the complementing sequence, the transcript level, enzyme regulation and female fertility are restored. In the wild type the cpc-2 transcript is down-regulated under conditions of amino acid limitation. With cpc-2 a new element involved in general amino acid control has been identified, indicating a function for a WD-repeat protein that belongs to a class that is conserved throughout the evolution of eukaryotes.

Amino Acid Sequence↗
PubMed1994

Importance of general regulatory factors Rap1p, Abf1p and Reb1p for the activation of yeast fatty acid synthase genes FAS1 and FAS2.

The fatty acid synthase genes FAS1 and FAS2 of the yeast Saccharomyces cerevisiae are under transcriptional control of pathway-specific regulators of phospholipid biosynthesis. However, site-directed mutagenesis of the respective cis-acting elements upstream of FAS1 and FAS2 revealed that additional sequences activating both genes must exist. A deletion analysis of the FAS1 promoter lacking the previously characterized inositol/choline-responsive-element motif defined a region (nucleotides -760 to -850) responsible for most of the remaining activation potency. Gel-retardation experiments and in-vitro DNase footprint studies proved the binding of the general regulatory factors Rap1p, Abf1p and Reb1p to this FAS1 upstream region. Mutation of the respective binding sites led to a drop of gene activation to 8% of the wild-type level. Similarly, we also demonstrated the presence of a Reb1p-binding site upstream of FAS2 and its importance for gene activation. Thus, in addition to the previously characterized FAS-binding factor 1 interacting with the inositol/choline-responsive-element motif, a second motif common to the promoter regions of both FAS genes could be identified. Transcription of yeast fatty acid synthase genes is therefore subjected to both the pathway-specific control affecting genes of phospholipid biosynthesis and to the activation by general transcription factors allowing a sufficiently high level of constitutive gene expression.

Base Sequence↗
PubMed1994

The reconstituted ADP/ATP carrier activity has an absolute requirement for cardiolipin as shown in cysteine mutants.

Although the site-directed C73S mutation in the ADP/ATP carrier (AAC) AAC2 gene from Saccharomyces cerevisiae produced a glycerol-positive strain, indicating that the mutant AAC is active, on isolation and reconstitution in egg yolk phosphatidylcholine, the C73S AAC had no transport activity, whereas the wild-type AAC was fully active. Only on addition of cardiolipin was an exchange activity with the C73S AAC obtained. The AACs isolated from the other cysteine mutants did not (C244S) or only marginally (C271S) require cardiolipin for transport on reconstitution. [3H]Carboxyatractylate binding as a measure of incorporated AAC molecules was unchanged on addition of cardiolipin in all mutants, indicating that cardiolipin does not increase the incorporation of the AAC. It also shows that cardiolipin is required only for translocation and not for binding. The activity of the C73S mutant AAC shows half-saturation with cardiolipin at 2% by weight or at 1.15 mol % in the phosphatidylcholine vesicles. Other acidic phospholipids tested such as phosphatidylserine and phosphatidic acid did not activate. Among various cardiolipin derivatives, the selectivity for cardiolipin is high. Only monolysocardiolipin still retains 12% activity. After removal of the bulk of phospholipid, the content of bound phospholipids was assayed by 31P NMR. By unmasking with SDS, in the wild-type AAC and in the C73S AAC, 6.4 mol and only 1.3 and 2.9 mol of bound cardiolipin/mol of AAC dimer are found, respectively. Presumably, on isolation, cardiolipin is lost from the more labile C73S mutant AAC. Although the absolute requirement for cardiolipin is unique for the C73S AAC, it is concluded that in this mutant, the unmasking of the cardiolipin requirement demonstrates a general cardiolipin requirement of the wild-type AAC and of AACs from other sources.

Adenosine Diphosphate↗
PubMed1994

Lectin-histochemical analysis of glycans in ovine and bovine near-term placental binucleate cells.

Chorionic binucleate cells (BNC) occur in several ruminants including cow, deer, goat and sheep. They migrate through the chorionic tight junction to fuse with uterine epithelial cells and discharge their granules into maternal connective tissue. We have compared the BNC of near-term, resin-embedded, ovine and bovine placentae using 15 biotinylated lectins and an avidinperoxidase revealing system. There was pronounced conservation of saccharides between the two species. Several sub-types of N-glycan were present, with highly branched structures being abundant, as shown by Galanthus nivalis, Pisum sativum and Phaseolus vulgaris (leuko) agglutinins. Among the non-reducing terminal saccharides conserved were GalNAc alpha 1,3(Fuc alpha 1,2)-Gal beta 1,4GlcNAc beta 1-, GalNAc alpha 1,6Gal beta 1-, Gal beta 1-, Gal beta 1,4GlcNAc- and Gal beta 1,3GalNAc alpha 1- shown by Dolichos biflorus, Wisteria floribunda, Erythrina cristagalli, and Maclura pomifera agglutinins, respectively. Arachis hypogaea and Glycine max agglutinins tended to bind to bovine BNC at different stages of maturity, while fucosyl residues detectable by Tetragonolobus purpureus and Ulex europaeus-1 agglutinins were not observed in either species. The only major difference related to sialyl residues, with alpha 2,3-linked sialic acid being present in bovine (Maackia amurensis, Limax flavus) and alpha 2,6 sialic acid being present in ovine (Sambucus nigra agglutinin) cells. This conservation of glycan may be related to glycosylation of peptide hormones in the granules, and may thus be important in the targeting of these hormones to their receptors.

Animals↗
PubMed1994

Investigations on the use of C-21-steroids as precursors for placental oestrogen synthesis in the cow.

Cotyledonary homogenates from 220 and 270 day pregnant and term cows were incubated (NADPH- and NAD(+)-regenerating system) with 3H-pregnenolone and 3H-progesterone, respectively. Identification of metabolites was based on separation on HPLC and the respective retention times. On days 220/270 the major metabolite formed after incubation with 3H-pregnenolone was progesterone, followed by 17 alpha-hydroxyprogesterone and dehydroepiandrosterone/17 alpha-hydroxypregnenolone; the formation of estrone was low (up to 6%), while it was the major metabolite after incubation of pregnenolone with term placenta. At all stages of pregnancy investigated, the only metabolite found after incubation with 3H-progesterone was 17 alpha-hydroxyprogesterone. These data provide evidence that 17 alpha-hydroxyprogesterone is the endpoint of steroid biosynthesis in the bovine placenta along the delta 4-route and that oestrogen synthesis follows the delta 5-pathway. Based on the high activity of 3 beta-hydroxysteroiddehydrogenase/delta 5/4-isomerase also found on days 220/270, the key enzyme allowing for placental oestrogen synthesis in the cow seems to be cytochrome P450c17 alpha. Thus the situation in the cow is similar to that in the sheep and the increased turnover of pregnenolone into estrone may explain the decrease of placental progesterone production in the cow towards the end of gestation.

Animals↗
PubMed1994

Investigations on hormonal changes around parturition in the dog and the occurrence of pregnancy-specific non conjugated oestrogens.

Concentrations of progesterone and estradiol-17 beta were determined throughout pregnancy in 6 to 10 bitches (exp. 1); in experiment 2 peripartal changes of estradiol-17 beta, estrone, progesterone, cortisol, prolactin and growth hormone were determined in 5 bitches; in experiment 3 total unconjugated oestrogens were determined by radioimmunoassay and radioreceptorassay in placental tissue from 25, 53, 60 and 64 days pregnant bitches. No pregnancy specific increase of estradiol-17 beta could be observed; estradiol-17 beta levels decreased prior to parturition concomitant with the decrease of progesterone, suggesting a likewise luteal origin of estradiol-17 beta in the pregnant and non pregnant dog. Cortisol and growth hormone concentrations were elevated at the time of parturition, prolactin concentrations remained unchanged but were higher in pregnant than in non pregnant dogs. No hints in respect to a specific placental oestrogen production were obtained when examining placental tissue. The hypothesis is put forward that the high sensitivity of the haematopoietic system of the dog to oestrogen was an important factor in respect to evolution of endocrine control of pregnancy and parturition in this species which-in respect to placental oestrogen production-seems to be different from most other domestic animal species.

Animals↗
PubMed1994

Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO2 removal for adult respiratory distress syndrome.

The impact of a new therapy that includes pressure-controlled inverse ratio ventilation followed by extracorporeal CO2 removal on the survival of patients with severe ARDS was evaluated in a randomized controlled clinical trial. Computerized protocols generated around-the-clock instructions for management of arterial oxygenation to assure equivalent intensity of care for patients randomized to the new therapy limb and those randomized to the control, mechanical ventilation limb. We randomized 40 patients with severe ARDS who met the ECMO entry criteria. The main outcome measure was survival at 30 days after randomization. Survival was not significantly different in the 19 mechanical ventilation (42%) and 21 new therapy (extracorporeal) (33%) patients (p = 0.8). All deaths occurred within 30 days of randomization. Overall patient survival was 38% (15 of 40) and was about four times that expected from historical data (p = 0.0002). Extracorporeal treatment group survival was not significantly different from other published survival rates after extracorporeal CO2 removal. Mechanical ventilation patient group survival was significantly higher than the 12% derived from published data (p = 0.0001). Protocols controlled care 86% of the time. Average PaO2 was 59 mm Hg in both treatment groups. Intensity of care required to maintain arterial oxygenation was similar in both groups (2.6 and 2.6 PEEP changes/day; 4.3 and 5.0 FIO2 changes/day). We conclude that there was no significant difference in survival between the mechanical ventilation and the extracorporeal CO2 removal groups. We do not recommend extracorporeal support as a therapy for ARDS. Extracorporeal support for ARDS should be restricted to controlled clinical trials.

Adult↗
PubMed1994

Clinical and radiological evaluation of long-term results of stereotactic proton beam radiosurgery in patients with cerebral arteriovenous malformations.

Within a period of nearly 10 years, from October, 1980, to May, 1990, a total of 68 patients with a cerebral arteriovenous malformation (AVM) were referred to a radiosurgical center in the United States for stereotactic Bragg peak proton beam therapy. Radiosurgery was chosen as an alternative treatment, either because the AVM was considered to be of high surgical risk due to its size and/or location, or because the patient refused surgery. In 63 patients (92.6%), complete clinical and radiological follow-up examinations were available. Clinical and radiological long-term results were correlated to size and to the Spetzler-Martin scale of the AVM. With increasing size or higher grade on the Spetzler-Martin scale, the clinical results of proton beam therapy became progressively worse. Of 37 patients with an AVM between 3 and 6 cm in diameter, only one-third showed amelioration of their clinical symptoms, and two-thirds remained the same or even deteriorated after radiation treatment. The same results apply to patients with very large AVM's, of whom only one-third profited from proton beam therapy. Although 85.7% of the patients in Spetzler-Martin Grades I and II showed postirradiation amelioration of their clinical symptoms, this compares to only 54.2% of the patients in Grade III, and only 24% in Grade IV. In regard to the radiological results of proton beam therapy, complete obliteration during long-term observation was only detectable in 10 patients or 15.9%, which is less than one-sixth of the whole group of 63 patients. All of these obliterated AVM's were smaller than 3 cm. Almost 85% of the patients treated using stereotactic proton beam therapy did not show any angiographic change in the radiological appearance of their AVM. The results reported here indicate that radiosurgery using stereotactic proton beam therapy is ineffective for the treatment of medium- or large-sized AVM's and should not be recommended for patients harboring an AVM larger than 3 cm. If proton beam treatment is contemplated, it should be restricted to AVM's that are less than 3 cm in size and whose location makes them easily accessible only for proton beam therapy.

Adolescent↗
PubMed1994

[Aspects of questions about animal health and animal husbandry].

The public discussion concerning animal health not so much relates to classical diseases but rather concentrates on problems likely to result from the demand on the yield of animal production. Both, animal health and animal production have a high social value. A conflict might arise from those situations when animal production seems to interfere with animal health. Since the definition of an animal as healthy is not only a matter of science but also of ethics, also requiring a risk-benefit-analysis, the question of an acceptable denominator in respect to the ethics involved is put forward. The concept of a relative anthropocentric approach is presented, making a distinction between human dignity and the well-being of animals. The prospect in treatment and handling of animals should be an increase in humanity and only justifiable reasons would allow interference with animal development and its social environment. By profession the veterinarian is predestined to protect animal health and he is summoned to accept this responsibility and to objectively apply his expertise, also to further develop the propositions of modern European legislation on animal welfare. In this respect the demand on animal yield put forward by animal breeding requests special attention.

Animal Husbandry↗
PubMed1994

Morphological and hormonal changes after superovulation in cows treated with Neutra-PMSG.

Morphological changes in ovaries and hormonal changes as well as changes in Na, K, Ca, Mg, and P blood plasma levels were observed after superovulation induced by the administration of PMSG and the neutralization of this hormone with monoclonal antibodies Neutra-PMSG administered either 72 or 108 h later. The introduction of Neutra-PMSG 108 h after PMSG injection clearly decreases the number of surviving non-ovulated follicles with a diameter > 10 mm (1.7 +/- 0.8 vesicle in an individual cow on the average) in comparison to the group without Neutra-PMSG (19.4 +/- 9.5). The efficiency of ovulation in the group treated with Neutra-PMSG in the 108th h of the experiment (8.2 +/- 4.6 corpora lutea per cow on the average), did not differ statistically from the group treated with PMSG only (12.4 +/- 10.6). Early administration of Neutra-PMSG (72h), totally inhibits superovulation. Observations showed, that injection of Neutra-PMSG in the 108th h, caused a considerable decrease in the estradiol level, beginning with the 120th h of the experiment. Determination of the progesterone blood plasma level reflects the number of corpora lutea and can be helpful in evaluating the effects of superovulation. Superovulation did not effect the level of Na, K, Ca, Mg, and P in the blood plasma.

Animals↗
PubMed1993

Formation of retinoid X receptor homodimers leads to repression of T3 response: hormonal cross talk by ligand-induced squelching.

Thyroid hormone receptors (TRs) form heterodimers with retinoid X receptors (RXRs). Heterodimerization is required for efficient TR DNA binding to most response elements and transcriptional activation by thyroid hormone. RXRs also function as auxiliary proteins for several other receptors. In addition, RXR alpha can be induced by specific ligands to form homodimers. Here we report that RXR-specific retinoids that induce RXR homodimers are effective repressors of the T3 response. We provide evidence that this repression by RXR-specific ligands occurs by sequestering of RXR from TR-RXR heterodimers into RXR homodimers. This ligand-induced squelching may represent an important mechanism by which RXR-specific retinoids and 9-cis retinoic acid mediate hormonal cross talk among a subfamily of nuclear receptors activated by structurally unrelated ligands.

Animals↗
PubMed1993

Current-noise analysis of Na absorption in the embryonic coprodeum: stimulation by aldosterone and thyroxine.

The mechanism and regulation of sodium transport in the embryonic coprodeum of chicken were investigated with isolated epithelia in vitro by electrophysiological techniques. Electrogenic sodium transport (INa) was measured in Ussing chambers by the short-circuit current (Isc) technique and identified by the diuretic amiloride or by removal of sodium from the apical medium. Apical sodium channels and the kinetics of amiloride binding were investigated by current-noise analysis. Isc and INa were measured under control conditions and under the influence of in vitro incubation with aldosterone and thyroxine. At 20 days the embryonic coprodeum has an Isc of 12.6 +/- 1.4 microA/cm2 and a transepithelial resistance of 519 +/- 40 omega.cm2. Amiloride blocks 9.0 +/- 1.3 microA/cm2 of the Isc, which represents electrogenic Na+ absorption and can be inhibited by serosal ouabain. Aldosterone does not stimulate Isc or INa, whereas thyroxine increases Isc and INa about threefold. Aldosterone in combination with thyroxine increases Isc and INa further to about five- to sixfold. In both cases the hormonal stimulation can be totally blocked by spironolactone. Current-noise analysis of the apical Na+ entry step reveals amiloride-sensitive Na+ channels with a single-channel current of approximately 2.3 pA and a channel density of 9-16 million/cm2 under stimulated conditions. Half-maximal amiloride block occurs at 0.8-1 microM. The hormones stimulate Na+ absorption by increasing the Na+ channel density and not the single-channel current.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1993

V-erbA requires auxiliary proteins for dominant negative activity.

The avian v-erbA protein is an important example of a dominant negative oncogene. It has been identified as a highly mutated form of its cellular homolog, the thyroid hormone receptor alpha (TR-alpha), and its biological activity has been correlated with its repressor function on certain receptor-regulated genes. Although v-erbA has lost the hormone responsiveness of its cellular homolog, it has retained DNA-binding activity, and it has been implied that this function is required for repression and transformation. Here we demonstrate that v-erbA forms heterodimers with the retinoid X receptor (RXR-alpha). Only heteromeric v-erbA-RXR-alpha complexes show DNA-binding strong enough to account for its potent repressor function. In addition, v-erbA-RXR-alpha heterodimers specifically bind natural thyroid hormone-responsive elements (TREs) but not retinoic acid-responsive elements (RAREs). Repression of TRE-controlled gene expression by v-erbA requires the presence of RXR-alpha with the natural TREs tested. In contrast, natural RAREs investigated here do not bind the v-erbA-RXR-alpha heterodimer and also are not significantly repressed by v-erbA. Carboxy-terminal mutations that abolish v-erbA-RXR-alpha heterodimer formation also abolish v-erbA repressor activity. These data suggest that interaction of v-erbA with RXRs or similar auxiliary receptors is essential for the dominant negative activity of the v-erbA oncogene.

Base Sequence↗