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Biomedical subjects

B Hoffmann

Publications and source records attributed to B Hoffmann.

At least 55 records · Page 3Linked to original sources
PubMed2003

Hormonal and behavioural changes during the mating season and pregnancy in Alpine marmots (Marmota marmota).

Under natural and artificial conditions, Alpine marmots (Marmota marmota) are true hibernators with a single breeding season starting immediately upon emergence from hibernation. Over three mating and breeding seasons, hormonal and mating patterns of colony-housed reproductive female marmots were investigated after exit from hibernation. Blood samples were taken for progesterone, oestrogen and relaxin assays with parallel ultrasound investigations. Copulations were observed from the first day after exit from hibernation until the end of pregnancy and reached a maximum number on day 37 before parturition. Mating behaviour was observed between the dominant animals as well as between dominant and subdominant group members. In the first week after exit from hibernation, plasma progesterone was detected in half of the animals. During the third week, progesterone concentrations were significantly higher in pregnant than in non-pregnant animals or animals that had aborted. Immediately after emerging from hibernation, all successfully mated females showed higher serum relaxin values than non-successfully mated animals and this increase in relaxin concentration lasted until the end of pregnancy. The total concentration of oestrogen did not differ between pregnant and non-pregnant animals. The results of this study indicate that progesterone and relaxin might be useful indicators of early pregnancy in Alpine marmots.

Animals↗
PubMed2002

The neuron-specific Ca2+-binding protein caldendrin: gene structure, splice isoforms, and expression in the rat central nervous system.

Caldendrin is the founder member of a recently discovered family of calmodulin-like proteins, which are highly abundant in brain. In this study we examined the organization of the murine and human caldendrin gene as well as the expression pattern of transcripts for caldendrin and two novel splice variants. In addition the distribution of caldendrin in rat brain has been assessed by immunohistochemistry. Caldendrin is localized to the somatodendritic compartment of a subpopulation of mainly principal neurons in brain regions with a laminar organization and is present only at a subset of mature excitatory synapses. Caldendrin immunoreactivity (IR) is tightly associated with the cortical cytoskeleton, enriched in the postsynaptic density (PSD) fraction, and associates late during development with the synaptic cytomatrix. The expression is highly heterogenous within cortex, with highest levels of caldendrin IR in layer III of the piriform and layer II/III of the somatosensory cortex. The segregated cortical distribution to areas, which represent the most important primary sensory systems of the rodent brain, may reflect different requirements for dendritic Ca2+-signaling in these neurons. The presence of caldendrin in the PSD of distinct synapses may have important implications for Ca2+-modulated processes of synaptic plasticity.

Alternative Splicing↗
PubMed2002

Incidence and management of complications during posttraumatic early rehabilitation.

Early rehabilitation after traumatic brain injury has become a worldwide accepted interface between intensive care medicine and rehabilitation to aim for a better functional outcome of the surviving patients. So each chain can only be as strong as its weakest link, and there is still need for well defined quality standards depending on the medical demands during this period of treatment. Hence we were interested in quantifying the complications occurring until discharge to further rehabilitation with special regard on severe physical handicaps and organ failure necessitating surgical or intensive care therapy. Our results demonstrate that early rehabilitation is a part of intensive care medicine with enhanced approaches to preserve rehabilitation potential of the brain and for coma stimulation.

Brain Injuries↗
PubMed2002

Neurological and social long-term outcome after early rehabilitation following traumatic brain injury. 5-year report on 240 TBI patients.

The long term courses of patients after traumatic brain injury (TBI) are particularly influenced by the quality of neuropsychological rehabilitation and social reintegration. Though we do have data from different European countries about the success of surgery and intensive care, we don't know much about the long term courses, mirrored by the patients, their relatives and local physicians in their domestic environment. Supported by a pilot project of the government of Nordrhein--Westfalia we reviewed 252 patients with different grades of TBI, which were treated in our department from emergency to the end of early rehabilitation. At least 240 files could be completed, including observations up to 5 years after trauma (mean 26 months). 66% of the patients suffered from severe TBI according to the initial Glasgow Coma Scale (GCS), 23% showed moderate and 11% mild TBI. After discharge from early rehabilitation and during further treatment in rehabilitation hospitals patients with persistent vegetative state (PVS) did not show a significant benefit from therapy: Only 1 patient improved to GOS 3, fatal courses were observed in 3 patients, 11 patients remained unchanged. Patients with GOS 3 at the end of early rehabilitation on the other hand could improve in 51 cases to GOS 4 and 5. At the time of the actual investigation 32% of the patients reached GOS 5, 27% GOS 4. Unfavourable courses showed 21% (GOS 3), 5% (GOS 2) and 15% (GOS 1). Referred to the initial GCS only 16% of the severe, 27% of the moderate and 33% of the mild TBI could return to their former social activities and profession without any cuts. 145 of the total of surviving patients could return to their families, in the group of vegetative patients all except 1 patient were submitted for nursing homes. Only 58% of the patients practiced any kind of outpatient rehabilitation, a specialized neuropsychological training has been restricted to 7% of the patients. So we observe a significant gap between a high impact clinical medicine on one side and a deficient outpatient treatment on the other. At least many patients are standing alone after discharge from rehabilitation hospitals, resulting in prolonged stationary treatment with extensive costs to minimize damage from this situation. Our consequence for a more efficient treatment is, that we substantially need better programs by local administrations, insurance companies and employers for better and earlier reintegration to avoid isolation and unnecessary invalidation, especially of those patients with the best medical prognosis.

Adolescent↗
PubMed2002

The bovine placenta; a source and target of steroid hormones: observations during the second half of gestation.

Apart from estrone-3-sulfate (E1S) the bovine placenta produces progesterone (P4), though the corpus luteum is the major source of P4 responsible for maintaining pregnancy. So far the biological function of placental steroids in cattle is largely unknown. However, since the local availability of free estrone (E1) in the placenta seems to be controlled by sulfatase and sulfotranferase, the hypothesis was developed that placental estrogens and P4 might act as local regulatory factors. To test for such a function placentomes from 150, 220, 240, 270 days (D) pregnant and parturient cows were screened immunohistochemically for progesterone and estrogen receptors (PR, ER). PR were found at all stages in the caruncle in stromal cells and capillary pericytes but only at parturition in arterial walls. Percentage of PR-positive caruncular stromal cells (CSC) increased (P<0.05) from 51.8+/-2.6% at D150 to 58.9+/-1.8% at parturition. ER were detected in CSC, caruncular epithelial (CE) cells and in caruncular capillary pericytes. Mean percentage of ER-positive CSC decreased from 39.0+/-5.9% in pregnant cows to 17.5+/-8.3% at parturition (P<0.05). In CE all cells exhibited positive signals with the exception of those immediately surrounding large primary chorionic villi. Proliferation was assessed immunohistochemically by determining the percentage of Ki67-antigen positive cells. Highest values (P<0.001) were obtained for CE (58.0-68.3%), followed by the trophoblast (23.3-25.4%), CSC (10.6-45.3%) and the stroma of the chorionic villi (2.9-10.5%). A transient depression of proliferation in CSC between D150-270 (P<0.05) paralleled local estrogen tissue concentrations. The results suggest that placental estrogens and P4 are important factors controlling caruncular growth, differentiation and function.

Animals↗
PubMed2002

[Self-exercised health care and consultation of medical aid by single-parent mothers or fathers - results of a federal health survey].

PURPOSE: Single parents are at high risk of economical poverty and social deprivation. In this study we investigated the association of single parenthood with self-reported health, self-perceived mental disorders and the use of medical services. METHODS: The public users file of the German Health Survey 1998 were used for secondary analysis. Single-parent mothers aged 18 to 45 with at least one child under the age of 18 (n = 81) were compared with two control groups of the same age: mothers living in traditional nuclear families (n = 104) and women living in partnership status without children (n = 140). RESULTS: Single-parent mothers report less frequently than controls of a very good or excellent health status and more frequently of mental complaints (differences of single items of 10 to 15 percent). Feelings of discouragement and sadness are more common in this group. Overall, single-parent mothers do not use medical services more frequently than the control groups, but there are differences in the use of some specialists, especially psychotherapists. CONSEQUENCES: In respect of health, psychological stress is at a high level whereas the value of subjective health seems lower. The emphasis on situational parameters provides an insight into positive coping strategies and shifts the focus on influences that support health in a positive manner.

Adolescent↗
PubMed2001

A protein pre-organized to trap the nucleotide moiety of coenzyme B(12): refined solution structure of the B(12)-binding subunit of glutamate mutase from Clostridium tetanomorphum.

Uniformly (13)C,(15)N-labeled MutS, the coenzyme B(12)-binding subunit of glutamate mutase from Clostridium tetanomorphum, was prepared by overexpression from an Escherichia coli strain. Multidimensional heteronuclear NMR spectroscopic experiments with aqueous solutions of (13)C,(15)N-labeled MutS provided signal assignments for roughly 90% of the 1025 hydrogen, 651 carbon, and 173 nitrogen atoms and resulted in about 1800 experimental restraints. Based on the information from the NMR experiments, the structure of MutS was calculated, confirming the earlier, less detailed structure obtained with (15)N-labeled MutS. The refined analysis allowed a precise determination of the secondary and tertiary structure including several crucial side chain interactions. The structures of (the apoprotein) MutS in solution and of the B(12)-binding subunit in the crystal of the corresponding homologous holoenzyme from Clostridium cochlearium differ only in a section that forms the well-structured helix alpha1 in the crystal structure and that also comprises the cobalt-coordinating histidine residue. In the apoprotein MutS, this part of the B(12)-binding subunit is dynamic. The carboxy-terminal end of this section is conformationally flexible and has significant propensity for an alpha-helical structure ("nascent helix"). This dynamic section in MutS is a decisive element for the binding of the nucleotide moiety of coenzyme B(12) and appears to be stabilized as a helix (alpha1) upon trapping of the nucleotide of the B(12) cofactor.

Amino Acid Sequence↗
PubMed2001

The LIS1-related protein NUDF of Aspergillus nidulans and its interaction partner NUDE bind directly to specific subunits of dynein and dynactin and to alpha- and gamma-tubulin.

The NUDF protein of Aspergillus nidulans, which is required for nuclear migration through the fungal mycelium, closely resembles the LIS1 protein required for migration of neurons to the cerebral cortex in humans. Genetic experiments suggested that NUDF influences nuclear migration by affecting cytoplasmic dynein. NUDF interacts with another protein, NUDE, which also affects nuclear migration in A. nidulans. Interactions among LIS1, NUDE, dynein, and gamma-tubulin have been demonstrated in animal cells. In this paper we examine the interactions of the A. nidulans NUDF and NUDE proteins with components of dynein, dynactin, and with alpha- and gamma-tubulin. We show that NUDF binds directly to alpha- and gamma-tubulin and to the first P-loop of the cytoplasmic dynein heavy chain, whereas NUDE binds directly to alpha- and gamma-tubulin, to NUDK (actin-related protein 1), and to the NUDG dynein LC8 light chain. The data suggest a direct role for NUDF in regulation of the dynein heavy chain and an effect on other dynein/dynactin subunits via NUDE. The interactions between NUDE, NUDF, and gamma-tubulin suggest that this protein may also be involved in the regulation of dynein function. Additive interactions between NUDE and dynein and dynactin subunits suggest that NUDE acts as a scaffolding factor between components.

Active Transport, Cell Nucleus↗
PubMed2001

Radon permeability and radon exhalation of building materials.

High radon concentrations indoors usually depend on the possibilities of radon penetration from the surrounding soil into the buildings. Radon concentrations in dwellings up to 100 kBq/m3 were found in some special regions (i.e. Schneeberg/Saxony, Umhausen/Tyrol), where the soil shows a high uranium content and additionally, a fast radon transport in the soil is possible. To reduce the radon exposure of the inhabitants in these 'radon prone areas' it is necessary to look for building and insulating materials with low radon permeability. We examined several building materials, like cements, concretes and bricks of different constitutions for their diffusion coefficients and their exhalation rates. The insulating materials, like foils and bitumen were tested also on their radon tightness. The measurements were performed with an online radon measuring device, using electrostatic deposition of 218Po ions onto a surface barrier detector and subsequent alpha spectroscopy. The mean diffusion lengths for the investigated building materials range from lower than 0.7 mm (i.e. for plastic foil), up to 1.1 m for gypsum. The diffusion length R was calculated from the diffusion coefficient D with R = square root(D/lambda). If the thickness of the material is more than 3 times the diffusion length, then it is called radon-tight. The mean 222Rn exhalation rates for the building materials varied between 0.05 and 0.4 mBq/m2s. The samples were investigated as stones, plates, blocks, foils, coatings, powders etc., no statement can be made about working at the construction site of a building. Also the fabrication and processing of the materials has to be considered, because the material characteristics may have changed.

Air Pollutants, Radioactive↗
PubMed2001

Regulation of hisHF transcription of Aspergillus nidulans by adenine and amino acid limitation.

The hisHF gene of Aspergillus nidulans encodes imidazole-glycerole-phosphate (IGP) synthase, consisting of a glutamine amidotransferase and a cyclase domain. The enzyme catalyzes the fifth and sixth steps of histidine biosynthesis, which results in an intermediate of the amino acid and an additional intermediate of purine biosynthesis. An A. nidulans hisHF cDNA complemented a Saccharomyces cerevisiae his7Delta strain and Escherichia coli hisH and hisF mutant strains. The genomic DNA encoding the hisHF gene was cloned and its sequence revealed two introns within the 1659-bp-long open reading frame. The transcription of the hisHF gene of A. nidulans is activated upon amino acid starvation, suggesting that hisHF is a target gene of cross pathway control. Adenine but not histidine, both end products of the biosynthetic pathways connected by the IGP synthase, represses hisHF transcription. In contrast to other organisms HISHF overproduction did not result in any developmental phenotype of the fungus in hyphal growth or the asexual life cycle. hisHF overexpression caused a significantly reduced osmotic tolerance and the inability to undergo the sexual life cycle leading to acleistothecial colonies.

Adenine↗
PubMed2001

Regulation of the Aspergillus nidulans hisB gene by histidine starvation.

The hisB gene of the filamentous fungus Aspergillus nidulans encodes imidazole glycerol-phosphate dehydratase (E.C. 4.2.1.19), which catalyses the seventh enzymatic step in histidine biosynthesis. The gene was isolated and its deduced peptide sequence of 247 amino acids showed up to 54% identity with the IGPD enzymes of organisms comprising all three kingdoms. Expression of hisB cDNA in a Saccharomyces cerevisiae his3delta mutant strain functionally complemented the growth phenotype under histidine limitation. Addition of histidine did not affect hisB mRNA levels in A. nidulans wild-type cells. Histidine starvation conditions increased the hisB transcript level four-fold, suggesting regulation by a cross-pathway regulatory network. Deletion of the complete hisB open reading frame in A. nidulans strain A234 resulted in histidine auxotrophy. Additionally, hisB deletion strains were blocked from sexual fruiting body formation on medium containing low concentrations of histidine. This developmental phenotype of the hisB deletion mutant strain correlated with the induction of the cross-pathway control system.

Alcohol Oxidoreductases↗
PubMed2001

Transcription factor MIZ-1 is regulated via microtubule association.

A synthetic drug, T113242, activates low-density lipoprotein receptor (LDLR) transcription in the presence of sterols. T113242 also covalently binds to beta-tubulin and induces microtubule depolymerization. The myc-interacting zinc finger protein (MIZ-1) associates with microtubules, can bind directly to the LDLR promoter, and can activate LDLR transcription. MIZ-1 also binds to the promoter and activates transcription of other T113242-induced genes such as alpha(2) integrin. Soft X-ray, indirect immunofluorescence, and green fluorescent protein time-lapse microscopy reveal that MIZ-1 is largely cytoplasmic but accumulates in the nuclei of HepG2 cells upon treatment with T113242. Thus, MIZ-1 appears to be regulated by association with microtubules and may activate gene transcription in response to changes in the cytoskeleton.

Active Transport, Cell Nucleus↗
PubMed2001

Investigations on the activity of bovine placental oestrogen sulfotransferase and -sulfatase from midgestation to parturition.

To gain further information on the biological role of the high amounts of conjugated estrone (E1S) secreted by the bovine placenta, an in vitro assay system was developed to measure oestrogen sulfotransferase (OST) and oestrogen sulfatase (OS) activities in caruncular and cotyledonary homogenates and the respective subcellular fractions. Placental tissue was obtained from 150 (n = 3), 220 (n = 4), 240 (n = 3) and 270 days (n = 3) pregnant and parturient cows (n = 4). 3H-E1 and 3H-E1S served as substrates and 4-nitrophenyl sulfate potassium salt was used as a competitive inhibitor to block OS when testing for OST activity. OST-activity did not change during pregnancy and parturition and was higher (p < 0.001) in cotyledonary than in caruncular tissue with mean conversions (median) of 61.8% and 41.6% after 30 min of homogenate incubation. On a subcellular level OST-activity was clearly associated with the cytosol. OS-activity was higher (p < 0.001) in caruncular than in cotyledonary homogenates; it was constant during pregnancy (median of conversion: 88.0% and 66.4%, resp.), but was significantly decreased (p < 0.05) at parturition (median of conversion: 48.1% and 30.6%, resp.). On a subcellular level in both the cotyledon and the caruncle highest OS-activities were detected in the microsomal and the mitochondrial fractions. The decreased placentomal OS-activities in parturient cows are inconsistent with a substantial role of OS in the prepartal increase of free oestrogens. These results also suggest that bovine placental oestrogens may largely exert their action locally within the placentomes during most time of gestation as the enzymes catalyzing sulfoconjugation (i.e. inactivation of free oestrogens) and desulfation (i.e. activation of conjugated oestrogens) are expressed in close proximity to each other. In this respect the finding of oestrogen receptors in caruncular stromal cells is of particular interest.

Animals↗
PubMed2001

Transcriptional autoregulation and inhibition of mRNA translation of amino acid regulator gene cpcA of filamentous fungus Aspergillus nidulans.

The CPCA protein of the filamentous fungus Aspergillus nidulans is a member of the c-Jun-like transcriptional activator family. It acts as central transcription factor of the cross-pathway regulatory network of amino acid biosynthesis and is functionally exchangeable for the general control transcriptional activator Gcn4p of Saccharomyces cerevisiae. In contrast to GCN4, expression of cpcA is strongly regulated by two equally important mechanisms with additive effects that lead to a fivefold increased CPCA protein amount under amino acid starvation conditions. One component of cpcA regulation involves a transcriptional autoregulatory mechanism via a CPCA recognition element (CPRE) in the cpcA promoter that causes a sevenfold increased cpcA mRNA level when cells are starved for amino acids. Point mutations in the CPRE cause a constitutively low mRNA level of cpcA and a halved protein level when amino acids are limited. Moreover, two upstream open reading frames (uORFs) in the 5' region of the cpcA mRNA are important for a translational regulatory mechanism. Destruction of both short uORFs results in a sixfold increased CPCA protein level under nonstarvation conditions and a 10-fold increase under starvation conditions. Mutations in both the CPRE and uORF regulatory elements lead to an intermediate effect, with a low cpcA mRNA level but a threefold increased CPCA protein level independent of amino acid availability. These data argue for a combined regulation of cpcA that includes a translational regulation like that of yeast GCN4 as well as a transcriptional regulation like that of the mammalian jun and fos genes.

Alleles↗
PubMed2001

Sexual diploids of Aspergillus nidulans do not form by random fusion of nuclei in the heterokaryon.

The sexual stage of Aspergillus (Emericella) nidulans consists of cleistothecia containing asci, each with eight ascospores. The fungus completes the sexual cycle in a homokaryotic or a heterokaryotic mycelium, respectively. The common assumption for the last 50 years was that different nuclear types are not distinguishable when sexual development is initiated. When cultured on a medium limited for glucose supplemented with 2% sorbitol, sexual development of A. nidulans is slowed and intact tetrads can be isolated. Through tetrad analysis we found that unlike haploid nuclei fuse preferentially to the prezygotic diploid nucleus. When heterokaryons are formed between nuclei of different genetic backgrounds, then recombinant asci derived from opposite nuclei are formed exclusively. Strains in the same heterokaryon compatibility group with moderate differences in their genetic backgrounds can discriminate between the nuclei of a heterokaryon and preferentially form a hybrid diploid nucleus, resulting in 85% recombinant tetrads. A. nidulans strains that differ at only a single genetic marker fuse the haploid nuclei at random for formation of diploid nuclei during meiosis. These results argue for a genetically determined "relative heterothallism" of nuclear recognition within a heterokaryon and a specific recruitment of different nuclei for karyogamy when available.

Aspergillus nidulans↗