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Biomedical subjects

K Braun

Publications and source records attributed to K Braun.

At least 19 recordsLinked to original sources
PubMed2006

Regional and cellular distribution of the extracellular matrix protein tenascin-C in the chick forebrain and its role in neonatal learning.

The juvenile brain's pronounced synaptic plasticity in response to early experience and learning events is related to the fact that the genetically pre-programmed molecular machinery mediating neuronal development and synapse formation, is activated throughout postnatal brain development and thereby can be recruited for learning and long-term memory formation. In situ hybridization and immunocytochemistry experiments revealed that tenascin-C, one candidate molecule which we suspect to be involved in neonatal learning, is expressed in the forebrain of domestic chicks around the sensitive period during which auditory filial imprinting takes place. The involvement of tenascin-C in this juvenile learning task was tested by injections of monoclonal antibodies directed to distinct domains of the tenascin-C molecule into the avian prefrontal cortex analog, the medio-rostral nidopallium/mesopallium (formerly termed medio-rostral neostriatum/hyperstriatum ventrale), a forebrain area which has been shown to be critically involved in auditory filial imprinting. Injections of monoclonal antibody Tn 68, which is directed against a cell-binding domain of the tenascin-C molecule, strongly reduced the imprinting rate, as opposed to injections of the monoclonal antibody Tn 578, which binds to a domain involved in neurite outgrowth. Double labeling immunohistochemistry revealed that tenascin-C is associated with neurons which express the Ca(2+)-binding protein parvalbumin, and displays a staining pattern highly reminiscent of perineuronal nets of the extracellular matrix. These results indicate that a distinct domain of tenascin-C is functionally involved in the juvenile learning process of filial imprinting and further suggest a critical role of a specific neuronal subpopulation.

Age Factors↗
PubMed2006

Early neonatal and postweaning social emotional deprivation interferes with the maturation of serotonergic and tyrosine hydroxylase-immunoreactive afferent fiber systems in the rodent nucleus accumbens, hippocampus and amygdala.

The impact of early emotional experience on the development of serotonergic and dopaminergic fiber innervation of the nucleus accumbens, hippocampal formation and the amygdala was quantitatively investigated in the precocious rodent Octodon degus. Two animal groups were compared: 1) degus which were repeatedly separated from their parents during the first three postnatal weeks, after weaning they were individually reared in chronic social isolation and 2) controls which were reared undisturbed with their families. In the deprived animals 5-hydroxytryptamine-immunoreactive fiber densities were increased in the core region of the nucleus accumbens (up to 126%), in the central nucleus of the amygdala (up to 112%) and in the outer subregion of the dentate gyrus stratum moleculare (up to 149%), whereas decreased fiber densities were detected in the dentate subgranular layer (down to 86%) and in the stratum lacunosum of the hippocampal cornu ammonis region 1 (down to 86%). Tyrosine hydroxylase-immunoreactive fiber densities were increased in the core (up to 115%) and shell region (up to 113%) of the nucleus accumbens of deprived animals, whereas decreased fiber densities (down to 84%) were observed in the hilus of the dentate gyrus. In the stratum granulosum and subgranular layer the fiber densities increased up to 168% and 127% respectively. In summary, these results indicate that the postnatal establishment of the monoaminergic innervation of limbic areas is modulated in response to early emotional experience, and that this environmental morphological adaptation is highly region specific.

Adaptation, Physiological↗
PubMed2006

Geographical variation in antibiotic resistance profiles of Escherichia coli isolated from swine, poultry, beef and dairy cattle farm water retention ponds in Florida.

AIMS: The aim of this study was to assess geographical variation in multiple antibiotic resistance (MAR) profiles of livestock Escherichia coli as well as to evaluate the ability of MAR profiles to differentiate sources of faecal pollution. METHODS AND RESULTS: More than 2000 E. coli isolates were collected from water retention ponds and manure of swine, poultry, beef and dairy farms in south, central and north Florida, and analysed for MAR using nine antibiotics. There were significant differences in antibiotic resistance of E. coli by season and livestock type for more than one antibiotic, but regional differences were significant only for ampicillin. Over the three regions, discriminant analysis using MAR profiles correctly classified 27% of swine, 49% of poultry, 56% of beef and 51% of dairy isolates. CONCLUSIONS: Regional variations in MAR combined with moderate discrimination success suggest that MAR profiles of E. coli may only be marginally successful in identifying sources of faecal pollution. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates the existence of regional and seasonal differences in MAR profiles as well as the limited ability of MAR profiles to discriminate among livestock sources.

Agriculture↗
PubMed2005

Endocrine and behavioural plasticity in response to juvenile stress in the semi-precocial rodent Octodon degus.

The present study in the South American rodent Octodon degus shows for the first time that the postnatal development of hypothalamic-pituitary-adrenal axis function in this semi-precocial species differs from that of altricial rodents, i.e. rats or mice, in several aspects. Our experiments revealed a particular pattern of hypothalamic-pituitary-adrenal axis activity during the first 3 weeks of life characterized by (i) a period of low plasma glucocorticoid concentrations, during which (ii) brief stress exposure (1 h parental separation) is able to elevate glucocorticoids significantly. In addition, (iii) repeated stress exposure (1 h parental separation daily) during the first 3 weeks of life resulted in females, but not in males, in an attenuated separation-induced increase of glucocorticoids, and a higher behavioural activity in both sexes at postnatal day 21. These data indicate that parental separation early in life acts as a 'strong' stressor in this species, which on the long run can alter endocrine stress response at the time of weaning in a sex-specific manner. These findings support the role of the hypothalamic-pituitary-adrenal axis as one of the key factors mediating the effects of early life stress on the neuronal network and behaviour in O. degus.

Acute Disease↗
PubMed2005

Opiate modulation of monoamines in the chick forebrain: possible role in emotional regulation?

Numerous studies have shown that the opiate system is crucially involved in emotionally guided behavior. In the present study, we focussed on the medio-rostral neostriatum/hyperstriatum ventrale (MNH) of the chick forebrain. This avian prefrontal cortex analogue is critically involved in auditory filial imprinting, a well-characterized juvenile emotional learning event. The high density of mu-opiate receptors expressed in the MNH led to the hypothesis that mu-opiate receptor-mediated processes may modulate the glutamatergic, dopaminergic, and/or serotonergic neurotransmission within the MNH and thereby have a critical impact on filial imprinting. Using microdialysis and pharmaco-behavioral approaches in young chicks, we demonstrated that: the systemic application of the mu-opiate receptor antagonist naloxone (5, 50 mg/kg) significantly increased extracellular levels of 5-HIAA and HVA; the systemic application of the specific mu-opiate receptor agonist DAGO (5 mg/kg) increased the levels of HVA and taurine, an effect that was antagonized by simultaneously applied naloxone (5 mg/kg); the local application of DAGO (1 mM) had no effects on 5-HIAA, HVA, glutamate, and taurine, however, the effects of systemically injected naloxone (5 mg/kg) were abolished by simultaneously applied DAGO (1 mM); the systemic application of naloxone (5 mg/kg) increased distress behavior (measured as the duration of distress vocalization during separation from the peer group). These results are in line with our hypothesis that the mu-opiate receptor-mediated modulation of serotonergic and dopaminergic neurotransmission alters the emotional and motivational status of the animal and thereby may play a modulatory role during filial imprinting in the newborn animal.

Analgesics, Opioid↗
PubMed2005

Early social environment interferes with the development of NADPH-diaphorase-reactive neurons in the rodent orbital prefrontal cortex.

The influence of early parental deprivation on the development of NADPH-diaphorase-(NO-synthase) reactive neuron numbers in subregions of the orbital prefrontal cortex (ventrolateral orbital, lateral orbital, and agranular insular cortex) was quantitatively investigated in the precocious lagomorph Octodon degus. Forty-five-day-old degus from three groups were compared: (1) repeated parental separation: degus that were repeatedly separated from their parents during the first three postnatal weeks and thereafter raised in undisturbed social conditions; (2) chronic isolation: degus that were raised under undisturbed social conditions until postnatal day 21, and then were reared in chronic social isolation; and (3) control: degus that were reared undisturbed in their families. Compared to the control animals the ventrolateral orbital prefrontal cortex and agranular insular cortex of the two deprived groups displayed significantly decreased density of NADPH-diaphorase-reactive neurons (down to 62% in the ventrolateral orbital prefrontal cortex of males, 70% in the agranular insular cortex, and in the lateral orbital prefrontal cortex 80% in both genders). These results confirm that early changes of social environment interferes with the development of limbic circuits, which might determine normal or pathological behaviors in later life.

Animals↗
PubMed2005

The chicken immediate-early gene ZENK is expressed in the medio-rostral neostriatum/hyperstriatum ventrale, a brain region involved in acoustic imprinting, and is up-regulated after exposure to an auditory stimulus.

The immediate-early gene zenk (an acronym for the avian orthologue of the mammalian genes zif-268, egr-1, ngfi-a and krox-24) has been extensively employed, in studies on oscine birds, as a marker of neuronal activity to reveal forebrain structures that are involved in the memory processes associated with the acquisition, perception and production of song. Audition-induced expression of this gene, in brain, has also recently been reported for the domestic chicken (Gallus gallus domesticus) and the Japanese quail (Coturnix coturnix japonica). Whilst the anatomical distribution of zenk expression was described for the quail, corresponding data for the chicken were not reported. We have, therefore, used in situ hybridisation to localise the mRNA that encodes the product of the zenk gene (which we call ZENK) within the brain of the 1-day-old chick. We demonstrate that this transcript is present in a number of forebrain structures including the medio-rostral neostriatum/hyperstriatum ventrale (MNH), a region that has been strongly implicated in auditory imprinting (which is a form of recognition memory), and Field L, the avian analog of the mammalian auditory cortex. Because of this pattern of gene expression, we have compared the level of the ZENK mRNA in chicks that have been subjected to a 30-min acoustic imprinting paradigm and in untrained controls. Our results reveal a significant increase (P< or =0.05) in the level of the ZENK mRNA in MNH and Field L, and in the two forebrain hemispheres; no increase was seen in the ectostriatum, which is a visual projection area. The data obtained implicate the immediate-early gene, zenk, in auditory imprinting, which is an established model of juvenile learning. In addition, our results indicate that the ZENK mRNA may be used as a molecular marker for MNH, a region that is difficult to anatomically and histochemically delineate.

Acoustic Stimulation↗
PubMed2005

Early socio-emotional experience induces expression of the immediate-early gene Arc/arg3.1 (activity-regulated cytoskeleton-associated protein/activity-regulated gene) in learning-relevant brain regions of the newborn chick.

We have cloned a full-length complementary DNA from the chicken (Gallus gallus domesticus), which encodes a polypeptide that exhibits approximately 75% identity to the product of the mammalian gene Arc (activity-regulated cytoskeleton-associated protein), also known as arg3.1 (activity-regulated gene). Since this gene is an immediate-early gene that has been suggested to play a role in synaptic plasticity and learning and memory processes, its expression has been analyzed in a juvenile form of learning, namely, filial imprinting. Our results demonstrate that Arc/arg3.1 mRNA is detectable in the newborn chick brain, and that at this early age the level of this transcript can be altered by brief sensory/emotional experience. After postnatal exposure to a novel 30-min auditory imprinting stimulus, Arc/arg3.1 mRNA was found to be significantly increased in two higher associative areas, the mesopallium intermediomediale (P = 0.002) and the nidopallium dorso-caudale (P = 0.031), compared with naïve controls. The transcript level was also significantly elevated after imprinting in Area L pallii (P=0.045), which is analogous to the mammalian auditory cortex. In addition, increases were seen in the medio-rostral nidopallium/mesopallium (P = 0.054), which is presumed to be the analog of the mammalian prefrontal cortex, and the hyperpallium intercalatum (P = 0.054), but these did not quite reach significance. We discuss these data in the light of those obtained in an earlier study, in the same paradigm, for the avian immediate-early gene, zenk (an acronym for zif-268, egr-1, ngfi-a and krox-24, which are different names for the orthologous mammalian gene). We conclude that, although both the Arc/arg3.1 and zenk genes are induced by auditory imprinting, they are significantly up-regulated in different learning-relevant brain regions. It is, therefore, evident that they must be activated by different mechanisms.

Acoustic Stimulation↗
PubMed2005

Development and characterization of drug delivery systems for targeting mammalian cells and tissues: a review.

Recent advances in the development of diagnostics and therapeutics in the fields of recombinant biochemistry, solid phase peptide synthesis as well as in galenical research have resulted in highly specific and efficient components. Presently, millions of patients can profit from these new therapeutic modalities. The application of an effective anti-tumor dose of drugs can lead to marked toxicity in patients. Therefore, safe and efficient possibilities to transport these compounds to the target are of outmost importance. The importance of drug delivery is pivotal in the wide area of pharmacological research. However, until now, this issue is still to be solved. The main goal of every drug delivery system is the delivery of a precise amount of a drug at a pre-programmed rate to the desired location in order to achieve the necessary drug concentration in the targeted organ for effective treatment. The key problem still remains the achievement of curative doses in a pharmacologically active state in the desired target while avoiding side effects. Although respectable advances can be recognized in this field, the currently applied mechanisms for the transport of therapeutic molecules across biological membranes still remain far from being efficient. Helper molecules could improve delivery to desired target sites. Presently, a number of efforts are made and a huge spectrum of biochemical, biological, medical, pharmaceutical and physical possibilities are arising. However, the design and development of successful therapies based on this technology still remains a great challenge.

Animals↗
PubMed2004

Assessment of the performance of the Ames II assay: a collaborative study with 19 coded compounds.

Nineteen coded chemicals were tested in an international collaborative study for their mutagenic activity. The assay system employed was the Ames II Mutagenicity Assay, using the tester strains TA98 and TAMix (TA7001-7006). The test compounds were selected from a published study with a large data set from the standard Ames plate-incorporation test. The following test compounds including matched pairs were investigated: cyclophoshamide, 2-naphthylamine, benzo(a)pyrene, pyrene, 2-acetylaminofluorene, 4,4'-methylene-bis(2-chloroaniline), 9,10-dimethylanthracene, anthracene, 4-nitroquinoline-N-oxide, diphenylnitrosamine, urethane, isopropyl-N(3-chlorophenyl)carbamate, benzidine, 3,3'-5,5'-tetramethylbenzidine, azoxybenzene, 3-aminotriazole, diethylstilbestrol, sucrose and methionine. The results of both assay systems were compared, and the inter-laboratory consistency of the Ames II test was assessed. Of the eight mutagens selected, six were correctly identified with the Ames II assay by all laboratories, one compound was judged positive by five of six investigators and one by four of six laboratories. All seven non-mutagenic samples were consistently negative in the Ames II assay. Of the four chemicals that gave inconsistent results in the traditional Ames test, three were uniformly classified as either positive or negative in the present study, whereas one compound gave equivocal results. A comparison of the test outcome of the different investigators resulted in an inter-laboratory consistency of 89.5%. Owing to the high concordance between the two test systems, and the low inter-laboratory variability in the Ames II assay results, the Ames II is an effective screening alternative to the standard Ames test, requiring less test material and labor.

International Cooperation↗
PubMed2003

Early social deprivation alters monoaminergic afferents in the orbital prefrontal cortex of Octodon degus.

The influence of early parental deprivation on the development of tyrosine hydroxylase- and 5-hydroxytryptamine-immunoreactive fiber innervation of subregions of the orbital prefrontal cortex (ventrolateral orbital, lateral orbital and agranular insular cortex) was quantitatively investigated in the precocious lagomorph Octodon degus. Forty-five-day-old degus from two groups were compared: 1) degus which were repeatedly separated from their parents during the first three postnatal weeks, and after weaning they were reared in social isolation; and 2) degus which were reared undisturbed in their families. Compared with the normal control animals the ventrolateral orbital prefrontal cortex and agranular insular cortex of the deprived animals displayed significantly increased density of tyrosine hydroxylase-immunoreactive fibers (up to 172% in the ventrolateral orbital prefrontal cortex and up to 143% in the agranular insular cortex). The lateral orbital prefrontal cortex showed increased 5-hydroxytryptamine-positive fiber densities (up to 118%). This altered balance between the serotonergic and dopaminergic cortical innervation in the orbital prefrontal cortex may reflect an anatomical and functional adaptation, which may be triggered by an altered activity of these transmitter systems during the phases of parental separation and social isolation.

Afferent Pathways↗
PubMed2003

Mother's voice "buffers" separation-induced receptor changes in the prefrontal cortex of octodon degus.

Although the potential vulnerability of the postnatally developing brain toward adverse environmental influences is generally recognized, relatively little is known about the basic mechanisms involved. The plasticity and adaptability of the postnatally developing brain in response to adverse emotional experiences was analyzed in the South American Octodon degus. Our study revealed that repeated brief separation from the parents and exposure to an unfamiliar environment induces an up-regulation of dopamine (D1) and 5-hydroxytrytamine (5HT1(A))-receptor density in the precentral medial, anterior cingulate, prelimbic and infralimbic cortices in female pups. No significant changes of gamma aminobutyric acid (GABA(A)) receptor density were found in deprived animals of both genders. The acoustic presence of the mother during parental separation suppressed the D1-receptor up-regulation as well as the 5-HT1(A)-receptor up-regulation, again only in the female pups. These results demonstrate that that early adverse emotional experience alters aminergic function within the prefrontal cortex in the female but not the male brain. The mother's voice, a powerful emotional signal, can protect the developing cortex from separation-induced receptor changes.

Acoustic Stimulation↗
PubMed2003

Haloperidol impairs auditory filial imprinting and modulates monoaminergic neurotransmission in an imprinting-relevant forebrain area of the domestic chick.

In vivo microdialysis and behavioural studies in the domestic chick have shown that glutamatergic as well as monoaminergic neurotransmission in the medio-rostral neostriatum/hyperstriatum ventrale (MNH) is altered after auditory filial imprinting. In the present study, using pharmaco-behavioural and in vivo microdialysis approaches, the role of dopaminergic neurotransmission in this juvenile learning event was further evaluated. The results revealed that: (i) the systemic application of the potent dopamine receptor antagonist haloperidol (7.5 mg/kg) strongly impairs auditory filial imprinting; (ii) systemic haloperidol induces a tetrodotoxin-sensitive increase of extracellular levels of the dopamine metabolite, homovanillic acid, in the MNH, whereas the levels of glutamate, taurine and the serotonin metabolite, 5-hydroxyindole-3-acetic acid, remain unchanged; (iii) haloperidol (0.01, 0.1, 1 mm) infused locally into the MNH increases glutamate, taurine and 5- hydroxyindole-3-acetic acid levels in a dose-dependent manner, whereas homovanillic acid levels remain unchanged; (iv) systemic haloperidol infusion reinforces the N-methyl-d-aspartate receptor-mediated inhibitory modulation of the dopaminergic neurotransmission within the MNH. These results indicate that the modulation of dopaminergic function and its interaction with other neurotransmitter systems in a higher associative forebrain region of the juvenile avian brain displays similar neurochemical characteristics as the adult mammalian prefrontal cortex. Furthermore, we were able to show that the pharmacological manipulation of monoaminergic regulatory mechanisms interferes with learning and memory formation, events which in a similar fashion might occur in young or adult mammals.

Acoustic Stimulation↗
PubMed2003

Hypercontractile heart failure caused by catecholamine therapy in premature neonates.

UNLABELLED: Catecholamine treatment for hypotension is common practice in neonatal intensive care units. In the presence of left ventricular hypertrophy, the positive inotropic action of catecholamines with mainly beta-receptor specificity can lead to excessive hypercontractility and paradoxical hypotension. This reports presents two cases of hypercontractile heart failure during beta-agonist treatment in very low birthweight (VLBW) infants. Both patients (27 wk, 5 d; and 26 wk, 6 d of gestation) underwent surgical arterial duct ligation and coarctation repair. After operation they developed arterial hypotension that failed to respond to epinephrine (adrenaline) or dobutamine treatment. Echocardiography demonstrated a complete systolic obliteration of the left ventricular cavity. Epinephrine and dobutamine were stopped, and norepinephrine (noradrenaline) was successfully used to control the hypotension. CONCLUSION: Treatment of hypotension with beta-agonists in VLBW infants with left ventricular hypertrophy can lead to hypercontractility and left ventricular obliteration with paradoxical hypotension. Careful echocardiographic monitoring is indicated in such cases.

Adrenergic Agonists↗
PubMed2003

Enzymatic synthesis of N-acetyllactosamine in aqueous-organic reaction media.

Beta-galactosidase from Bacillus circulans was used for the biocatalytic transfer of D-galactose (D-Gal) from o-nitrophenyl-beta-D-galactoside (ONPG) to the O-4 position of 2-acetamido-2-deoxy-D-glucopyranose (D-GlcNAc) forming the disaccharide N-acetyllactosamine (LacNAc, beta-D-Gal-(1 --> 4)-D-GlcNAc). In order to investigate the potential of this biocatalytic synthesis, first the optimal reactant ratio in an aqueous buffer system was determined. On the basis of these standard conditions we then performed reactions in aqueous-organic media applying organic cosolvents of different structure and polarity in various amounts. In this way we received in some cases appreciably better results than without organic cosolvent. The highest obtainable disaccharide yield was 50% in a mixture of 20% (v/v) cyclohexane/80% buffer versus 35% in buffer solution alone.

Amino Sugars↗
PubMed2002

[Successful long-term treatment of multiple metastases from renal cell carcinoma: combination of stereotactically guided percutaneous single-dose convergent beam irradiation and surgery].

The case of a patient suffering from renal cell carcinoma and recurrent brain metastases shows how the survival period can be significantly prolonged by a combination of stereotactically guided percutaneous single-dose convergent beam irradiation and surgery. This 58-year-old man's left kidney was completely excised because of a renal cell carcinoma. After 18 months and 25 months, respectively, a right frontal brain metastasis was operated on. In the next 7 years, biannual MRI checks were carried out which successively showed five different brain metastases, each of which was immediately subjected to single-dose stereotactic irradiation (median dosage: 20 Gy prescribed to the 80% isodose). In the following 2 years, operations were carried out on two metastases which could not be treated by radiation because of their considerable size and partial compression of the ventricle. In the next 3 years, four more brain metastases were subjected to single-dose stereotactic irradiation. There were no metastases in the other organs. At present, the patient is in good clinical condition and mobile. A negative prognosis is usually delivered for patients suffering from renal cell carcinoma and brain metastasis. However, in individual cases, the survival period can be significantly prolonged by regular MRI examinations and a combination of neurosurgery and single-dose stereotactic irradiation.

Brain Neoplasms↗
PubMed2002

Detection and quantification of the soluble form of the human erythropoietin receptor (sEpoR) in the growth medium of tumor cell lines and in the plasma of blood samples.

The erythropoietin receptor (EpoR) belongs to the cytokine superfamily and is a type I transmembrane protein. Like other members of this family, EpoR is also synthesized as a soluble form, and is subsequently secreted by the cell. To investigate whether soluble EpoR (sEpoR) is expressed in human tumor cell lines, we developed a sensitive quantitative ELISA, using an anti-human EpoR antibody and recombinant sEpoR as standard control. With this ELISA, sEpoR could be detected in the supernatant of human tumor cell lines. Analysis of blood samples showed that sEpoR was coprecipitated during coagulation. Therefore only plasma was suitable for analysis and first measurements of plasma samples were investigated. In conclusion, an ELISA to quantify the sEpoR was established and the expression of sEpoR in human tumor cell lines was demonstrated for the first time.

Adult↗