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B Hartmann

Publications and source records attributed to B Hartmann.

At least 19 recordsLinked to original sources
PubMed1999

NF-kappa B binding mechanism: a nuclear magnetic resonance and modeling study of a GGG --> CTC mutation.

We present the solution structure of the nonpalindromic 16 bp DNA 5'd(CTGCTCACTTTCCAGG)3'. 5'd(CCTGGAAAGTGAGCAG)3' containing a mutated kappaB site for which the mutation of a highly conserved GGG tract of the native kappaB HIV-1 site to CTC abolishes NF-kappaB binding. 1H and 31P NMR spectroscopies have been used together with molecular modeling to determine the fine structure of the duplex. NMR data show evidence for a BI-BII equilibrium of the CpA.TpG steps at the 3'-end of the oligomer. Models for the extreme conformations reached by the mutated duplex (denoted 16M) are proposed in agreement with the NMR data. Since the distribution of BII sites is changed in the mutated duplex compared to that of the native duplex (denoted 16N), large differences are induced in the intrinsic structural properties of both duplexes. In particular, in BII structures, 16M shows a kink located at the 3'-end of the duplex, and in contrast, 16N exhibits an intrinsic global curvature toward the major groove. Whereas 16N can reach a conformation very favorable for the interaction with NF-kappaB, 16M cannot mimic such a conformation and, moreover, its deeper and narrower major groove could hinder the DNA-protein interactions.

Binding Sites↗
PubMed1998

Solution structure of a non-palindromic 16 base-pair DNA related to the HIV-1 kappa B site: evidence for BI-BII equilibrium inducing a global dynamic curvature of the duplex.

1H and 31P NMR spectroscopy have been used together with molecular modelling to determine the fine structure of a non-palindromic 16 bp DNA containing the NF-kappa B binding site. Much emphasis has been placed upon NMR optimization of both two-dimensional 31P NMR techniques to extract structural information defining the phosphodiester backbone conformation and selective homonuclear 2D COSY experiments to determine sugar conformations. NMR data show evidence for a dynamic behaviour of steps flanking the ten base-pairs of the NF-kappa B binding site. A BI-BII equilibrium at these steps is demonstrated and two models for each extreme conformation are proposed in agreement with NMR data. In the refined BII structures, the NF-kappa B binding site exhibits an intrinsic curvature towards the major groove that is magnified by the four flanking steps in the BII conformation. Furthermore, the base-pairs are translated into the major groove. Thus, we present a novel mode of dynamic intrinsic curvature compatible with the DNA curvature observed in the X-ray structure of the p50-DNA complex.

DNA, Viral↗
PubMed1998

Flexibility of the B-DNA backbone: effects of local and neighbouring sequences on pyrimidine-purine steps.

The structurally correlated dihedral angles epsilon and zeta are known for their large variability within the B-DNA backbone. We have used molecular modelling to study both energetic and mechanical features of these variations which can produce BI/BII transitions. Calculations were carried out on DNA oligomers containing either YpR or RpY dinucleotides steps within various sequence environments. The results indicate that CpA and CpG steps favour the BI/BII transition more than TpA or any RpY step. The stacking energy and its intra- and inter-strand components explain these effects. Analysis of neighbouring base pairs reveals that BI/BII transitions of CpG and CpA are easiest within (Y)n(R)n sequences. These can also induce a large vibrational amplitude for TpA steps within the BI conformation.

Base Composition↗
PubMed1998

The wingless gene is required for embryonic brain development in Drosophila.

We have studied the role of the wingless gene in embryonic brain development of Drosophila. wingless is expressed in a large domain in the anlage of the protocerebrum and also transiently in smaller domains in the anlagen of the deutocerebrum and tritocerebrum. Elimination of the wingless gene in null mutants has dramatic effects on the developing protocerebrum; although initially generated, approximately one half of the protocerebrum is deleted in wingless null mutants by apoptotic cell death at late embryonic stages. Using temperature sensitive mutants, a rescue of the mutant phenotype can be achieved by stage-specific expression of functional wingless protein during embryonic stages 9-10. This time period correlates with that of neuroblast specification but preceeds the generation and subsequent loss of protocerebral neurons. Ectopic wingless over-expression in gain-of-function mutants results in dramatically oversized CNS. We conclude that wingless is required for the development of the anterior protocerebral brain region in Drosophila. We propose that an important role of wingless in this part of the developing brain is the determination of neural cell fate.

Animals↗
PubMed1998

Low levels of serum inhibin A and inhibin B in women with hypergonadotropic amenorrhea and evidence of high levels of activin A in women with hypothalamic amenorrhea.

OBJECTIVE: To examine serum levels of inhibin A, inhibin B, and activin A in women with secondary hypergonadotropic or hypothalamic amenorrhea. DESIGN: Retrospective study. SETTING: Universities of Udine, Pisa, and Modena in Italy, and of Wien in Austria. PATIENT(S): Forty women with idiopathic premature ovarian failure (POF), 23 women with hypogonadotropic hypothalamic amenorrhea, 40 healthy postmenopausal women, and 40 age-matched women with normal ovarian function (controls). INTERVENTION(S): Blood samples were collected between 8 and 9 AM. MAIN OUTCOME MEASURE(S): Serum levels of inhibin A, inhibin B, and activin A. RESULT(S): Women with POF had lower concentrations of serum inhibin A and inhibin B than women with hypothalamic amenorrhea and fertile controls, and the difference between these concentrations was statistically significant. Levels of inhibin A and inhibin B were low in postmenopausal women and were no different than in women with POF. Serum levels of activin A were not significantly different among women with POF, fertile controls, and postmenopausal women. Women with hypogonadotropic hypothalamic amenorrhea had higher activin A values than did controls. No significant correlation was found between the level of inhibin A or inhibin B and the length of amenorrhea or the level of FSH. CONCLUSION(S): Low levels of circulating inhibins A and B, but not activin A, reflect ovarian failure in women with POF, whereas women with hypogonadotropic hypothalamic amenorrhea have normal levels of inhibins A and B and high levels of activin A.

Activins↗
PubMed1998

Selective deficits in reversal learning after neostriatum caudolaterale lesions in pigeons: possible behavioral equivalencies to the mammalian prefrontal system.

The neostriatum caudolaterale (NCL) of birds is thought to be equivalent to the mammalian prefrontal cortex (PFC) due to its dense dopaminergic innervation, its associative structure, and its importance for cognitive tasks which are known to be affected in mammals with prefrontal lesions. The aim of the present study was to analyze the functional importance of the NCL and its main thalamic afferent structure, the n. dorsolateralis posterior thalami (DLP), in reversal and go/no-go tasks, two behavioral procedures which are often used to assess mammalian prefrontal functions. Using a multiple regression analysis in which structure-specific lesion extents are correlated with different postoperative behavioral measures, the specific contribution of the relevant structures were differentiated from the neighbouring areas CDL (area corticoidea dorsolateralis) and NC (neostriatum caudale). The analyses showed a highly significant contribution of the NCL to reversal but not to go/no-go or to visual discrimination performance, while all other structures under analysis had no impact on any behavioral measure. These results underline the specific contribution of the pigeons' NCL on a subset of cognitive tasks which are known to be affected by prefrontal lesions in mammals.

Animals↗
PubMed1998

Glucagon-like peptide-2 inhibits centrally induced antral motility in pigs.

BACKGROUND: Glucagon-like peptide-2 is formed from proglucagon in the intestinal L-cells and is secreted postprandially in parallel with the insulinotropic hormone GLP-1 (glucagon-like peptide-1), which in addition acts to inhibit gastric motility (enterogastrone effect) by inhibiting central parasympathetic outflow. GLP-2 has no effect on the endocrine pancreas. We here tested the hypothesis that GLP-2 acts as an enterogastrone. METHODS: Fourteen anesthetized pigs with their splanchnic nerves cut were subjected to insulin hypoglycemia, and force transducers were sutured to the antrum to record motility. GLP-2 was infused intravenously in doses from 1 to 6 pmol/kg/min after the onset of antral motility in response to hypoglycemia. RESULTS: Insulin hypoglycemia invariably and greatly increased the frequency and amplitude of antral phasic contractions. Infusions of GLP-2 dose dependently (1-6 pmol/kg/min) inhibited antral motility. At 2 pmol/kg/min, resulting in plasma GLP-2 concentrations of 102.5+/-19 pmol/l (normal postprandial range, 30-82 pmol/l), the motility index was inhibited by 91%+/-14%. CONCLUSIONS: Both of the intestinal glucagon-like peptides may operate as hormonal transmitters of the ileal brake effect.

Animals↗
PubMed1998

Homeotic gene action in embryonic brain development of Drosophila.

Studies in vertebrates show that homeotic genes are involved in axial patterning and in specifying segmental identity of the embryonic hindbrain and spinal cord. To gain further insights into homeotic gene action during CNS development, we here characterize the role of the homeotic genes in embryonic brain development of Drosophila. We first use neuroanatomical techniques to map the entire anteroposterior order of homeotic gene expression in the Drosophila CNS, and demonstrate that this order is virtually identical in the CNS of Drosophila and mammals. We then carry out a genetic analysis of the labial gene in embryonic brain development. Our analysis shows that loss-of-function mutation and ubiquitous overexpression of labial results in ectopic expression of neighboring regulatory genes. Furthermore, this analysis demonstrates that mutational inactivation of labial results in regionalized axonal patterning defects which are due to both cell-autonomous and cell-nonautonomous effects. Thus, in the absence of labial, mutant cells are generated and positioned correctly in the brain, but these cells do not extend axons. Additionally, extending axons of neighboring wild-type neurons stop at the mutant domains or project ectopically, and defective commissural and longitudinal pathways result. Immunocytochemical analysis demonstrates that cells in the mutant domains do not express neuronal markers, indicating a complete lack of neuronal identity. An alternative glial identity is not adopted by these mutant cells. Comparable effects are seen in Deformed mutants but not in other homeotic gene mutants. Our findings demonstrate that the action of the homeotic genes labial and Deformed are required for neuronal differentiation in the developing brain of Drosophila.

Animals↗
PubMed1998

High levels of serum allopregnanolone in women with premature ovarian failure.

The endocrine characteristics of patients with premature ovarian failure (POF) have not been fully elucidated. The aim of the present study was to evaluate whether steroidogenic activity in women with POF is different with respect to fertile and postmenopausal subjects. In particular, circulating levels of allopregnanolone, a neuroactive steroid involved in modulation of reproductive function in rats, have been evaluated and correlated with serum levels of delta 4 precursor (dehydroepiandrosterone sulfate (DHEAS)), delta 5 intermediates (androstenedione, 17-hydroxyprogesterone (17-OHP), progesterone) and final products (estradiol and testosterone) of androgens. Levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and sex hormone binding globulin (SHBG) were also determined. In all cases specific radioimmunological assays were used. Women with POF showed statistically significantly lower concentrations of 17-OHP, androstenedione and testosterone when compared to fertile controls, while no differences were found between women with POF and postmenopausal women. Serum DHEAS levels were similar in POF patients and in fertile controls and higher with respect to postmenopausal women. Serum allopregnanolone levels were significantly higher in women with POF than in postmenopausal and in fertile women. A significant inverse correlation between allopregnanolone levels and menopausal age in patients with POF was observed while no significant correlation was found between allopregnanolone and progesterone, androstenedione, 17-OHP and testosterone levels. In conclusion, allopregnanolone is scarcely influenced by the reduction of ovarian and adrenal activity observed in POF.

Adult↗
PubMed1998

Impact of maternal body build characteristics on newborn size in two different European populations.

The association patterns between maternal anthropometric characteristics (stature, prepregnancy weight, prepregnancy body mass index, pregnancy weight gain) and newborn size (birth weight, length, head circumference) were tested with 10,240 single births taking place between 1985 and 1995 in Vienna, Austria, and 3,452 single births taking place between 1989 and 1995 in Westerstede-Ammerland (Friesland), northern Germany. Maternal size and newborn size differed highly significantly (p < 0.001) between the two genetically and socioeconomically different population groups. Furthermore, the incidence of macrosomia among newborns (birth weight greater than 4000 g) was extraordinarily high (17.9%) in the Frisian group from northern Germany. In both populations taller and heavier women with a higher weight gain during pregnancy gave birth to heavier offspring. Nevertheless, the pregnancy weight gain, which indicates environmental conditions of the mother, had only a minor impact on newborn size compared with stature and prepregnancy weight, which reflect the maternal genetic potential to a higher degree.

Austria↗
PubMed1997

Sensitivity of NMR internucleotide distances to B-DNA conformation: underlying mechanics.

Nuclear magnetic resonance (NMR) spectroscopy, combining correlated spectroscopy (COSY) coupling constant measurements with nuclear Overhauser effect spectroscopy (NOESY) interatomic distances, should make it possible to determine an averaged solution structure for DNA oligomers. However, even if such data could be obtained with high accuracy, it is not clear which structural parameters of DNA would be determined. Here, the relationships between measurable internucleotide distances and helical parameters are systematically studied through molecular modelling. Investigations are carried out using four representative sequences, (ACGT)n, (TCGA)n, (AGCT)n and (TGCA)n, composed of repeated tetranucleotides belonging to oligomers previously studied by NMR. Correlations between interatomic distances become evident and strong connections between distances and inter-base helical parameters are observed. Results imply that twist, roll, shift and slide values can be accurately determined from NMR data. Sequence independent mechanical coupling which link backbone and sugar conformations to helical twist are also described.

Base Sequence↗
PubMed1997

Post-burn reconstruction during growth and development.

Modern plastic and reconstructive surgery continues to significantly improve the functional and aesthetic post-burn sequelae in children. It has become a major factor in restoring mobility, aesthetic appearance, self-esteem, and quality of life. The entire spectrum of plastic reconstructive procedures should be available to offer the patient an optimal solution to his problems. Therefore, early interdisciplinary co-operation between pediatric and plastic surgeons is mandatory to plan and perform post-burn reconstruction in children and adolescents.

Adolescent↗
PubMed1997

Oral insulin for diabetes prevention in NOD mice: potentiation by enhancing Th2 cytokine expression in the gut through bacterial adjuvant.

Oral administration of insulin suppresses the development of diabetes in nonobese diabetic (NOD) mice and deviates the cytokine balance in the islets of Langerhans from a Th1 to a Th2 type cytokine pattern. However, the effect of oral insulin is limited and disease suppression is limited to a narrow dose range. Therefore we tried to improve the outcome of suboptimal insulin dosing by bacterial adjuvant. Mice treated with a suboptimal dose of oral insulin showed no change in diabetes incidence although a shift from Th1 towards Th2 cytokine expression occurred in inflamed islets. Significant suppression of diabetes development was only seen in NOD mice receiving both, insulin and the bacterial preparation OM-89 as adjuvant. OM-89 is a protein extract of Escherichia coli, with nonspecific immunostimulatory properties. Potentiation of the effect of oral insulin by the adjuvant was associated with upregulation of interleukin (IL)-4 Th2 cells in infiltrated islets and sustained local IL-2 gene expression. RT PCR analyses of cytokine expression in the gut showed a clear deviation to Th2 type reactivity and downregulation of inducible nitric oxide (NO) synthase (iNOS) expression by the bacterial adjuvant but not by oral insulin alone. Since macrophages are the primary target cells of adjuvant action we tested its effect on mouse macrophages in vitro. Treatment with OM-89 induced transient release of tumour necrosis factor alpha and nitrite but rendered macrophages refractory to restimulation by the potent macrophage activator lipopolysaccharide. In conclusion, the protective effect of oral insulin can be potentiated by pretreatment with the bacterial adjuvant OM-89. This effect correlates with enhanced Th2 cytokine and decreased iNOS gene expression in the gut, probably due to the downregulation of proinflammatory mediators by exposure to the adjuvant.

Adjuvants, Immunologic↗
PubMed1997

Early intragastric feeding of seriously burned and long-term ventilated patients: a review of 55 patients.

Aims of this retrospective study were: (1) to evaluate the feasibility of a protocol for early intragastric feeding: (2) to examine whether the caloric needs can be provided via the intragastric route within 72 h postburn; (3) to determine the influence of a delayed onset of feeding on the success of the feeding protocol; (4) to evaluate whether delayed feeding has any impact on morbidity and mortality. Fifty-five long-term ventilated patients were enrolled in the study. Their mean age was 37.6 years and mean total body surface area burned 44.2 per cent. The mean duration of ventilation amounted to 24.8 days. Intragastric tube feeding was initiated as early as possible after admission. Forty-five patients (81.8 per cent) could be fed successfully and their caloric needs were met within 72 h. In these patients the mean interval between burn injury and the initiation of tube feeding was 11.5 h. The mean interval was 32.4 h in the 10 patients, demonstrating failure of early intragastric feeding. Only four of the 48 patients who had enteral feeding within 18 h postburn failed to meet the caloric needs. The patients fed successfully showed a significantly decreased mortality. Early intragastric feeding after serious burns can be initiated successfully. A time interval of more than 18 h is unfavourable and significantly decreases the success rate.

Adolescent↗
PubMed1997

The impact of risk factors and pre-existing conditions on the mortality of burn patients and the precision of predictive admission-scoring systems.

Clinical experience has shown that concomitant diseases and risk factors have a significant influence on the patient's outcome. Since none of the currently available score systems consider the impact of concomitant diseases or risk factors on burn trauma mortality, the present study was planned to further evaluate the role of these factors. Four hundred and ninety-eight patients could be included in this retrospective analysis of prospectively collected data. Parameters documented were: sex, age, weight, height, laboratory data, TBSA, inhalation trauma (IHT), full thickness (3 degrees) burn and pre-existing conditions. Single-variable analysis (SVA), logistic regression and CART analysis were performed. The data confirm the role of age and TBSA as the strongest prognostic variables. Chronic alcohol abuse and smoking, IHT and pre-existing cardiac and neurologic conditions were also found to be significant. Borderline groups could be identified in the ABSI score (7-10), where the risk factors cause 'mortality-shifting'. It can be concluded that risk factors and pre-existing conditions have a significant impact on the prognosis of burn mortality and should be incorporated into further refinements of burn admission scores.

Adolescent↗
PubMed1997

The value of early enteral nutrition in the prophylaxis of stress ulceration in the severely burned patient.

A retrospective analysis of prospectively collected data was performed to compare the frequency of upper gastrointestinal bleeding (GIB) in seriously burned patients treated with either cimetidine and antacids or enteral nutrition for ulcer prophylaxis. Five hundred and twenty-six seriously burned patients admitted to the burn intensive care unit of the BG Trauma Centre Ludwigshafen during a 4-year period were included into the study. All patients admitted to the burn unit from 1989 to 1991 received i.v. cimetidine (400 mg q4) for ulcer prophylaxis. If the intragastric pH dropped below 3.5, gastric pH was titrated with antacids up to > or = 4 via nasogastric tube. During the second 2-year period (1992-1993) early enteral nutrition alone was regarded to be ulcer protective and no further interventions for ulcer prophylaxis were routinely performed. Signs of overt upper GIB were monitored and documented through the entire study period. The overall occurrence rate of upper GIB in the cimetidine/antacids (C/A) group (n = 253) was 8.3 per cent with six cases of serious bleeding in five patients (1.98 per cent). In the enteral nutrition (EN) group (n = 273) the overall incidence of GIB was 3.3 per cent with two cases of serious bleeding (0.73 per cent). There were no deaths directly related to ulcer haemorrhage. The difference in the overall frequency of overt GIB between the groups studied was statistically significant (< 0.05). In our experience, early enteral nutrition is effective in the prevention of stress haemorrhage in the upper gastrointestinal tract. Additional medicinal prophylaxis is not required in burn patients.

Administration, Oral↗
PubMed1997

Difference of LH and FSH secretory characteristics and degree of concordance between postmenopausal and aging women.

OBJECTIVE: Several neuroendocrine changes occur at menopause and the present study aimed to verify whether the episodic release and the degree of concordance of LH and FSH differs between early and late postmenopausal women. METHODS: Postmenopausal (n = 32) women were enrolled and subdivided in two groups according to the menopausal age: group A (n = 22), patients with more than 2 but less than 5 years from the occurrence of menopause; group B (n = 10), patients with more than 15 years from the occurrence of menopause. All subjects underwent a pulsatility study (4 h, sampling every 10 min) to assess LH and FSH secretory characteristics and their degree of concordance. RESULTS: Mean +/- S.E.M. LH and FSH plasma levels were lower in older women than in postmenopausal women (P < 0.01). The secretory pattern was pulsatile for both LH and FSH and their pulse amplitudes were lower in aged women (P < 0.01). No significant difference was observed in terms of pulse frequency between the two groups. LH and FSH pulses were co-secreted in early postmenopausal women while such a concordance was lost in older women. CONCLUSIONS: Late postmenopause is characterized by the reduction of the amplitude of gonadotropin pulses in comparison to women in early postmenopause, reflecting changes of both GnRH secretion and/or pituitary responsiveness to GnRH. The age-related loss of concordance between LH and FSH pulses discloses the existence of a hidden FSH stimulating system, which drives FSH episodic release independently and more promptly than GnRH.

Aging↗