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Biomedical subjects

B Hartmann

Publications and source records attributed to B Hartmann.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1997

Raynaud's phenomenon in vibration syndrome: the impact of cold feet on skin temperature and vasomotion of the hand after immersion in cold water.

Patients with vibration syndrome, suffering from Raynaud's phenomenon, are sensitive to cold. Rewarming time, after local cooling, is delayed. The present study evaluated whether rewarming of the hand after cooling is influenced by the temperature of the feet. In five Japanese patients (former forest workers) with vibration syndrome, suffering from Raynaud's phenomenon, and in five healthy controls, temperature changes of the hand after cooling were registered under the two test situations (on different days) with the feet immersed in water of 35 degrees C or 20 degrees C, respectively. In both patients and controls (in both groups, in four of five cases) rewarming of the hand after cooling was faster when the feet were immersed in cold water, compared with when the feet were immersed in warm water. In this test situation, the systemic thermoregulative counterreaction appears to be more important for rewarming of the hand after cooling than a possible synchronous passive reaction accompanying warming of the feet. A deliberate training of the systemic counterreaction may prove beneficial for patients with Raynaud's phenomenon.

Adult↗
PubMed1997

Population control I: Birth of an ideology.

Population control, as a major international development strategy, is a relatively recent phenomenon. However, its origins reach back to social currents in the 19th and early 20th centuries, culminating in an organized birth control movement in Europe and the United States. The conflicts and contradictions in that movement's history presage many of today's debates over population policy and women's rights. Eugenics had a deep influence on the U.S. birth control movement in the first half of the 20th century. After World War II private agencies and foundations played an important role in legitimizing population control as a way to secure Western control over Third World resources and stem political instability. In the late 1960s the U.S. government became a major funder of population control programs overseas and built multilateral support through establishment of the U.N. Fund for Population Activities. At the 1974 World Population Conference, Third World governments challenged the primacy of population control. While their critique led population agencies to change their strategies, population control remained a central component of international development and national security policies in the United States.

Eugenics↗
PubMed1997

Population control II: The population establishment today.

Although population assistance represents a relatively small share of official development assistance, it influences many other aspects of development planning. The organizations that comprise the population establishment have a common purpose--the reduction of population growth in the Third World--but they are not homogeneous and sometimes have conflicting goals and strategies. National governments, multilateral agencies, nongovernmental organizations, foundations, academic centers, and pressure groups all contribute to creating and sustaining what has become a virtual population control industry. Through scholarships, travel grants, awards, and favorable publicity, Third World elites have been encouraged to join the population establishment. The World Bank, the U.S. Agency for International Development, and the U.N. Fund for Population Activities have pursued explicit strategies for pressuring Third World governments to design and implement population policies, most recently in Africa.

Coercion↗
PubMed1997

[Significance of the circadian fluctuation of estradiol, somatotropin, IGF I, prolactin, cortisol and DHEA-S for the body-shape of pre- and postmenopausal women].

With 23 postmenopausal and 33 premenopausal females the interactions between circadianic secretion patterns of estradiol, growth hormone, IGF I, prolactin, DHEA-S as well as cortisol and the amount and distribution of subcutaneous body fat, estimated by using 10 absolute body measures and 10 anthropometric indices were tested. Premenopausal and postmenopausal women differed regarding the secretion patterns of estradiol and growth hormone significantly from each other. Furthermore it turned out, that the daily secretion rate, estimated by using the area under the curve, of growth hormone and estradiol correlated significantly with the amount and the distribution of body fat. In both proband groups more corpulent women had lower growth hormone levels and higher estradiol levels. The age dependent reduction of growth hormone secretion may be co-responsible for the general weight gain with increasing age. The reduced estrogen secretion however, seems to be the major determinant of the expression of a more masculine type of fat distribution during climacteric and after the menopause.

Adipose Tissue↗
PubMed1996

Solution structure of the CpG containing d(CTTCGAAG)2 oligonucleotide: NMR data and energy calculations are compatible with a BI/BII equilibrium at CpG.

We report the analysis of the solution structure of the DNA duplex d(CTTCGAAG)2 compared to that of d(CATCGATG)2, the two oligonucleotides being related by the permutation of residues 2 and 7. An earlier study has demonstrated the malleability of CpG in the tetrad TCGA of d(CATCGATG)2 [Lefebvre et al. (1995) Biochemistry 34, 12019-12028]. Conformations of d(CTTCGAAG)2 were evaluated by (a) two-dimensional NMR, including proton and phosphorus experiments, (b) adiabatic mapping of the conformational space, (c) restrained molecular mechanics undertaken with sugar phase angle, epsilon-zeta difference angle, and NOE distances as input, and (d) back-calculation-refinement against NOE spectra at various mixing times. d(CTTCGAAG)2 like d(CATCGATG)2 exhibits a B-DNA conformation. However, significant differences are noted between the two oligonucleotides, extending up to the central CpG step, although this step resides in the same TCGA tetrad in both sequences. In structures obtained with refined NMR data, CpG adopts, for instance, a greater twist and a higher guanine phase within d(CTTCGAAG)2 compared to d(CATCGATG)2. In the former oligonucleotide, the structure of CpG resembles strikingly that found in the ACGT tetrad of the cAMP responsive element [Mauffret et al. (1992) J. Mol. Biol. 227, 852-875]. Moreover, two conformers with CpG either in the BII state (epsilon, zeta = g-, t) or in the BI state (epsilon, zeta = t, g-) are found equally stable for d(CTTCGAAG)2. The energy barrier from BI to BII comes to only 5.7 kcal/mol, and the path of the transition is very short. When calculations on d(CTTCGAAG)2 are performed taking the BI/BII equilibrium into account, the agreement with both the 1H and 31P data is found better than in the case with a single conformation taken alone. The BI/BII equilibrium may also occur in d(CATCGATG)2, but the amount of BII conformer is now found weaker compared to its analogue. The ability of the CpG phosphate groups to adopt the BII conformation could provide a satisfying explanation for the high mutation rates observed at these sites.

CpG Islands↗
PubMed1996

Interleukin-12 gene-expression of macrophages is regulated by nitric oxide.

Interleukin-12 is a heterodimeric cytokine, mainly produced by macrophages. In our present study we demonstrate that interleukin-12 expression is regulated by nitric oxide. Incubation of the macrophage cell line IC 21 with interferon-gamma gave rise to both interleukin-12 p40 mRNA and nitric oxide production. The concurrent addition of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine inhibited nitrite production and in parallel completely suppressed interleukin-12 p40 mRNA formation. This indicated that endogenous nitric oxide synthase activity was required for IL-12 p40 gene expression. Exposure of the cells towards the nitric oxide generating compounds nitroprusside or S-nitroso-N-acetyl-penicillamine induced interleukin-12 p40 mRNA. Maximal mRNA levels were induced with nitric oxide donors at 1 microM concentration. We conclude that nitric oxide may exert an autoregulatory and paracrine control of interleukin-12 gene expression.

Animals↗
PubMed1996

The Drosophila tumor suppressor gene, dlg, is involved in structural plasticity at a glutamatergic synapse.

BACKGROUND: Synaptic contacts between neurons and their targets are dynamic entities that can change depending on developmental and functional states of the pre- and postsynaptic cell. However, the molecular factors involved in this plasticity have remained largely unknown. We have demonstrated previously that the Drosophila tumor suppressor gene, discs-large (dlg), is expressed at neuromuscular synapses, and is required for normal synapse structure. A family of dlg homologues is also expressed at mammalian synapses, where they interact with the N-methyl-D-aspartate receptor and ion channels. Here, we provide the first demonstration of the involvement of dlg in structural synaptic plasticity during postsynaptic target growth. RESULTS: We used a temperature-sensitive dlg allele to demonstrate that there are two stages, late embryogenesis and larval stages, at which dlg is necessary for normal formation of synapses. These stages are coincident with dynamic DLG expression at presynaptic sites in the late embryo, and at postsynaptic regions in the larva. Ultrastructural and confocal analyses reveal that Drosophila neuromuscular junctions undergo a dramatic expansion of the postsynaptic apparatus, which is paralleled by target muscle growth. We show that this process of postsynaptic expansion is partially blocked in dlg mutants. CONCLUSIONS: Our results demonstrate that dlg is required during synapse maturation. We show that dlg is involved in the determination of postsynaptic size during target muscle growth. Because motoneuron targets in the larva are continuously growing, synaptic contacts are structurally plastic, undergoing continuous expansion. We conclude that dlg plays an important role in this form of structural synaptic plasticity.

Animals↗
PubMed1996

Effects of hormonal replacement therapy on plasma sex hormone-binding globulin, androgen and insulin-like growth factor-1 levels in postmenopausal women.

Plasma sex hormone-binding globulin (SHBG) levels are important in the regulation of plasma free and albumin-bound androgens and estrogens. In postmenopausal women associated to the decrease of estrogen production, a decrease of plasma SHBG levels occurs. Hormone replacement therapy (HRT) in postmenopausal women modulates plasma SHBG levels, in relationship with the different regimens and routes of administration. The present study aimed to compare the effect of different HRT on plasma SHBG levels in relationship with the changes of plasma androgen [dehydroepiandrosterone sulphate (DHEAS), testosterone (T), androstenedione (A)] and insulin-like growth factor-1 (IGF-1) levels. In a retrospective study 443 postmenopausal women were studied and divided into 2 groups. The group 1 (n = 170) was subdivided in 4 groups of women as follows: A) treated with transdermal 17-beta estradiol + medroxyprogesterone acetate, B) treated with oral conjugated estrogens, C) treated with sequential HRT (estradiol valerate (EV) + norgestrel), and D) treated with a combined HRT (micronized estradiol (E2) + noretisterone acetate). Women of group 2 (n = 273) did not receive HRT and served as controls. All groups of women treated with different HRT showed plasma estradiol levels significantly higher than controls (p < 0.01), showing the highest values in women treated with oral HRT. Plasma SHBG levels were not significantly different between patients treated with transdermal 17-beta estradiol + medroxyprogesterone acetate and controls. On the other hand, all the groups of patients treated with oral conjugated estrogen with or without progestagens showed plasma SHBG levels significantly higher than controls (p < 0.01). Plasma SHBG levels were higher in the group treated with estrogen alone than in groups of women treated with sequential or combined HRT. Plasma DHEAS, T and A levels in patients treated with different HRT regimens were in the same range of levels as control women. Plasma IGF-1 levels were not significantly affected by the various HRT regimens and remained in the same range as controls. In conclusion, plasma SHBG levels increase following oral HRT while are not affected by transdermal HRT. Plasma IGF-1 and androgen levels are not influenced from oral or transdermal HRT.

Adult↗
PubMed1996

Decreased sexual interest and its relationship to body build in postmenopausal women.

OBJECTIVES: The relationship between body build, androgen levels and changes in sexual interest after menopause was investigated in 171 postmenopausal women from Vienna, Austria. METHODS: All women were interviewed using a structured questionnaire. Body build was determined by employing five absolute body dimensions and four anthropometric indices. RESULTS: Body weight, as well as the amount of subcutaneous centripetal fat (such as in the chest, waist and hip region), were statistically significantly related to the degree of reduced sexual interest. Corpulent and heavy women suffered far more frequently from a severe decrease in sexual interest after menopause. Statistically significant associations between androgen levels and decrease in sexual interest could not be demonstrated. CONCLUSIONS: Reduced sexual interest is associated with a kind of body type not corresponding to the culture-specific beauty ideals of our society, first of all evident in women whose menopause occurred relatively early.

Adult↗
PubMed1996

Regulation of synapse structure and function by the Drosophila tumor suppressor gene dlg.

Mutations of the tumor suppressor gene discs-large (dlg) lead to postsynaptic structural defects. Here, we report that mutations in dlg also result in larger synaptic currents at fly neuromuscular junctions. By selectively targeting DLG protein to either muscles or motorneurons using Gal-4 enhancer trap lines, we were able to rescue substantially the reduced postsynaptic structure in mutants. Rescue of the physiological defect was accomplished by presynaptic, but not postsynaptic targeting, consistent with our finding that miniature excitatory junctional currents were not changed in dlg mutants. These results suggest that DLG functions in the regulation of neurotransmitter release and postsynaptic structure. We propose that DLG is an integral part of a mechanism by which changes in both neurotransmitter release and synapse structure are accomplished during development and plasticity.

Animals↗