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Biomedical subjects

B Hartmann

Publications and source records attributed to B Hartmann.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1996

Metabolic activation of islet cells improves resistance against oxygen radicals or streptozocin, but not nitric oxide.

In the present study we investigated the effect of metabolic activation on the susceptibility of isolated rat pancreatic islet cells to the alkylating beta-cell toxin streptozocin (SZ), reactive oxygen intermediates (ROI), and nitric oxide (NO). The latter two represent physiologically occurring mediators involved in the autoimmune destruction of islet cells. ROI were generated by the enzyme xanthine oxidase, and NO was released from sodium nitroprusside. During 18 h of culture at a physiological glucose concentration (5 mmol/L), 75% of the islet cells were lysed by SZ, 81% by ROI, and 74% by NO, as determined by the trypan blue exclusion assay. Increasing concentrations of glucose or the nonnutrient stimulators theophylline and glibenclamide dose-dependently reduced SZ- and ROI-mediated islet cell lysis. In the presence of 29 mmol/L glucose, 5.5 mmol/L theophylline, or 10 micrograms/mL glibenclamide, SZ-induced lysis was reduced to 15%, 22%, or 15%, and ROI-induced lysis was reduced to 20%, 34%, or 15%, respectively. In contrast, stimulation by glucose, theophylline, or glibenclamide did not improve resistance against NO. The protection against SZ and ROI was associated with preserved mitochondrial activity, as determined by the ability of the islet cells to convert the tetrazolium salt 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide into its formazan. Elevation of the glucose concentration from 5.5 to 29 mmol/L increased the residual mitochondrial activity from 45% to 80% in SZ-exposed islet cells and from 21% to 78% in ROI-exposed cells. Conversely, the lack of protection against NO correlated with no preservation of mitochondrial activity in the presence of high concentrations of glucose, theophylline, or glibenclamide. In conclusion, our results show that metabolic stress does not render islet cells more susceptible to inflammatory insults in vitro. Rather, an increased mitochondrial energy supply improves the resistance against SZ and ROI, whereas the toxicity of NO was independent of islet cell activity.

Animals↗
PubMed1996

Experience with the modified Meek technique.

In 1958 Meek described the so called Meek-Wall dermatome to cut postage stamp skin grafts. This method was eclipsed by the introduction of mesh skin grafts. In 1993 Kreis and colleagues reintroduced a modified Meek technique using a dermatome running on compressed air. This technique has been used in our burn unit since August 1994. The aim of this paper is to compare the modified Meek technique with the mesh graft technique. Within a period of 20 months 41 patients were grafted using the modified Meek technique. The mean TBSAB was 54.4% with 50.0% full thickness burns. All patients were excised early. The expansion ratio was 1:4 and 1:6. In 20 patients the Meek technique was used exclusively for grafting of the trunk and the extremities with the exception of face, neck and hands. In 3 patients with a mean TBSAB of 68.3% a combination of postage stamp autologous skin grafts and cultured epithelial autografts (CEA) was applied. Compared with the mesh graft technique the Meek technique showed the following advantages: 1. The Meek method provides the true expansion ratio. 2. Small graft remnants can be utilized. 3. Grafting of full thickness burns up to 70 to 75% TBSAB becomes possible with one harvest of the donor sites. 4. The reliability of graft take is equal or better. 5. Epithelialization is achieved within 3 to 4 weeks depending on the expansion ratio. 6. The combination of widely expanded postage stamp split thickness grafts and CEA provides an excellent take rate and durable wound closure within a short time and avoids the problems associated with the engraftment of CEA on fascia. The method is simple but more demanding than the mesh technique. Compared with the mesh graft technique the preparation of Meek grafts is more time consuming and requires more staff than the Mesh technique. The cost of materials is higher. In our experience complete coverage of the Meek grafts with an overlay of meshed allografts after removal of the gauze as recommended by Kreis is not necessary using the 1:4 expansion ratio. Greater expansion ratios necessitate an overlay with meshed allografts. Regarding the scar formation no significant differences were observed compared with the mesh graft technique. In conclusion the modified Meek technique is reliable and simple to perform. This technique provides a sufficient expansion ratio enabling to graft patients with burns up to 75% TBSA with only one harvest of donor sides and without the necessity of CEA. In our opinion the Meek technique is reliable and simple to perform. This technique provides a sufficient expansion ratio enabling to graft patients with burns up to 75% TBSA with only one harvest of donor sides and without the necessity of CEA. In our opinion the Meek technique is advantageous in patients with burns greater than 45% TBSAB. In smaller burns mesh grafts should be used because of lower material cost and staff requirements. Especially in extensively burned patients the Meek technique may be cost effective avoiding the need of CEA.

Adolescent↗
PubMed1996

Serum levels of sex hormones, thyroid hormones, growth hormone, IGF I, and cortisol and their relations to body fat distribution in healthy women dependent on their menopausal status.

The relations between 10 anthropometric variables describing the amount of adipose tissue and the serum levels of thyroxine, triiodothyronin, thyroid stimulating hormone, estradiol, progesterone, 17-hydroxyprogesterone, prolactin, luteinizing hormone, follicle stimulating hormone, DHEA-S, androstendion, testosterone, sex hormone binding globulin, growth hormone, IGF I as well as cortisol were investigated in 39 premenopausal and 38 postmenopausal women. Several statistically significant correlations between hormonal parameters and the amount and the distribution of subcutaneous fat tissue were found for the premenopausal group. The postmenopausal probands, however, showed fewer statistically significant connections between the two trait systems. The correlation patterns in both proband groups resembled each other. Only with regard to the gonadotropines (LH and FSH) a difference in the algebraic sign of the correlation coefficients can be observed for pre- and postmenopausal probands. The multiple regression analysis corroborated the hypothesis that hormonal parameters are responsible for somatic changes after menopause.

Adipose Tissue↗
PubMed1995

Structural behavior of the CpG step in two related oligonucleotides reflects its malleability in solution.

We report on the determination of the solution structure of two sequence-related oligonucleotides, d(GTACGTAC)2 and d(CATCGATG)2. Results have been obtained by using a combined approach of (a) two-dimensional NMR, including proton and phosphorus experiments, (b) restrained molecular mechanics performed with sugar phase angle, backbone epsilon angle, and NOE distances as input, and (c) back-calculation refinements against the NOE spectra at various mixing times. The two oligonucleotides adopt the B-DNA structure with, however, noticeable differences centered on their core sequence and especially the CpG step. Due to the permutation of its flanking residues, the CpG step modifies its twist values and backbone epsilon value; globally, the CpG step appears more flexible within the tetranucleotide TCGA than ACGT. The solution structure of d(GTACGTAC)2 differs from the previously reported X-ray structure, which was found to be A-form throughout [Takusagawa, F. (1990) J. Biomol. NMR 3, 547-568]. On the other hand, in the X-ray structure of d(CCAACGTTGG)2 [Privé et al. (1991) J. Mol. Biol. 217, 177-199] the structure of the ACGT sequence is similar to that found in solution d(GTACGTAC)2. Similarly, the central TCGA tetranucleotide of d(CATCGATG)2 presents a solution structure analogous to that observed on the X-ray structures of both d(CGATCGATCG)2 [Grzeskowiak, et al. (1991) J. Biol. Chem. 266, 8861-8883] and d(CGATCGmeATCG)2 [Baïkalov, et al. (1993) J. Mol. Biol. 231, 768-784]. At the end we discuss the possible biological significance of the particular structures exhibited by the ACGT and TCGA tetranucleotides.

Base Sequence↗
PubMed1995

Solution structure of a homopyrimidine: homopurine dodecamer encoded by the HIV-1 envelope gene: NMR and molecular simulation studies.

The solution structure of the nonpalindromic dodecanucleotide homopyrimidine:homopurine, d(5'-TTTCTCCTTTCT):d(5'-AGAAAGGAGAAA), was determined by two-dimensional nuclear magnetic resonance spectroscopy combined with molecular simulation. The dodecamer sequence studied was found within the HIV-1 envelope sequence and had all four Gs substituted by A in two hypermutants. A set of low-energy B-DNA conformations satisfying the quantitative NOE data were obtained. These highly related structure had neither peculiar helical parameters for the base pairs nor axis curvature. Analysis of the dihedral angles (epsilon-zeta) suggests that the A stretches flanking the GpA dinucleotides were more flexible.

Base Sequence↗
PubMed1995

Hypothalamic-pituitary-gonadal axis in depressed premenopausal women: elevated blood testosterone concentrations compared to normal controls.

To assess the function of the hypothalamic-pituitary-gonadal (HPG) axis in major depression, a multihormonal study was carried out in 20 depressed premenopausal women. Serum concentrations of LH, FSH, estradiol, progesterone, testosterone, and GnRH-stimulated LH and FSH were measured before initiation of treatment (on the first day after menstruation) and during clomipramine treatment (same time one menstrual cycle later). Significantly higher blood concentrations of testosterone were found in untreated patients compared to normal controls. Furthermore, there was a significant negative correlation between Hamilton depression scores and estradiol concentrations of patients. The efficacy of clomipramine treatment was not related to hormonal parameters.

Adult↗
PubMed1995

Effects of hormone replacement therapy on growth hormone secretion patterns in correlation to somatometric parameters in healthy postmenopausal women.

OBJECTIVES: The aim of the present study was to investigate the influence of a continuous estrogen, cyclic progesterone replacement therapy on the secretion of growth hormone (GH) and IGF I as well as of somatometric-GH correlation patterns. METHODS: The study included 23 healthy postmenopausal women. Of the proband group 13 randomly selected women were treated with orally applicated 2 mg estradiol-valerat (E2V) and 10 mg dydrogesterone for 10 months. Ten women did not receive any hormonal treatment during this time. After 10 months all probands were reexamined and their GH and IGF I secretion, as well as their somatometric-hormonal correlation patterns, compared with those of a fertile control group. RESULTS: It could be shown, that in postmenopausal women a 10-month oral hormone replacement therapy led to a significant increase of GH- and IGF I levels, however, the treated postmenopausal women did not reach the levels of the fertile controls. Those women who did not receive any hormonal treatment and the postmenopausal women before HRT showed nearly identical GH- and IGF I levels as well as somatometric-GH correlation patterns. CONCLUSIONS: The results of the present paper indicate a marked influence of estrogens on GH and IGF I secretion. Furthermore, hormonal replacement therapy (HRT) may influence somatometric GH correlation patterns too.

Adult↗
PubMed1995

Characterization of an 80-kD membrane glycoprotein (gp80) of human keratinocytes: a marker for commitment to terminal differentiation in vivo and in vitro.

We have characterized an 80-kD cell-surface glycoprotein (gp80) identified by monoclonal antibody BT 15, the expression of which is closely associated with a commitment to terminal squamous or follicular differentiation of keratinocytes in normal adult and fetal human epidermis. Maximum expression was found in the suprabasal layers, but basal cells located at the epidermal sulci were also clearly positive, in contrast to the virtually negative basal cells at the epidermal ridges. This protein was also present in benign hyperproliferative disorders of the epidermis (i.e., common warts, keratoacanthoma, psoriasis, and seborrhoic keratoses) with monoclonal antibody BT 15 preferentially staining suprabasal cells and some basal cells at the epidermal sulci. Gp80 was completely lacking in most basal cell carcinomas; the only exceptions were two cases of partially cornifying tumors that were strongly stained around keratotic pearls. In squamous cell carcinomas, gp80 was expressed in keratinized areas of the tumors. In organotypic keratinocyte cultures that resemble the in vivo situation, gp80 was strongly expressed in the suprabasal layers. However, unlike known markers for terminal differentiation, gp80 was weakly expressed by basal cells. Synthesis rates of gp80 were high in keratinocyte cell suspensions freshly prepared from skin, and decreased in primary cultures and first and second subcultures (ratio 10:4:2:1). Elevated concentrations of the Ca++ that increased stratification of cultured keratinocytes resulted in a two- to threefold increase of gp80 synthesis. GP80 was not synthesized at detectable levels by the immortal keratinocyte cell line HaCaT; however, it was expressed in HaCaT cultures treated with mitomycin C, indicating an association with cessation of growth. Pulse-chase experiments revealed that gp80 is synthesized from a 55-kD precursor molecule, the maturation of which was prevented by treating cells with tunicamycin. Glycosidase digestion of BT 15 immunoprecipitates from untreated cells indicated that the predominant post-translational modification of the protein is N-linked glycosylation. Our data indicate that gp80 is a glycoprotein that is expressed by growth-arrested human keratinocytes or as part of the terminal differentiation program.

Biomarkers↗
PubMed1994

Fusidic acid suppresses nitric oxide toxicity in pancreatic islet cells.

Earlier preclinical and clinical trials indicate that fusidic acid, a triterpenoid compound originally described as an antimicrobial drug may protect islet beta cells from destruction in type I (insulin-dependent) diabetes mellitus. Since nitric oxide appears to be an important mediator of inflammatory islet cell death we analyzed whether fusidic acid interferes with nitric oxide production or action. We report here that fusidic acid dose-dependently inhibits lysis of isolated islet cells by activated macrophages, a process mediated by nitric oxide. In the presence of 100 microM fusidic acid macrophage-mediated islet cell lysis was reduced from 52.5 to 1.7% (P < 0.001). Fusidic acid only slightly affected macrophage function and did not inhibit the release of nitric oxide. We therefore tested whether fusidic acid suppresses nitric oxide toxicity in target cells. Isolated islet cells were exposed to the nitric oxide donor nitroprusside which led to DNA strand breaks and plasma membrane lysis. DNA strand breaks were reduced from 54.6 to 34.9% (P < 0.001) in the presence of 100 microM fusidic acid and cell lysis was reduced from 60.1 to 27.5% with 100 microM (P < 0.001). In the presence of 500 microM fusidic acid DNA strand breaks and cell lysis were reduced further to 27.1 and 10.7%, respectively (P < 0.001). No protection by fusidic acid was observed when cells were exposed to oxygen radicals or the alkylating beta cell toxin streptozotocin. The suppression of nitric oxide toxicity by fusidic acid was not due to its known inhibitory action on protein biosynthesis and thus represents a hitherto unknown activity of this drug.

Animals↗
PubMed1994

Proglucagon processing in porcine and human pancreas.

In the pancreas proglucagon (PG), a peptide precursor of 160 amino acids is cleaved to produce glucagon and a 30-amino acid N-terminal flanking peptide, but the fate of the C-terminal flanking peptide (99 amino acids) is incompletely known. We subjected acid ethanol extracts of human and porcine pancreases to gel filtration and analyzed the fractions with specific radioimmunoassays for the following regions of proglucagon: PG 62-69, PG 72-81, PG 78-87, PG 98-107 amide, PG 126-134, and PG 149-158. Based on these assays and successive purifications by high performance liquid chromatography we isolated and purified to homogeneity three porcine peptides which were subjected to mass spectrometry and sequencing. One peptide was PG 64-69. The second was PG 72-108, as determined by mass spectrometry, N-terminal amino acid sequencing, and specific radioimmunoassays. The third had a molecular size of approximately 10,000, an N-terminal sequence corresponding to PG 72-81, and a C-terminal sequence terminating at PG 158 (specific radioimmunoassay). A similar peptide with an identical N-terminal sequence, a C-terminal sequence corresponding to PG 146-158, and a molecular mass of 9969 (theoretical mass for human PG 72-158 = 9971) was isolated from human pancreas together with small amounts of a peptide corresponding to PG 72-107 amide. Thus, the pancreatic processing of the C-terminal flanking peptide in proglucagon includes the formation of equimolar (to glucagon) amounts of PG 64-69 and PG 72-158 (major proglucagon fragment) and smaller amounts of N-terminally extended glucagon-like peptide-1 (GLP-1) (PG 72-108 in pigs and PG 72-107 amide in humans).

Amino Acid Sequence↗
PubMed1994

Nitric oxide toxicity in islet cells involves poly(ADP-ribose) polymerase activation and concomitant NAD+ depletion.

Previous studies have shown that DNA strand breaks are an early consequence of nitric oxide toxicity in pancreatic islet cells. We show here that exposure of islet cells to chemical NO donors causes the formation of ADP-ribose polymers in cell nuclei, with concomitant depletion of intracellular NAD+. Islet cell lysis was largely prevented by the ADP-ribosylation inhibitors nicotinamide, 3-aminobenzamide, and 4-amino-1,8-naphthalimide, the latter being a potent new-generation compound with high selectivity for poly(ADP-ribosyl)-ation. These findings indicate a key role of poly(ADP-ribose) polymerase activation in NO toxicity in islet cells.

1-Naphthylamine↗
PubMed1994

Depletion of total cysteine, glutathione, and homocysteine in plasma by ifosfamide/mesna therapy.

The sulfhydryl status of cells, particularly the intracellular concentration of glutathione, is a critical determinant of the response of tumor and normal cells to cytostatic drugs. Recent data indicate that the administration of mercaptoethane sulfonate (mesna), which is often combined with ifosfamide, markedly decreases the circulating concentration of total cysteine and could thereby influence the response of the organism to the cytotoxic effects of chemotherapy. The aim of the present study was to assess the effects of the combination of ifosfamide/mesna on sulfhydryl and disulfide homeostasis in tumor patients. Ifosfamide was infused into 14 patients with advanced sarcoma for 5 days at a dose of 2.4-3.2 g/m2 per day together with mesna. The plasma concentrations of total mesna, cysteine, glutathione, and homocysteine were measured before and on days 1 and 6 of the first course of ifosfamide/mesna therapy and prior to the next course of chemotherapy, and the urinary excretion of cysteine and mesna was monitored daily using a high-performance liquid chromatography (HPLC) method. Ifosfamide/mesna resulted in a marked depletion of circulating total cysteine, i.e., cysteine, cystine, and cysteine mixed disulfides [from 245 +/- 36 to 50 +/- 14 nmol/ml (mean +/- 95% CI) on day 6], total glutathione (from 6.9 +/- 1.1 to 2.5 +/- 1.1 nmol/ml), and total homocysteine (from 12.3 +/- 2.1 to 1.4 +/- 1.1 nmol/ml). The values returned to baseline levels prior to the next course of chemotherapy. The urinary excretion of cysteine increased significantly from 0.28 to 1.82 mmol/day on the 1st day, whereupon it returned toward baseline. An average of 62% +/- 6% of the delivered dose of mesna was recovered in urine. The combination of ifosfamide/mesna results in depletion of circulating total cysteine, glutathione, and homocysteine. This marked derangement of sulfhydryl and disulfide homeostasis could modulate the efficacy and toxicity of ifosfamide/mesna therapy.

Adult↗
PubMed1994

Modelling DNA conformational mechanics.

Using a modelling technique specifically adapted to DNA helices, we have systematically studied the impact of base sequence on the geometry of the double helix. The results obtained show that each repetitive base sequence leads to several stable conformations belonging to the B-DNA family. These conformational sub-states generally have similar stabilities, but often differ considerably in terms of their helical and backbone parameters. Each sub-state can be characterised by the puckering of its sugar rings. Surface energy mapping and combinatorial search techniques are used to further understand the DNA conformational hypersurface and to extend our study from dinucleotide repeats to tetranucleotide sequences. The resulting structural database should be useful for predicting the properties of longer and more irregular base sequences and thus should contribute to understanding how DNA target sites are recognised.

Base Sequence↗
PubMed1994

The role of prolactin in the menopause.

Within a study on menopausal discomforts, 2322 women were seen for the first time at the Outpatients Department for Climacteric Disturbances and Prophylaxis of Osteoporosis at our clinic. Amongst routine hormonal examination we measured prolactin levels. We found hyperprolactinemia in 23 women. Furthermore, in 224 women who initially had normal hPRL values, an estrogen-gestagen replacement therapy was administered and within this we found a significant increase of the prolactin levels (P < 0.005). The role of prolactin in the climacteric period as well as the mechanism of the estrogen effect upon prolactin secretion are subjects of discussion.

Climacteric↗