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Biomedical subjects

M Heinrich

Publications and source records attributed to M Heinrich.

At least 37 records · Page 2Linked to original sources
PubMed2004

Partial deletions in the AZFc region of the Y chromosome occur in men with impaired as well as normal spermatogenesis.

BACKGROUND: Partial deletions of the AZFc region of the Y chromosome were reported to be a significant risk factor for oligo-/azoospermia. In this study, we assessed the occurrence and frequency of partial AZFc microdeletions in patients with spermatogenic failure and in controls with normal spermatogenesis. METHODS: In a retrospective study design, gr/gr, b1/b3 and b2/b3 deletions were analysed by multiplex PCR in 170 men with normal spermatogenesis and 348 men with non-obstructive oligo-/azoospermia. RESULTS: gr/gr deletions were found in 14 men with oligozoospermia or azoospermia (4.0%) and in three normozoospermic men (1.8%) (NS). b1/b3 deletions were found both in controls (n=1) and in patients (n=1). b2/b3 deletions were significantly more frequent in the normozoospermic (five out of 170) than in the oligo-/azoospermic men (two out of 348). Three novel partial AZFc deletion patterns were found in four oligo-/azoospermic men. No correlation with semen or other clinical parameters was found. CONCLUSIONS: The frequency of gr/gr deletions is not significantly increased in men with oligo-/azoospermia, indicating that they are not sufficient per se to cause spermatogenetic impairment and infertility. b1/b3 and b2/b3 deletions are probably irrelevant for spermatogenesis. Novel deletion patterns found exclusively in infertile men suggest that other, still unexplored partial deletions might contribute to spermatogenic failure.

Case-Control Studies↗
PubMed2004

Self-assembly of poly(ethylene oxide)-b-poly(epsilon-caprolactone) copolymers in aqueous solution.

The associative behavior of monodisperse diblock copolymers consisting of a hydrophilic poly(ethylene oxide) block and a hydrophobic poly(epsilon-caprolactone) or poly(gamma-methyl-epsilon-caprolactone) block has been studied in aqueous solution. Copolymers have been directly dissolved in water. The solution properties have been studied by surface tension, in relation to mesoscopic analyses by NMR (self-diffusion coefficients), transmission electron microscopy, and small-angle neutron and X-ray scattering. The experimental results suggest that micellization occurs at low concentration (approximately 0.002 wt %) and results in a mixture of unimers and spherical micelles that exchange slowly. The radius of the micelles has been measured (ca. 11 nm), and the micellar substructure has been extracted from the fitting of the SANS data with two analytical models. The core radius and the aggregation number change with the hydrophobic block length according to scaling laws as reported in the scientific literature. The poly(ethylene oxide) blocks are in a moderately extended conformation in the corona, which corresponds to about 25% of the completely extended chain. No significant modification is observed when poly(gamma-methyl-epsilon-caprolactone) replaces poly(epsilon-caprolactone) in the diblocks.

Journal Article↗
PubMed2004

Spin dynamics and charge order in beta-Na1/3V2O5.

We present detailed electron-spin resonance investigations on single crystals of the one-dimensional vanadium-oxide bronze beta-Na(1/3)V2O5. From the angular dependence of the g value it can be concluded that the electrons are primarily located on the V1 zigzag chains. The anisotropy of the linewidth, which is determined by the intrachain symmetric anisotropic exchange interaction, favors statistic electron distribution in the metallic and blockwise charge-order in the insulating phase. The temperature dependence of the linewidth indicates the opening of a charge gap at the metal-to-insulator transition at T(MI)=132 K.

Journal Article↗
PubMed2004

Antimalarial activity of extracts of Abutilon grandiflorum G. Don - a traditional Tanzanian medicinal plant.

The Tanzanian medicinal plant Abutilon grandiflorum G. Don was studied for its in vivo and in vitro antiplasmodial effects. The ethyl acetate extract showed prominent in vivo activity against P. vinckei vinckei in mice and in vitro against P. falciparum strains HB3 and FCB. The extract was only moderately cytotoxic if tested in vitro against the colon cell line HT29. In the in vivo study, the results were significantly influenced by the treatment schedule used, i.e. early treatment with higher doses was more successful than applying the same overall amount over a longer period. Phytochemical analysis of the extract provided no conclusive evidence for the observed parasitological effects.

Animals↗
PubMed2004

Cathepsin D links TNF-induced acid sphingomyelinase to Bid-mediated caspase-9 and -3 activation.

Acidic noncaspase proteases-like cathepsins have been introduced as novel mediators of apoptosis. A clear role for these proteases and the acidic endolysosomal compartment in apoptotic signalling is not yet defined. To understand the role and significance of noncaspases in promoting and mediating cell death, it is important to determine whether an intersection of these proteases and the caspase pathway exists. We recently identified the endolysosomal aspartate protease cathepsin D (CTSD) as a target for the proapoptotic lipid ceramide. Here, we show that tumor necrosis factor (TNF)-induced CTSD activation depends on functional acid sphingomyelinase (A-SMase) expression. Ectopic expression of CTSD in CTSD-deficient fibroblasts results in an enhanced TNF-mediated apoptotic response. Intracellular colocalization of CTSD with the proapoptotic bcl-2 protein family member Bid in HeLa cells, and the ability of CTSD to cleave directly Bid in vitro as well as the lack of Bid activation in cathepsin-deficient fibroblasts indicate that Bid represents a direct downstream target of CTSD. Costaining of CTSD and Bid with Rab5 suggests that the endosomal compartments are the common 'meeting point'. Caspase-9 and -3 activation also was in part dependent on A-SMase and CTSD expression as revealed in the respective deficiency models. Our results link as novel endosomal intermediates the A-SMase and the acid aspartate protease CTSD to the mitochondrial apoptotic TNF pathway.

Animals↗
PubMed2004

Conscious sedation: Off-label use of rectal S(+)-ketamine and midazolam for wound dressing changes in paediatric heat injuries.

BACKGROUND: Wound dressing changes after heat injuries expose the patient to repeated painful and frightening procedures in short intervals. Safe, adequate, and easily administered analgesia and sedation are required. The goal of this study was to evaluate the off-label use of rectally administered S(+)-ketamine and Midazolam by paediatric surgeons during repeated outpatient dressing changes for paediatric burns and scalding. PATIENTS AND METHODS: A total of 47 dressing changes of 30 children with I - IIa degrees burns were evaluated. Vital signs, side-effects, complications, anxiolysis, and analgesia were recorded during the procedure and for the following two hours. Patients were assessed by a discharge scoring system and an age-appropriate pain scoring system at regular intervals. Before discharge, parents were interviewed on their level of satisfaction with the protocol. RESULTS: Adequate sedation and analgesia was achieved in 44 procedures (94 %). No complications and, in particular, no compromise of breathing, ventilatory, and cardiovascular functions were recorded. The discharge scoring system indicated a return to baseline function 30 minutes after the procedure in all patients. The parents were generally very satisfied with the protocol. All children old enough to be questioned were found to have an anterograde amnesia for the duration of the procedure. CONCLUSION: Conscious sedation with rectally applied S(+)-ketamine and Midazolam allows safe and painless dressing changes after heat injuries in children.

Adjuvants, Anesthesia↗
PubMed2004

Phenylpropanoid NF-kappaB inhibitors from Bupleurum fruticosum.

Two phenylpropanoids from Bupleurum fruticosum (Apiaceae/Umbelliferae) were shown to inhibit the transcriptional activity induced by PMA or TNFalpha of an NF-kappaB-controlled reporter gene. Western blot experiments indicated that the phenylpropanoids did not prevent IkappaBalpha degradation, suggesting that their molecular target is at a post-IKB degradation level. Both compounds prevented cytokine (IL-1, IL-6, TNF, IL-8) release and prostaglandin E2 synthesis.

Apiaceae↗
PubMed2003

Potential signature of a Kosterlitz-Thouless transition in BaNi2V2O8.

ESR measurements are reported for the quasi-two-dimensional honeycomb antiferromagnet BaNi2V2O8. Planar anisotropic properties are confirmed by angular dependent investigations of resonance field and linewidth. The divergence of the temperature-dependent linewidth on approaching T(N) from above is described in terms of the Kosterlitz-Thouless transition, the critical behavior close to long-range magnetic order, and the 2D Heisenberg antiferromagnet. We provide arguments that the Kosterlitz-Thouless scenario is compatible with the observed critical exponent and suggest BaNi2V2O8 is a weakly anisotropic 2D Heisenberg antiferromagnet.

Journal Article↗
PubMed2003

Perioperative dexamethasone treatment in childhood craniopharyngioma--influence on short-term and long-term weight gain.

The substitution of dexamethasone during and after surgery of childhood craniopharyngioma is necessary in order to treat and/or prevent brain edema and adrenal insufficiency. Early post-operative weight gain is a predictor for severe obesity during long-term follow-up. In a retrospective analysis of 60 patients with childhood craniopharyngioma we inquired whether dose and duration of perioperative dexamethasone therapy (n = 68) had influence on short-term post-operative weight gain and long-term development of severe obesity. The median follow-up period was 4.2 years, ranging from 1 to 9 years. 24 patients (14 f/10 m) developed severe obesity (BMI > 3 SD). 28 patients (10 f/18 m) retained normal weight (BMI < 2 SD). Eight patients presented with a BMI between 2 and 3 SD at the final visit. Differences in terms of age at surgery or follow-up period were non-detectable between the analyzed groups of craniopharyngioma patients. Duration and cumulative dexamethasone doses (mg/m2 BSA) for perioperative dexamethasone therapy were similar for severely obese patients (duration: 8.7 d; 4.5 - 17 d, cumulative dose: 74; 42 - 177 mg/m2 BSA) and normal weight patients (duration: 10.0 d; 1 - 41 d; dose: 76; 9 - 390 mg/m2 BSA). Whereas cumulative dexamethasone doses positively (p < 0.01; rho: 0.424) correlated with weight gain during the first year following surgery, long-term development of severe obesity was not influenced by dose and duration of perioperative dexamethasone treatment. Patients who developed severe obesity during follow-up had a higher (p < 0.001) BMI already at the time of diagnosis. We conclude that dose and duration of perioperative dexamethasone treatment had short-term effects on post-operative weight gain, but not on the development of long-term severe obesity. The results of our retrospective analysis are currently tested in a prospective surveillance study Kraniopharyngeom 2000 (www.kraniopharyngeom.com).

Adolescent↗
PubMed2003

Expression of KIT and epidermal growth factor receptor in chemotherapy refractory non-seminomatous germ-cell tumors.

BACKGROUND: The majority of patients with germ-cell tumors (GCTs) are curable with standard therapy. The molecular differences between curable and incurable disease are unknown. We have studied the expression of KIT and the epidermal growth factor receptor (EGFR) to determine their incidence in chemorefractory disease. PATIENTS AND METHODS: We retrospectively analyzed 23 patients with chemorefractory non-seminomatous GCTs (15 late relapse and eight transformed teratomas). None of these 23 patients were cured by their initial chemotherapy and/or surgery. Immunohistochemical analysis of KIT and EGFR was performed on the most recently available specimen from a metastatic site. PCR amplimers of KIT exon 17 were screened for mutations by a combination of denaturing high-performance liquid chromatography and direct sequencing. RESULTS: KIT was expressed (>/=10% of the tumor displaying membranous or cytoplasmic staining) in 11 of 23 GCT patients [48%; 95% confidence interval (CI) 26% to 68%]. There were no activating KIT mutations in the phosphoryltransferase domain (exon 17) in 21 patients analyzed. EGFR was expressed (1+ to 3+) in 15 of 23 GCT patients (65%; 95% CI 41% to 82%). CONCLUSIONS: KIT and EGFR are expressed in a significant proportion of refractory GCTs. The significance of these findings will be determined by ongoing clinical trials.

Adolescent↗
PubMed2002

In vitro antioxidant activity of non-cultivated vegetables of ethnic Albanians in southern Italy.

A total of 27 extracts from non-cultivated and weedy vegetables traditionally consumed by ethnic Albanians (Arbëreshë) in the Vulture area (southern Italy) were tested for their free radical scavenging activity (FRSA) in the DPPH (1,1-diphenyl-2-picrylhydrazil radical) screening assay, for their in vitro non-enzymatic inhibition of bovine brain lipid peroxidation and for their inhibition of xanthine oxidase (XO). In both antioxidant assays strong activity was shown for Leopoldia comosa (bulbs, syn.: Muscari comosum) and Centaurea calcitrapa (young whorls). In the lipid peroxidation assay, extracts from leaves of Origanum heracleoticum, Urtica dioica and Tordylium apulum showed a remarkable inhibitory activity (> 50%), too. In the case of Leopoldia comosa and Origanum heracleoticum this activity was comparable to quercetin (at a concentration of 50 microM) and Rhodiola rosea extract. Extracts from non-cultivated Cichorium intybus, Chondrilla juncea and Stellaria media showed strong in vitro inhibition of xanthine oxidase, with an activity higher than that of a reference extract from Ledum groenlandicum. These findings suggest that weedy vegetables may be useful antioxidants of interest in the prevention of ageing related diseases, CNS disorders and as potential sources of phytomedicines against hyperuricaemia and gout.

Albania↗
PubMed2002

[Perioperative pain therapy. Deficiencies in children and adolescents].

Present studies reveal that postoperative pain management for children is still insufficient in Germany. This situation is not only caused by a lack of knowledge, but, mainly, by a deficiency of standardized protocols in the hospitals and the lack of administrative responsibility. This article describes a specific concept for postoperative pain management in children. It basically focuses on three main topics: prevention of pain, the algorithm for analgesic treatment and the evaluation of the efficiency of the treatment. The surgeon plays a central role in pain prevention. By intraoperative blocking of the peripheral nerves, he can achieve effective analgesia. Postoperatively, he prescribes a basic medication according to the procedure used and the surgical trauma. Its effectiveness must be measured routinely thereafter and, depending on the score, an individual pain medication should be added. Pain measurement in children requires the application of specific scales for each age group. The evaluation of this concept has revealed therapeutic success, broad acceptance and efficiency in ward use. However a long-term benefit can only be achieved when postoperative pain management is one of the essential duties of the surgeon and it is constantly monitored within a department.

Adolescent↗
PubMed2002

cAMP and cGMP do not mediate the vasorelaxation induced by iodinated radiographic contrast media in isolated swine renal arteries.

PURPOSE: Vasodilatation is a frequent side effect of radiographic contrast media, partially due to a direct effect on vascular smooth muscles. Our purpose was therefore to examine any possible implication of the cyclic adenosine monophospate (cAMP) and cyclic guanosine monophosphate (cGMP) pathways in contrast media induced vasorelaxation. MATERIAL AND METHODS: Isolated segments of swine renal arteries were precontracted with 10 microM phenylephrine and relaxed with iomeprol before and after blockade of the cAMP and cGMP pathways. RESULTS: 80 mM and 160 mM of iomeprol significantly relaxed about 52% and 68% of the precontracted arterial rings, respectively. 10 microM of IBMX, a phosphodiesterase inhibitor, did not increase the relaxant effect of 80 mM iomeprol but increased the relaxations induced by 400 nM forskolin by about 1.9 times (which stimulates the production of cAMP), and by 1 microM sodium nitroprusside (which stimulates the production of cGMP). 1 microM of H89 (an inhibitor of the cAMP-dependent protein kinase), was able to reduce the relaxation induced by 4 microM forskolin by about 2.5 times but had no significant effect on the relaxation induced by 160 mM iomeprol. 10 microM of ODQ (an inhibitor of the soluble guanylate cyclase), could reduce the relaxation induced by 10 microM of SNP but not the one induced by 160 mM iomeprol. Moreover, the absence of endothelial cells did not alter the relaxation induced by iomeprol. CONCLUSION: The activation of the cAMP and cGMP pathways are not involved in the in vitro relaxation induced by iomeprol in swine renal arteries.

Animals↗
PubMed2002

Cloning and expression analysis of SALL4, the murine homologue of the gene mutated in Okihiro syndrome.

SALL4 is one out of four human homologues of the DROSOPHILA region-specific homeotic gene SPALT(SAL). Heterozygous mutations of SALL4 on chromosome 20q13.13--> q13.2 cause the autosomal dominant Okihiro syndrome which is characterized by radial limb defects, Duane anomaly and hearing loss. We have partially cloned the murine homologue of this gene, named SALL4, and completed the coding sequence by comparison to available EST and genomic sequences in the GenBank database. This comparison also revealed the chromosomal location of SALL4 on mouse chromosome 2H3 and suggested that a predicted testis expressed gene TEX20 at the very same locus is most likely not a gene on its own but part of the SALL4 3' UTR. We analyzed the expression of SALL4 during early embryogenesis by whole mount in situ hybridization and in the adult mouse by Northern blotting. In adult tissues, SALL4 expression is only found in testis and ovary. During embryonic development, SALL4 expression is widespread in early embryos and becomes gradually confined to the head region and the primitive streak. Prominent expression in the developing midbrain, branchial arches and the limbs suggests an important function of SALL4 during development of these structures as expected from the observation in Okihiro syndrome patients.

Age Factors↗
PubMed2002

Spasmolytic effects of baccharis conferta and some of its constituents.

The Nahua of the Mexican state of Veracruz use Baccharis conferta in the treatment of a variety of gastrointestinal illnesses, especially diarrhoea associated with gastrointestinal cramps. The aerial parts of B. conferta were investigated phytochemically and pharmacologically using the guinea pig ileum assay as a model (histamine, KCI and electric stimulation). The crude ethanolic extract showed a dose-dependent antispasmodic effect that was particularly strong in flavonoid-rich fractions (e.g. IC50 value for fraction E.3.1 from the ethyl acetate fraction, in histamine-induced contraction, 10 microg mL(-1)). Several flavonoids (apigenin-4',7-dimethylether, naringenin-4',7-dimethylether, pectolinarigenin and cirsimaritin) were isolated, while others were identified in complex fractions by GC-MS. The flavonoids play an important role in the antispasmodic activity of this indigenous drug. Additionally, oleanolic acid and its methyl ester as well as erythrodiol were isolated. Oleanolic acid methyl ester shows weak antibacterial activity against M. luteusand E. coli (20 microg/spot in a TLC assay). The phytochemical as well as the pharmacological data provide some in-vitro evidence forthe use of B. conferta in thetreatment of gastrointestinal cramps.

Animals↗
PubMed2001

CD95 and TRAIL receptor-mediated activation of protein kinase C and NF-kappaB contributes to apoptosis resistance in ductal pancreatic adenocarcinoma cells.

The molecular alterations in tumour cells leading to resistance towards apoptosis induced by CD95 and TRAIL-receptors are not fully understood. We report here that the stimulation of the CD95- and TRAIL-resistant human pancreatic adenocarcinoma cell line PancTuI with an agonistic anti-CD95 antibody or TRAIL resulted in activation of protein kinase C and NF-kappaB. Inhibition of protein kinase C by Gö6983 sensitized these cells to apoptotic challenges and strongly diminished activation of NF-kappaB by anti-CD95 and TRAIL. Similarly, inhibition of NF-kappaB by MG132 or by transient transfection with a dominant negative mutant of IkappaBalpha restored the responsiveness of PancTuI cells to both death ligands. In the CD95 and TRAIL-sensitive cell line Colo357 the induction of protein kinase C and NF-kappaB following activation of CD95 and TRAIL-R was very moderate compared with PancTuI cells. However, pre-incubation of these cells with PMA strongly reduced their apoptotic response to anti-CD95 and TRAIL. Taken together, we show that activation of protein kinase C operates directly in a death receptor-dependent manner in PancTuI cells and protect pancreatic tumour cells from anti-CD95 and TRAIL-mediated apoptosis by preventing the loss DeltaPsim and Cytochrome c release as well as by induction of NF-kappaB.

Adenocarcinoma↗
PubMed2001

Pheophorbide A from Solanum diflorum interferes with NF-kappa B activation.

Continuing our search for biogenic NF-kappa B inhibitors we investigated Solanum diflorum, used by the Istmo Sierra Zapotec Indians of Mexico in the treatment of inflammatory skin conditions. It became obvious very early that the active substance seems to be a degradation product of chlorophyll. Pheophorbide A was identified as one of the key compounds responsible for the NF-kappa B inhibitory activity. The compound interferes with NF-kappa B activation, was cytotoxic if exposed to light, but devoid of any cytotoxic activity in the dark.

Anti-Inflammatory Agents, Non-Steroidal↗