Cephalic phase salivary response differences characterize level of food neophobia.
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Adult↗
Biomedical subjects
B Meyer
Publications and source records attributed to B Meyer.
Comparison of two test methods for the determination of sufficient antimicrobial activity of three commonly used alcohol-based hand rubs for hygienic hand disinfection.
In Europe, the antimicrobial efficacy of alcohol-based hand rubs is determined with a quantitative suspension test (prEN 12054) and a test under practical conditions (EN 1500). Another test method has recently been published by the German Society for Hygiene and Microbiology (DGHM) with four differences to the European system in the in vitro tests: additional qualitative suspension tests with product dilutions to the ineffective range; a selection of the most resistant Gram-negative test strains in the qualitative suspension test, which should be used adjacent to Pseudomonas aeruginosa in the quantitative suspension test; a high organic load in the quantitative suspension tests (0.3% albumin and 0.3% sheep erythrocytes); and an aqueous control in the quantitative suspension test. According to DGHM, the in vitro tests should be followed by EN 1500. We have determined the antimicrobial efficacy of three commonly used alcohol-based hand rubs according to both methods. prEN 12054 was carried out without organic load. The qualitative suspension tests (DGHM) were carried out with P. aeruginosa, Escherichia coli, Proteus mirabilis, Staphylococcus aureus, Enterococcus hirae and Candida albicans. The quantitative suspension test (DGHM) was carried out with product dilutions of 75%, 50% and 25%, and a high organic load using the following test organisms: P. aeruginosa, P. mirabilis (one product only), S. aureus, E. hirae and C. albicans. All these suspension tests were carried out in quadruplicate with each product and exposure time. EN 1500 was carried out with 3 mL of each product and an application time of 30 s. All three products achieved the required bactericidal activity of prEN 12054 and the new DGHM method within 30 s, and were equally effective with the reference hand disinfection of EN 1500 within 30 s. In our study, the DGHM test method did not provide additional information for hand rubs which exhibit their bactericidal efficacy with 3 mL within 30 s (EN 1500).
Alcohols↗
The canine HMGA1 gene maps to CFA 23.
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Animals↗
[Preliminary experience with balloon kyphoplasty for the treatment of painful osteoporotic compression fractures].
PURPOSE: To describe the technique and to evaluate the safety and efficacy of percutaneous kyphoplasty as a new treatment in patients with painful osteoporotic vertebral body compression fractures of the lumbar and thoracic spine. MATERIALS AND METHODS: In this prospective study balloon kyphoplasty was performed in 34 consecutive patients (25 females, 9 males; mean age 75 years) with 56 painful osteoporotic vertebral fractures (from T6-L5), of which 22 showed a posterior wall involvement and retropulsion on preoperative CT. The median duration of symptoms was 9.7 weeks. Symptomatic levels were identified by correlating the clinical presentation with MRI, conventional radiographs and CT including bone-densitometry. Pre- and postoperative examinations (radiographs, CT) as well as Karnofsky and visual analogy pain scores (Visual Analog Scale = VAS) were documented and compared to evaluate the success of the procedure. RESULTS: The median Karnofsky score improved from 40 % (pre-) to 70 % (post-treatment). Simultaneously, median pain scores (VAS) decreased from 64 (pre-) to 21 (post-treatment) (p < 0.001). Perioperative morbidity included one transient L2 nerve root bruise. The procedure led to a partial restoration of the height of the vertebral body by reducing the median sagittal index from 11.5(3) to 5(3). In none of our patients, the procedure led to worsening of the fracture-induced narrowing of the spinal canal. Clinically asymptomatic cement leakage occurred in 10 cases, with leakage 4 times into the paraspinal space, 3 times into the spinal canal and 3 times into the disc space. CONCLUSION: Balloon kyphoplasty is a safe and effective procedure. It is applicable even in fractures with posterior wall involvement since it is a low-pressure technique in contrast to vertebroplasty and restores vertebral body height partially. It results in immediate clinical improvement of mobility and pain relief. While short-term results are excellent, follow-up data have to be awaited for the final judgment of this method.
Aged↗
L-Asparaginase-associated hyperlipidemia with hyperviscosity syndrome in a patient with T-cell lymphoblastic lymphoma.
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Adult↗
Molecular characterization of the canine HMGB1.
Due to the close similarities of numerous canine diseases to their human counterparts, the dog could join the mouse as the species of choice to unravel the genetic background of complex diseases as e.g. cancer and metabolic diseases. Accordingly, the role of the dog as a model for therapeutic approaches is strongly increasing. However, prerequisite for such studies is the characterization of the corresponding canine genes. Recently, the human high mobility group protein B1 (HMGB1) has attracted considerable interest of oncologists because of what is called its "double life". Besides its function as an architectural transcription factor HMGB1 can also be secreted by certain cells and then acts as a ligand for the receptor for advanced glycation end products (RAGE). The binding of HMGB1 to RAGE can activate key cell signaling pathways, such as p38(MAPK), JNK, and p42/p44(MAPK) emphasizing the important role of HMGB1 in inflammation and tumor metastasis. These results make HMGB1 a very interesting target for therapeutic studies done in model organisms like the dog. In this study we characterized the molecular structure of the canine HMGB1 gene on genomic and cDNA levels, its predicted protein, the gene locus and a basic expression pattern.
Amino Acid Sequence↗
The human kidney is a progesterone-metabolizing and androgen-producing organ.
Progesterone (P) is a potent antagonist of the human mineralocorticoid receptor (MR) in vitro. We have previously demonstrated effective downstream metabolism of P in the kidney. This mechanism potentially protects the MR from P action. Here, we have investigated the expression and functional activity of steroidogenic enzymes in human kidney. RT-PCR analysis demonstrated the expression of 5 alpha-reductase type 1, 5 beta-reductase, aldo-keto-reductase (AKR) 1C1, AKR1C2, AKR1C3, 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) type 2, and 17 alpha-hydroxylase/17,20-lyase (P450c17). The presence of 3 beta-HSD type 2 and P450c17 indicated that conversion of pregnenolone to dehydroepiandrosterone (DHEA) and to androstenedione may take place effectively in kidney. To investigate this further, we incubated kidney subcellular fractions with radiolabeled pregnenolone. This resulted in efficient formation of DHEA from pregnenolone, indicating both 17 alpha-hydroxylase and 17,20-lyase activities exerted by P450c17. Radiolabeled DHEA was converted via androstenedione, androstenediol, and testosterone, indicating both 3 beta-HSD type 2 activity and 17 beta-HSD activity. In addition, the conversion of testosterone to 5 alpha-dihydrotestosterone was detectable, indicating 5 alpha-reductase activity. In conclusion, we verified the expression and functional activity of several enzymes involved in downstream metabolism of P and androgen synthesis in human kidney. These findings may be critical to the understanding of water balance during the menstrual cycle and pregnancy and of sex differences in hypertension.
Androgens↗
Renal inactivation, mineralocorticoid generation, and 11beta-hydroxysteroid dehydrogenase inhibition ameliorate the antimineralocorticoid effect of progesterone in vivo.
Progesterone (P) is a strong mineralocorticoid receptor (MR) antagonist in vitro. The high P concentrations seen in normal pregnancy only moderately increase renin and aldosterone concentrations. In previous in vitro studies we hypothesized that this may be explained by intrarenal conversion of P to less potent metabolites. To investigate the in vivo anti-MR potency of P, we performed an infusion study in patients with adrenal insufficiency (n = 8). They omitted 9alpha-fluorocortisol for 4 d and hydrocortisone for 0.5 d before a continuous iv infusion of aldosterone for 8.5 h, with an additional iv P infusion commenced at 4 h. During aldosterone infusions the initially elevated urinary sodium to potassium ratio decreased significantly. Despite the 1000-fold excess of P over aldosterone, the urinary sodium to potassium ratio and urinary sodium excretion increased only slightly after 3 h of P infusion. We detected inhibition of renal 11beta-hydroxysteroid dehydrogenase type 2 by P, thus giving cortisol/prednisolone access to the MR. Urinary and plasma concentrations of 17alpha-hydroxyprogesterone, a major metabolite of renal P metabolism, and those of serum androstenedione and deoxycorticosterone, a mineralocorticoid itself, increased significantly during P infusion. This supports the hypothesis of an effective protection of the MR from P by efficient extraadrenal downstream conversion of P.
11-beta-Hydroxysteroid Dehydrogenases↗
[Address by the President of the Society of Laryngology in the hospitals of Paris].
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Catchment Area, Health↗
Massive postoperative intramuscular bleeding in acquired von Willebrand's disease.
We describe a case of acquired von Willebrand's disease (vWD) associated with monoclonal gammopathy with undetermined significance (MGUS) in a 54-year-old man who was admitted with hemarthrosis and extensive thigh muscle hematoma following arthroscopic surgery and postoperative prophylaxis with low molecular weight heparin. Coagulation tests were compatible with acquired vWD: prolonged activated partial thromboplastin time (aPTT) (56.1 s), decreased levels of factor VIII coagulant activity (23%), low concentrations of von Willebrand's factor (vWF) antigen (13%), and undetectable ristocetin cofactor activity (<10%). Infusion of a vWF-containing factor VIII concentrate failed to normalize the plasma levels of vWF-related parameters. Only additional intravenous administration of immunoglobulins led to a transient normalization of ristocetin cofactor activity, vWF antigen, and factor VIII coagulant activity. While the spontaneous bleeding tendency in this case was mild, surgery and administration of prophylactic doses of low molecular weight heparin led to life-threatening bleeding.
Arthroscopy↗
A fluorometric method for the differentiation of algal populations in vivo and in situ.
Fingerprints of excitation spectra of chlorophyll (Chl) fluorescence can be used to differentiate 'spectral groups' of microalgae in vivo and in situ in, for example, vertical profiles within a few seconds. The investigated spectral groups of algae (green group, Chlorophyta; blue, Cyanobacteria; brown, Heterokontophyta, Haptophyta, Dinophyta; mixed, Cryptophyta) are each characterised by a specific composition of photosynthetic antenna pigments and, consequently, by a specific excitation spectrum of the Chl fluorescence. Particularly relevant are Chl a, Chl c, phycocyanobilin, phycoerythrobilin, fucoxanthin and peridinin. A laboratory-based instrument and a submersible instrument were constructed containing light-emitting diodes to excite Chl fluorescence in five distinct wavelength ranges. Norm spectra were determined for the four spectral algal groups (several species per group). Using these norm spectra and the actual five-point excitation spectrum of a water sample, a separate estimate of the respective Chl concentration is rapidly obtained for each algal group. The results of dilution experiments are presented. In vivo and in situ measurements are compared with results obtained by HPLC analysis. Depth profiles of the distribution of spectral algal groups taken over a time period of few seconds are shown. The method for algae differentiation described here opens up new research areas, monitoring and supervision tasks related to photosynthetic primary production in aquatic environments.
Journal Article↗
HLA class II sequence-based typing in normal Saudi individuals.
We have adopted a system that combines low resolution PCR-SSP followed by sequence-based typing (SBT) to analyze HLA-DRB1, -DPB1 and -DQB1 alleles in the Saudi population. The SBT method was used to identify HLA class II alleles in Saudis for the first time. Nineteen HLA-DRB1 alleles in currently recognized subtypes of the DRB locus were detected. DR1 and DR9 were not encountered. SBT did not detect diversity within the DR7 and DR10 alleles. Sixteen HLA-DQB1 and 10 HLA-DPB1 alleles were identified. This study represents the first molecular report on the HLA class II allele frequency in the population of Saudi Arabia.
Arabs↗
Results for microsurgical removal of tentorial meningiomas.
OBJECTIVE: Growth patterns of tentorial meningiomas are related to the deep cerebral venous system and to cranial nerves IV-XI. Localization and surgical aggressiveness are decisive for the outcome to be expected. PATIENTS AND METHODS: n = 25 patients (22 f, 3 m), aged from 26-77 (mean: 56.4) years underwent microsurgical removal of their tentorial meningioma. Tumor size was as follows: n = 11 < 3 cm, n = 6 3-5 cm, n = 8 > 5 cm. The median of the preoperative Karnofsky scores was 90. The operative approaches chosen were suboccipital in n = 14, subtemporal in n = 6, occasionally a combined supra- and infratentorial approach was chosen. Data regarding surgery, histology and postoperative course were available through the patient's charts and through outpatient clinic. RESULTS: n = 20 (80%) of the tumors were rated WHO grade I, n = 5 (20%) WHO grade II. Tumor removal according to Simpson was degrees I in n = 9 (36%), degrees II in n = 14 (56%), degrees III in n = 2 (8%). Mortality was 0%. In n = 6 patients (24%) neurological worsening, mainly due to transient cranial nerve deficits was noted. Surgical complications (CSF fistula, wound healing problems) occurred in n = 5 patients (20%). The median of the postoperative Karnofsky scores on last follow up was 90 after a median of 41.9 months. Two patients (8%), one of whom underwent reoperation developed tumor recurrency during follow up. CONCLUSIONS: Neurological deficits following microsurgical removal of tentorial meningiomas are transient in the majority of patients. The apparently high rate of incomplete tumor resection (app. 60% Simpson grades II and III) is due to the close topographical relationship of these tumors with important neurovascular structures. Thus, the operative strategy should not be excessively aggressive, but rather take into account the option to observe residual tumor or to apply additional stereotactic convergent beam radiation in selected cases.
Adult↗
Monitoring of donor/recipient T-cell engraftment kinetics in myeloablative allogeneic stem cell transplantation using short tandem repeat amplification from cell lysates.
Molecular monitoring of donor/recipient T-cell kinetics early post-transplant can provide clues to the immunological events that govern host-versus-graft reaction (HVGR) and graft versus-host-disease (GVHD). We have previously used fluorescence in situ hybridization (FISH) with X and Y probes to monitor recipient T (R-T) cell clearance early after myeloablative allogeneic stem cell transplantation (ASCT). We demonstrated that impaired clearance of residual host-T-cells in the early days post-transplant was associated with graft rejection, while enhanced clearance could be an indicator of increased donor anti-host alloreactivity and predictive of acute GVHD. Although FISH is the most accurate quantitative molecular tool for the determination of the exact donor/recipient-T-cell numbers at any time points post-transplant, it has the disadvantage of being limited to sex mismatched donor/recipient pairs. Our goal was to develop a molecular approach that, irrespective of gender, would be comparable to FISH in accurately determining host residual T-cell clearance after myeloablative conditioning for ASCT. We have genotyped DNA from cell lysates using polymerase chain reaction (PCR) amplification of short tandem repeats (STR) with fluorescently labeled oligonucleotide primers, and used the Genescan 672 software for accurate quantitative analysis of the amplified alleles. Here, we show that this approach allowed us to achieve in T-cells accurate quantitative analyses of amplified donor/recipient alleles in sex matched patients on days +5, +8 and +12 post-transplant, despite severe leukopenia.
Adolescent↗
Agonistic and antagonistic properties of progesterone metabolites at the human mineralocorticoid receptor.
OBJECTIVE: Progesterone binds to the human mineralocorticoid receptor (hMR) with nearly the same affinity as do aldosterone and cortisol, but confers only low agonistic activity. It is still unclear how aldosterone can act as a mineralocorticoid in situations with high progesterone concentrations, e.g. pregnancy. One mechanism could be conversion of progesterone to inactive compounds in hMR target tissues. DESIGN: We analyzed the agonist and antagonist activities of 16 progesterone metabolites by their binding characteristics for hMR as well as functional studies assessing transactivation. METHODS: We studied binding affinity using hMR expressed in a T7-coupled rabbit reticulocyte lysate system. We used co-transfection of an hMR expression vector together with a luciferase reporter gene in CV-1 cells to investigate agonistic and antagonistic properties. RESULTS: Progesterone and 11beta-OH-progesterone (11beta-OH-P) showed a slightly higher binding affinity than cortisol, deoxycorticosterone and aldosterone. 20alpha-dihydro(DH)-P, 5alpha-DH-P and 17alpha-OH-P had a 3- to 10-fold lower binding potency. All other progesterone metabolites showed a weak affinity for hMR. 20alpha-DH-P exhibited the strongest agonistic potency among the metabolites tested, reaching 11.5% of aldosterone transactivation. The agonistic activity of 11beta-OH-P, 11alpha-OH-P and 17alpha-OH-P was 9, 5.1 and 4.1% respectively. At a concentration of 100 nmol/l, progesterone, 17alpha-OH-P and 20alpha-DH-P inhibit nearly 75, 40 and 35% of the transactivation by aldosterone respectively. All other progesterone metabolites tested demonstrate weaker affinity, and agonistic and antagonistic potency. CONCLUSIONS: The binding affinity for hMR and the agonistic and antagonistic activity diminish with increasing reduction of the progesterone molecule at C20, C17 and at ring A. We assume that progesterone metabolism to these compounds is a possible protective mechanism for hMR. 17alpha-OH-P is a strong hMR antagonist and could exacerbate mineralocorticoid deficiency in patients with congenital adrenal hyperplasia.
Aldosterone↗
Oblique stepwise rise and growth of the Tibet plateau.
Two end member models of how the high elevations in Tibet formed are (i) continuous thickening and widespread viscous flow of the crust and mantle of the entire plateau and (ii) time-dependent, localized shear between coherent lithospheric blocks. Recent studies of Cenozoic deformation, magmatism, and seismic structure lend support to the latter. Since India collided with Asia approximately 55 million years ago, the rise of the high Tibetan plateau likely occurred in three main steps, by successive growth and uplift of 300- to 500-kilometer-wide crustal thrust-wedges. The crust thickened, while the mantle, decoupled beneath gently dipping shear zones, did not. Sediment infilling, bathtub-like, of dammed intermontane basins formed flat high plains at each step. The existence of magmatic belts younging northward implies that slabs of Asian mantle subducted one after another under ranges north of the Himalayas. Subduction was oblique and accompanied by extrusion along the left lateral strike-slip faults that slice Tibet's east side. These mechanisms, akin to plate tectonics hidden by thickening crust, with slip-partitioning, account for the dominant growth of the Tibet Plateau toward the east and northeast.
Journal Article↗
Determination of the binding specificity of an integral membrane protein by saturation transfer difference NMR: RGD peptide ligands binding to integrin alphaIIbbeta3.
Saturation transfer difference (STD) NMR is a fast and versatile method to screen compound mixtures in the presence of a receptor for binding affinity and to characterize the ligand's binding epitope. Here we demonstrate that ligand interactions with integral membrane proteins can be investigated by STD NMR if the receptor is embedded into the lipid bilayer of a liposome. The integrin alphaIIbbeta3, also termed GPIIb-IIIa, is a platelet surface glycoprotein that plays a pivotal role in platelet aggregation and that interacts with proteins and peptides presenting the peptide recognition motif RGD. Purified human integrin alphaIIbbeta3 was incorporated into liposomes, and the binding of RGD peptides was analyzed by STD NMR techniques. Cyclo(RGDfV) gave STD NMR effects in the presence of liposomes containing the integrin. The magnitude of the STD effect as a function of the ligand's concentration gave a value for the dissociation constant of 30-60 microM. Adding the weakly binding RGD to the solution of cyclo(RGDfV) resulted in STD effects of the stronger ligand cyclo(RGDfV) only. This demonstrates in agreement with literature that the peptide RGD is a much weaker ligand to the integrin than the peptide cyclo(RGDfV) that largely replaces the RGD peptides from the binding site. The binding epitope of the ligand cyclo(RGDfV) was characterized by STD NMR to contain sections of the D-Phe, the Val methyl groups, Arg alpha, beta, and gamma protons, one Hbeta of Asp, and one Halpha of Gly.
Epitopes↗
Group epitope mapping by saturation transfer difference NMR to identify segments of a ligand in direct contact with a protein receptor.
A protocol based on saturation transfer difference (STD) NMR spectra was developed to characterize the binding interactions at an atom level, termed group epitope mapping (GEM). As an example we chose the well-studied system of galactose binding to the 120-kDa lectin Ricinus communis agglutinin I (RCA(120)). As ligands we used methyl beta-D-galactoside and a biantennary decasaccharide. Analysis of the saturation transfer effects of methyl beta-D-galactoside showed that the H2, H3, and H4 protons are saturated to the highest degree, giving evidence of their close proximity to protons of the RCA(120) lectin. The direct interaction of the lectin with this region of the galactose is in excellent agreement with results obtained from the analysis of the binding specificities of many chemically modified galactose derivatives (Bhattacharyya, L.; Brewer, C. F. Eur. J. Biochem. 1988, 176, 207-212). This new NMR technique can identify the binding epitope of even complex ligands very quickly, which is a great improvement over time-consuming chemical modifications. Efficient GEM benefits from a relatively high off rate of the ligand and a large excess of the ligand over the receptor. Even for a ligand like the biantennary decasaccharide with micromolar binding affinity, the binding epitopes could easily be mapped to the terminal beta-D-Gal-(1-4)-beta-D-GlcNAc (beta-D-GlcNAc = N-acetyl-D-glucosamine) residues located at the nonreducing end of the two carbohydrate chains. The binding contribution of the terminal galactose residue is stronger than those of the penultimate GlcNAc residues. We could show that the GlcNAc residues bind "edge-on" with the region from H2 to H4, making contact with the protein. Analysis of STD NMR experiments performed under competitive conditions proved that the two saccharides studied bind at the same receptor site, thereby ruling out unspecific binding.
Acetylglucosamine↗