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Biomedical subjects

A Ziegler

Publications and source records attributed to A Ziegler.

At least 127 records · Page 7Linked to original sources

NMR imaging of thermally polarized helium-3 gas.

It is shown that thermally polarized 3He gas can be used to measure important physical parameters and to design, test, and tune imaging sequences. The bulk values of T1, T2, and the diffusion coefficient were measured in a glass cell containing a mixture of helium-3 (0.8 bar) and oxygen (0.2 bar). They were found to be T1 = 7 s, T2 = 2.4 s, and D = 1.6 cm2 s(-1). The relaxation times T2* and T1 and the apparent diffusion coefficient of thermally polarized helium-3 gas were measured in the rat lung, and these parameters were used to design a helium-3 optimized multi-spin-echo sequence which was shown to increase the signal-to-noise ratio sufficiently to obtain the first NMR-images of thermally polarized helium-3 in the rat lung.

Animals↗

Membrane particle distribution in the sternal epithelia of the terrestrial isopod Porcellio scaber latr. (Crustacea, oniscidea) during CaCO(3) deposit formation and resorption, a freeze-etch analysis.

The anterior sternal epithelium of terrestrial isopods transports cuticular Ca(2+) to and from large sternal CaCO(3) deposits. We analyzed the anterior and posterior sternal epithelium by the means of the freeze-etch technique and measured the size distribution and density of intramembrane particles (IMPs) during three different molting stages. At least three IMP size classes around 4.5, 7.7, and 9.4 nm can be distinguished on the P-face of the apical and basolateral plasma membrane. An additional size class of around 12.8 nm is restricted to the apical compartment. In the anterior sternal epithelium, the density of these large particles changes by a factor of 1.9 during the molt cycle, suggesting a role in CaCO(3) formation and/or resorption. The density of the smaller IMPs rises transiently by a factor of 1.3 in the posterior sternal epithelium only. The IMP density of the basolateral plasma membrane increases significantly by a factor of 1.4 and 1.3 in the anterior and posterior sternal epithelia, respectively. The results indicate that increases in the IMP density contribute to the differentiation to an increased transport activity during the cyclic enlargements of the plasma membrane surface area in the anterior sternal epithelium.

Animals↗

Sampling strategies for model free linkage analyses of quantitative traits: implications for sib pair studies of reading and spelling disabilities to minimize the total study cost.

One approach to establish linkage is based on allele sharing methods for sib pairs. In recent years the use of selected sib pairs to increase power for mapping quantitative traits in humans has been discussed intensively. In this paper the different basic principles for sib pair sampling proposed in the literature are made evident. Implications for ascertainment schemes of sib pairs to minimize the total study cost in linkage analyses on reading and spelling disabilities are discussed.

Child↗

[Body weight regulation in anorexia nervosa with special attention to leptin secretion].

Underweight is a key symptom in anorexia nervosa. In this review we summarize recent findings pertaining to weight regulation in this eating disorder. The observation that a body mass index below 13 kg/m2 upon admission for inpatient treatment is associated with a high mortality rate and chronic persistence of underweight is of obvious clinical relevance. A lowered leptin secretion, which results from the weight loss, is presumably of major importance for the development of amenorrhea. We discuss findings pertaining to a reduced body weight in other psychiatric disorders during adolescence in the light of Kretschmer's findings related to body frame and psychopathology.

Animals↗

Nasal decongestion with imidazoline derivatives: acoustic rhinometry measurements.

OBJECTIVE: The objective of this single-blind study was to establish whether there are any differences between conventional imidazoline-containing nasal drops with regard to duration of action and decongestion potential. METHODS: Six different substances were each administered to 108 healthy volunteers (nine groups of 12 adults), respectively, in the concentration recommended for adults (and two also in that recommended for infants) over a period of 8 h in comparison with 0.9% NaCl. The volumetric measurement of the nasal lumen was conducted by means of acoustic rhinometry (Rhinoklack). RESULTS: The decongestive effect of all imidazoline preparations set in relatively uniformly, without any appreciable differences. After 20 min all the products exhibited approximately 60% of their maximum decongestive effect, which was achieved after approximately 40 min, having produced an increase in volume of approximately 20%. In contrast, in terms of duration of action, considerable differences between the individual products were to be discerned: indanazoline 0.118%, naphazoline 0.02% and tetryzoline 0.1% had no effect whatsoever after 4 h. Oxymetazoline 0.05% and 0.01%, xylometazoline 0.025% and 0.1%, and tramazoline 0.1264% still had an appreciable effect after 4 h, while after 8 h only oxymetazoline 0.05% and 0.01% still had a relevant decongestive effect. A rebound effect associated with reactive hyperaemia was observed after 8 h in all short-acting products (indanazoline, naphazoline, tetryzoline and tramazoline), which in the case of indanazoline was even associated with a reduction in the nasal lumen. Interestingly, there were no differences between the xylometazoline and oxymetazoline concentrations recommended for adults and those for infants in terms of efficacy. The low-dose concentrations of the preparations for infants appear to be sufficient to produce a satisfactory therapeutic effect.

Acoustics↗

Genomic organization of the HSET locus and the possible association of HLA-linked genes with immotile cilia syndrome (ICS).

The kinesin-related protein (HSET) gene belongs to the kinesin superfamily, the members of which are involved in cellular transport processes. The HSET gene product was previously characterized by partial cDNA sequencing. The gene is located on the short arm of human Chromosome 6 (6p21.3), at the centromeric end of the major histocompatibility complex. Here, we report the genomic structure of the complete HSET gene together with its flanking loci. Sequence analysis of the 40 kilobase (kb) cosmid clone containing the HSET gene also revealed the presence of several new genes not related to the kinesin superfamily. These include a 60S ribosomal protein L35A-like pseudogene (rPL35A-like) on the telomeric side and a polycomb-like gene (PHF1), a copper tolerance-like gene (CUTA1) and the 5' part of the synaptic ras-GTPase-activating protein (SynGAP) gene centromeric of HSET. In addition, a complete 60S ribosomal protein L12-like (rPL12L) gene in intron 3 of the HSET gene was identified which appears to have an open reading frame. The possible involvement of the HSET gene and a beta-tubulin gene (TUBB) in the pathogenesis of immotile cilia syndrome (ICS) was studied by screening two unrelated ICS families with microtubular defects and suspected HLA linkage for mutations within the HSET gene and the TUBB gene. Four single base substitutions were detected in the HSET gene, and none in the TUBB gene. On the basis of these data, a role of the HSET and TUBB products in the pathogenesis of ICS in the two families is unlikely.

Amino Acid Sequence↗

Organization of the leukocyte receptor cluster (LRC) on human chromosome 19q13.4.

A large number of cDNAs coding for killer cell inhibitory receptors (KIR) and immunoglobulin-like transcripts (ILT) have already been described, and some of the respective genes are known to map in 19q13.4. To understand the genetic relationships of these transcripts, some of which may be alleles from polymorphic loci, it is necessary to determine the genomic organization of the region. To do so, we performed long-range restriction enzyme mapping of the 19q13.4 region along with YAC and PAC contig construction. Eighteen genes could be assigned to a chromosomal segment of about 600 kb. Twelve KIR loci are contained within approximately 200 kb, bordered by the locus for the Fc receptor for IgA (FCAR) at the telomeric side and by a 150-kb cluster containing ILT loci at the centromeric side. A further region with a maximal size of 135 kb containing at least one ILT gene was identified further centromeric, separated by approximately 50 kb from the ILT region near the KIR cluster. The entire KIR/ILT region revealed a considerable degree of genetic polymorphism as shown, for example, by different restriction maps of two sets of PACs spanning the same region. We suggest the designation "Leukocyte Receptor Cluster" (LRC) for this chromosomal segment.

Antigens, CD↗

Sympathomimetic effects of Parquetina nigrescens (Periplocaceae) extract in isolated portal vein smooth muscle.

The purpose of this study was to examine the mechanisms underlying the pharmacological effects of the extract of Parquetina nigrescens (Expar) on vascular smooth muscle contractility. To evaluate the Expar effect, the contractile activity of portal veins isolated from Wistar Kyoto rats was isometrically recorded. Isolated portal vein preparations developed rhythmic and spontaneous contractile activity. Expar increased the contractile response of the portal vein preparations in a dose-dependent manner. The maximal effect of the dose-response curve for Expar was prevented by the alpha1-adrenergic blocking agent prazosin at 10 nM and 30 nM concentration dependently. The contractile responses of the muscle to Expar were partly blocked after chemical sympathectomy of the preparations with 6-hydroxydopamine, and those obtained in the same conditions with tyramine were completely abolished, whereas responses to noradrenaline were unaffected by the 6-hydroxydopamine pretreatment. It is concluded that Expar contains principles, which can be characterized as direct and indirect sympathomimetic.

Adrenergic Agents↗

Neurofilament phosphorylation and axon diameter in the squid giant fibre system.

Electron energy loss spectroscopic analysis of squid giant axons in a phosphorus energy window yielded bright signals, which were shown to originate from highly phosphorylated neurofilaments. The frequency and distribution of these signals were analysed at defined intervals in cross-sections of the giant axon, starting from its origin in the stellate ganglion and extending distally along the stellar nerve. The analysis revealed a proximodistal gradient of increasing neurofilament phosphorylation. Within the stellate ganglion and for some distance beyond, the increase in frequency of signals correlated with the widening of the neurofilament meshwork and the radial growth of the axon. This agrees with the hypothesis that neurofilament phosphorylation regulates axon calibre by affecting interfilament spacing. In distal axon domains where the axon diameter diminished, contrary to expectations, the spacing of signals increased and the signals were significantly larger. Hyperphosphorylation apparently compensated for a diminishing supply of neurofilament protein. Contrary to predictions, the presynaptic terminal of the giant synapse contained a distinct and highly phosphorylated neurofilament meshwork. We conclude that the growth of the axon diameter is a function of neurofilament phosphorylation, interfilament spacing and neurofilament density. A mature and highly phosphorylated neurofilament cytoskeleton completely filled the presynaptic terminal of the giant synapse.

Animals↗

N-linked oligosaccharides can protect target cells from the lysis mediated by NK cells but not by cytotoxic T lymphocytes: role of NKG2-A.

We have previously shown that glycophorin A (GPA), inserted by electropulsation into the membrane of K562 cells, protected them from natural killer (NK) cell-mediated cytotoxicity and the unique N-linked oligosaccharide of GPA was essential for resistance to occur. The present study demonstrates that the protection level conferred by GPA is similar to the resistance induced by HLA-Cw3 expressed by transfected K562 cells. A monoclonal antibody against NKG2-A, an NK inhibitory receptor interacting with HLA class I antigens and belonging to the C-type lectin receptor, was able to restore the ability of NK cells to lyse K562 cells expressing HLA-Cw3 at the cell membrane but not electroinserted-GPA, suggesting that the N-linked oligosaccharide of GPA cannot be a ligand for NKG2-A. GPA was then electroinserted into the membrane of two lymphoblastoid B-cell lines: one was sensitive to NK cell-mediated lysis, the other was susceptible to cytotoxic CD8+ T-lymphocyte (CTL)-mediated cytotoxicity. The electroinserted GPA protected the target cells from NK-mediated cytotoxicity, whereas it did not modify the cell susceptibility to lysis by CTL. Endoglycosidase F treatment abolished the resistance towards NK cell-mediated lysis, suggesting that N-linked glycans could inhibit mechanisms used by NK cells to exert their cytotoxic function in agreement with our previous results.

Carbohydrate Conformation↗

No evidence for an involvement of alleles of polymorphisms in the serotonin1Dbeta and 7 receptor genes in obesity, underweight or anorexia nervosa.

The serotonergic (5-hydroxytryptamine, 5-HT) system has been implicated in body weight regulation and in the etiology of anorexia nervosa (AN). Here we describe the screening of the known Phe-124-Cys polymorphism in the 5-HT1Dbeta receptor gene and of the known Pro-279-Leu polymorphism in the 5-HT7 receptor gene. For association tests allele frequencies were compared between up to 393 extremely obese children and adolescents, 142 underweight students and 84 patients with AN. None of the association tests revealed nominal P-values below 0.3. We conclude that a major role of the investigated polymorphisms in body weight regulation or AN appears unlikely.

Adolescent↗

Serum leptin and gonadotropin levels in patients with anorexia nervosa during weight gain.

Leptin plays an important role in reproductive function. In patients with acute anorexia nervosa, serum leptin levels have repeatedly been shown to be lower than in age-matched controls. We have previously hypothesized that the amenorrhea characteristic of anorexia nervosa is related to this low leptin secretion. In an attempt to address this hypothesis, serum levels of leptin and follicle stimulating hormone (FSH) and luteinizing hormone (LH) of 16 female inpatients with anorexia nervosa or an eating disorder not otherwise specified (atypical anorexia nervosa) were measured on a biweekly basis during weight gain. We hypothesized that a serum leptin level of 1.85 microg L(-1) would be associated with gonadotropin levels at or above the minimal level observed during the menstrual cycle in healthy adult fertile females. Our results revealed that increments of LH levels generally tracked increments of leptin levels during the first weeks of treatment. Similarly, in those patients with low referral leptin levels, FSH initially also tracked leptin levels. In contrast, a relationship between gonadotropin levels and leptin secretion was no longer discernible after LH and FSH levels had peaked. Those patients with exceedingly low leptin levels upon admission revealed a slow increase of gonadotropin levels. Our hypothesis of a threshold leptin level of 1.85 microg L(-1) was supported for LH only.

Adolescent↗

Serum leptin levels, body fat deposition, and weight in females with anorexia or bulimia nervosa.

The objective of this retrospective study was to investigate the relation between serum leptin level and fat deposition in patients with eating disorders. 40 female inpatients with anorexia (n=24) or bulimia nervosa (n=16) were assessed for leptin level, body mass index (BMI), and percentage body fat by dual-energy X-ray absorbometry (DXA). The results show that percentage body fat is a better predictor for leptin level and clinical findings in eating disordered patients than BMI. We discuss the necessity for DXA measurements in anorectic patients for prognostic and research purposes.

Absorptiometry, Photon↗

Phenotypes in three pedigrees with autosomal dominant obesity caused by haploinsufficiency mutations in the melanocortin-4 receptor gene.

Recently, haploinsufficiency mutations in the melanocortin-4 receptor gene (MC4-R) were detected which were assumed to lead to the phenotype of extreme obesity. Previously, we detected three obese carriers among 306 index patients. Here we describe the detection of one haploinsufficiency carrier in an additional study group of 186 obese individuals. We subsequently genotyped and phenotyped 43 family members of these four index patients, two of whom were second-degree cousins. A total of 19 carriers were identified. Extreme obesity was the predominating phenotype. However, moderate obesity occurred in three of the carriers. No other specific phenotypic abnormalities were detected. Female haploinsufficiency carriers were heavier than male carriers in the respective families, a finding similar to findings in MC4-R-knockout mice. In conclusion, our data fully support the etiologic role of MC4-R haploinsufficiency mutations in obesity.

Adolescent↗

Basic mechanisms of monogenic inheritance.

To revive the appreciation of the importance of genetic studies for the understanding of neurologic diseases inherited in a monogenic fashion. After a description of the basic patterns of monogenic inheritance, the importance of linkage studies for the mapping of a disease gene is mentioned. Furthermore, the term linkage disequilibrium is introduced. Finally, several procedures used in current linkage analyses are briefly mentioned, with the aim of identifying the disease gene. The importance of genetic studies of disease families with many members, preferably from isolated surroundings to favor homogeneity, is stressed. However, such analyses can be performed only as a consequence of a close cooperation between clinicians and research scientists.

Animals↗

Threshold concentrations of endothelin-1: the effects on contractions induced by 5-hydroxytryptamine in isolated rat cerebral and mesenteric arteries.

This study compares the effects of threshold concentrations of endothelin-1 in isolated rat basilar arteries with those in mesenteric arterial branches and investigates the mechanisms of inhibitory and potentiating endothelin-1-effects. In basilar arteries, endothelin-1 reduces the contractions induced by 5-hydroxytryptamine (5-HT), by the thromboxane A2 agonist U46619, and by vasopressin. The inhibitory effect of endothelin-1 on the contraction induced by 5-HT is abolished by deendothelialization, by the endothelin ET(B) receptor antagonist RES 701-1, by indomethacin, or by glibenclamide. In mesenteric arteries, endothelin-1 potentiates the contractile effects of 5-HT, U46619, and vasopressin. The potentiation of the contractile effect induced by 5-HT is only somewhat modified by deendothelialization, but abolished by the thromboxane A2 receptor antagonists GR32191 and ridogrel. U46619 potentiates the 5-HT-effect in mesenteric arteries. Thus, though the contractile endothelin ET(A) receptors were not blocked, threshold concentrations of endothelin-1 inhibited contractile effects in the rat basilar artery via activation of endothelial ET(B) receptors. Prostaglandins and ATP-sensitive K+ channels are involved in this inhibitory action. In contrast, endothelin-1 potentiates contractile actions in mesenteric arteries via the release of endogeneous thromboxane A2 from non-endothelial cells. The study points out the completely different role of the endothelium in combined effects of endothelin-1 between cerebral and mesenteric arteries.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Necrotic tumor versus brain abscess: importance of amino acids detected at 1H MR spectroscopy--initial results.

PURPOSE: To assess the usefulness of the 0.9-ppm peak from amino acids (-CH3 moieties from valine, leucine, and isoleucine) for the differentiation of brain abscesses and tumors at in vivo hydrogen 1 magnetic resonance (MR) spectroscopy. MATERIALS AND METHODS: Amino acid concentrations were determined in vitro in 13 purulent samples from brain and nonbrain tissues and in nine aseptic fluids from necrotic brain tumors at two-dimensional (2D) 1H MR spectroscopy and liquid chromatography. Thirty-four patients with cystic intracerebral mass lesions (28 tumors, six abscesses) were examined at 1H MR spectroscopy in vivo. RESULTS: Amino acids were identified in vitro in both purulent and aseptic samples. Amino acid concentrations measured in the aseptic fluids at both liquid chromatography and 2D MR spectroscopy were far below the detection threshold of in vivo 1H MR spectroscopy. Quantitative results obtained at 2D MR spectroscopy showed no overlap in the ranges of amino acid concentrations in purulent and aseptic samples. In vivo, the proton spectra obtained with a 136-msec echo time (TE) revealed amino acids (inverted peak at 0.9 ppm) in only the abscesses. CONCLUSION: The detection of amino acid resonance at 0.9 ppm at in vivo 1H MR spectroscopy (136-msec TE) is a promising tool for distinguishing bacterial abscesses and cystic brain tumors.

Adolescent↗