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A Maier

Publications and source records attributed to A Maier.

At least 73 records · Page 4Linked to original sources
PubMed1999

Force field based conformational analysis of RNA structural motifs: GNRA tetraloops and their pyrimidine relatives.

The protocol of conformational analysis applied here to ribonucleotide oligomers combines conformational search in the space of torsion angles and energy minimization using the AMBER4.1 force field with a continuum treatment of electrostatic solute-solvent interactions. RNA fragments with 5'-GGGCGNNAGCCU-3' sequences commonly fold into hairpins with four-membered loops. The combinatorial search for acceptable conformations using the MC-SYM program was restricted to loop nucleotides and yielded roughly 1500 structures being compatible with a double-stranded stem. After energy minimization by the JUMNA program (without applying any experimental constraints), these structures converged into an ensemble of 74 different conformers including 26 structures which contained the sheared G-A base pair observed in experimental studies of GNRA tetraloops. Energetic analysis shows that inclusion of solvent electrostatic effects is critically important for the selection of conformers that agree with experimentally determined structures. The continuum model accounts for solvent polarization by means of the electrostatic reaction field. In the case of GNRA loop sequences, the contributions of the reaction field shift relative stabilities towards conformations showing most of the structural features derived from NMR studies. The agreement of computed conformations with the experimental structures of GAAA, GCAA, and GAGA tetraloops suggests that the continuum treatment of the solvent represents a definitive improvement over methods using simple damping models in electrostatic energy calculations. Application of the procedure described here to the evaluation of the relative stabilities of conformers resulting from searching the conformational space of RNA structural motifs provides some progress in (non-homology based) RNA 3D-structure prediction.

Base Sequence↗
PubMed1999

Self-expandable coated stent after intraluminal treatment of esophageal cancer: a risky procedure?

BACKGROUND: Stenting is a well established palliative treatment for stenotic malignant disease of the esophagus. Because of its merely mechanical potential other tumoricidal techniques are often done before stenting. METHODS: We did esophageal stenting in 11 patients (9 men and 2 women) using a self-expanding coated stent system. Three tumors were localized in the proximal, four in the middle, and four in the distal third of the esophagus. In 9 patients tumors were locally or functional nonresectable, 1 patient refused an operation, and 1 had a recurrence after esophagojejunostomy. One patient had had pretreatment by repetitive dilatation and local hyperthermia, 9 had had photodynamic therapy followed by endoluminal iridium 192 high-dose rate brachyradiotherapy, and 1 patient was admitted with esophagotracheal fistula. The interval between the last endoluminal treatment and stent insertion was between 3 and 29 days (mean, 11 days). RESULTS: In 7 patients (63.7%) no complications were observed. Four patients (36.3%) died of major complications within 1 week. Postmortem examination confirmed that the pressure of the fully expanding stent to the esophageal wall caused the rupture. CONCLUSION: The use of self-expanding coated stents in pretreated esophageal tumors is associated with a high risk of perforation due to pressure of the indwelling tube in a less resistant esophageal wall.

Adult↗
PubMed1999

Assessment of chronic constipation: colon transit time versus defecography.

OBJECTIVE: The aim of this study was to determine the value of radiological colon transit time (CTT) measurements in relation to defecography (DFG) in chronically constipated patients. MATERIALS AND METHODS: In 30 patients with chronic constipation, total and segmental CTT was determined using radiopaque markers. In all of these patients defecography (DFG) was obtained. The patients were divided into three groups: In group I, 11 patients were classified with idiopathic constipation based on low stool frequency, normal DFG, or absence of symptoms of abnormal defecation. In group II, ten patients with rectal intussusception were diagnosed by DFG. In group III, there were nine patients with rectal prolapse or spastic pelvic floor syndrome, based on results of DFG. RESULTS: Group I, idiopathic constipation (n = 11), showed increased total CTT (mean, 93 h) and segmental CTT (right colon, 33 h (36%), left colon, 31 h (33%), rectosigmoid, 29 h (31%)). In group II, intussusception (n = 10), patients had normal mean total CTT (54 h) and a relative decrease in rectosigmoid CTT (mean, 13 h (24%)). In group III (n =9), rectal prolapse (n = 5) or spastic pelvic floor syndrome (n = 4), patients showed elevated total (mean, 167 h) and rectosigmoidal CTT (mean, 95 h (57%)). Mean total CTT was significantly different between groups I and II and between groups II and III, and mean rectosigmoidal CTT was significantly different between all three groups (P < 0.05). CONCLUSION: The use of total and rectosigmoidal CTT helps to identify the underlying pathophysiology of chronic constipation. Furthermore CTT helps to identify patients, who may benefit from DFG.

Adult↗
PubMed1999

Effects of chronic alcohol abuse on duodenal mononuclear cells in man.

The aim of this study was to investigate whether chronic alcohol abuse alters the number and distribution of mononuclear cells of the duodenal mucosa. The number of common leukocyte antigen (CLA)-positive interepithelial lymphocytes (IEL), B lymphocytes (BL), IgA-producing plasma cells (IgA-PC), and macrophages (MP) was quantitatively evaluated in biopsies of the duodenal mucosa of patients with alcohol abuse compared to subjects without alcohol abuse. Biopsies from the descending part of the duodenum were obtained by endoscopy from two groups of patients with chronic alcohol abuse (group A1, abstinence <5 days, N = 21) and group A2 abstaining 5-10 days (N = 6). Twenty-five subjects without alcohol abuse served as controls (C). Immunohistochemical staining was done by avidin-biotin-complex method. In addition, the content of IgA in the plasma cells was determined by using a TV-densitometric method. The number of B-lymphocytes in the lamina propria was increased by 37% in group A1 (P < 0.005). A distinct decrease was observed in group A1 compared to C in the number of IEL that were CLA positive (-50%, P < 0.025) and in the number of macrophages (-54%, P < 0.025). In group A2 the differences in the number of B lymphocytes and macrophages were no longer seen. In A1, there was no significant change in the number of IgA-producing plasma cells or in the number of interepithelial lymphocytes counted after H&E staining compared to the controls. There was no difference in content of IgA in the IgA-producing plasma cells. From these results it is concluded that chronic alcohol abuse significantly influences the gut-associated immune system, possibly by increasing the permeability of the gut mucosa to macromolecules that act as antigens.

Alcoholism↗
PubMed1999

Biomolecular-chemical screening: a novel screening approach for the discovery of biologically active secondary metabolites. III. New DNA-binding metabolites.

Based on the chemical screening technique, biomolecular-chemical screening has been developed which makes use of two-dimensional TLC analysis of microbial extracts and combines thin-layer chromatography (RP-18) with binding studies towards DNA. In the first dimension the metabolites of the crude microbial extract are separated, and in the second dimension binding properties towards DNA are analysed. An initial screening program with 500 microbial extracts prepared by solid-phase extraction with XAD-16 resin resulted in 17 samples which contained metabolites with significant DNA-binding behavior. Fermentation, isolation and structural characterization led to already known metabolites [phenazine-1,6-dicarboxylate (1), phencomycin (2), 11-carboxy-menoxymycin B (3), soyasaponine I (4), and (8S)-3-(2-hydroxypropyl)-cyclohexanone (5)], as well as to new secondary metabolites. Fermentation of the producing organisms of the new DNA-binding metabolites, ent-8,8adihydro-ramulosin (6). (2R,4R)-4-hydroxy-2-(1,3-pentadienyl)-piperidine (7), (5R)-dihydro-5-pentyl-4'-methyl-4'-hydroxy-2(3H)-furanone (8), and seco-4,23-hydroxyoleane-12-en-22-one-3-carboxylic acid (9), as well as isolation, structural characterization, and physico-chemical properties are reported.

Chromatography, Thin Layer↗
PubMed1999

Biomolecular-chemical screening: a novel screening approach for the discovery of biologically active secondary metabolites. I. Screening strategy and validation.

Chemical screening using thin-layer chromatography and various staining reagents offers the opportunity to visualize an almost complete picture of a microbial secondary metabolite pattern (metabolic finger-print). A thorough application of this strategy resulted in a number of biologically active new secondary metabolites, although the screening strategy is per se not correlated to any biological activity. In the present paper we report on a novel approach called biomolecular-chemical screening which combines the chemical screening strategy with binding studies of biological relevance. Making use of thin-layer chromatography (TLC) and subsequent staining, biomolecular-chemical screening allows to examine binding properties of low molecular weight metabolites to certain bio-macromolecules. The screening strategy itself, as well as independent validation of the results using DNA as selected bio-macromolecule are presented. The biomolecular-chemical screening method is useful to screen binding behaviour towards DNA of both, pure metabolites by one-dimensional TLC, and crude extracts by two-dimensional TLC. Investigation of pure secondary metabolites as well as screening of crude microbial extracts and new secondary metabolites obtained with this screening strategy are presented in accompanying papers.

Bacteria↗
PubMed1999

Biomolecular-chemical screening: a novel screening approach for the discovery of biologically active secondary metabolites. II. Application studies with pure metabolites.

The novel screening strategy called "biomolecular-chemical screening" combines the advantages of the chemical screening approach--the analysis of the chromatographic and chemical behaviour of secondary metabolites on TLC plates--with binding studies of these molecules with bio-macromolecules like DNA. This approach was advantageously used to detect the interaction of pure compounds with DNA. In order to prove the reliability of the biomolecular-chemical screening and to examine DNA-binding properties, 470 pure secondary metabolites were analysed by this method. Besides the confirmation of already known binders with the TLC-based method, for a number of natural products DNA-binding properties were discovered for the first time. In consequence, binding of pure compounds can be measured by 1D TLC in a reliable and easy manner, in which DNA is applied together with the test compound at the starting spot. Analysis is performed via differences in Rf-values in comparison to a reference chromatogram without DNA.

Bacteria↗
PubMed1999

[Rectal carcinoma--optimizing therapy by improved preoperative staging? Is endosonography required?].

Endosonography is superior to other imaging modalities (CT, MRI) and has to be considered as the most useful and accurate method in staging rectal carcinoma inclusive the invasion of the sphincter apparatus. Selection of patients for sphincter saving operation, local excision and in case of preoperative adjuvant therapy is greatly supported by endosonography and has to be considered as inevitable in the preoperative management.

Endosonography↗
PubMed1998

Proportions of slow-twitch and fast-twitch extrafusal fibers in receptive fields of tendon organs in chicken leg muscles.

Golgi tendon organs are mechanoreceptors that monitor the contractile force produced by motor units. Receptors are most responsive to contractions of extrafusal muscle fibers that terminate closest to them and on them. Three anterior and four posterior chicken leg muscles were examined. Proportions of immunohistochemically identified slow-twitch extrafusal fibers and fast-twitch extrafusal fibers were calculated for 374 tendon organ receptive fields. Tendon organs were observed in muscle regions occupied either by slow-twitch fibers or fast-twitch fibers only, but most were found in regions that contained both slow-twitch and fast-twitch extrafusal fibers. The frequency with which each fiber type occurred near tendon organs approached the frequency with which it occurred in more inclusive regions. In receptive fields with mixed fiber populations, fast-twitch fibers were the predominant type, especially in the anterior leg muscles. Distribution patterns of extrafusal fiber types adjacent to and farther removed from tendon organs suggest that afferent discharges from tendon organs are by and large unbiased measures of the contractile activity of the extrafusal fiber population of the muscle portion in which the tendon organs are located. In mixed muscle regions, slow-twitch fibers and fast-twitch fibers attach on given tendon organs, enabling them to monitor forces produced by slow motor units and by fast motor units. Most tendon organs are situated in mixed extrafusal fiber fields with high fast-twitch fiber content, indicating that in chicken leg muscles sensory feedback from tendon organs is largely one from fast motor units.

Animals↗
PubMed1998

Boron tolerable intake: re-evaluation of toxicokinetics for data-derived uncertainty factors.

Boron, which is ubiquitous in the environment, causes developmental and reproductive effects in experimental animals. This observation has led to efforts to establish a Tolerable Intake value for boron. Although risk assessors agree on the use of fetal weight decreases observed in rats as an appropriate critical effect, consensus on the adequacy of toxicokinetic data as a basis for replacement of default uncertainty factors remains to be reached. A critical analysis of the existing data on boron toxicokinetics was conducted to clarify the appropriateness of replacing default uncertainty factors (10-fold for interspecies differences and 10-fold for intraspecies differences) with data-derived values. The default uncertainty factor for variability in response from animals to humans of 10-fold (default values of 4-fold for kinetics and 2.5-fold for dynamics) was recommended, since clearance of boron is 3- to 4-fold higher in rats than in humans and data on dynamic differences--in order to modify the default value--are unavailable. A data-derived adjustment of 6-fold (1.8 for kinetics and 3.1 for dynamics) rather than the default uncertainty factor of 10-fold was considered appropriate for intrahuman variability, based on variability in glomerular filtration rate during pregnancy in humans and the lack of available data on dynamic differences. Additional studies to investigate the toxicokinetics of boron in rats would be useful to provide a stronger basis for replacement of default uncertainty factors for interspecies variation.

Animals↗
PubMed1998

Role of magnetic resonance imaging in renal transplant recipients with acquired cystic kidney disease.

OBJECTIVES: To evaluate the impact of magnetic resonance imaging (MRI) in renal transplant recipients whose ultrasound (US) examinations of the native kidneys have met the criteria of acquired cystic kidney disease (ACKD). METHODS: The US scans of 840 renal allograft recipients were prospectively studied. In addition, 46 of 169 patients diagnosed with ACKD by US scans underwent MR examination. MRI protocols included (a) T1 and T2-weighted fast spin echo imaging, (b) T2-weighted gradient echo imaging, and (c) gadolinium-enhanced T1-weighted imaging in 7 patients with evidence of complex cysts. In the case of complex lesions, both US and MRI follow-up examinations were performed between 6 and 12 months after the prior examination. RESULTS: US examination showed ACKD in 169 of 840 patients. In addition, US revealed 8 patients with renal cell carcinomas (RCC). Of these 8 patients, 7 had evidence of ACKD. The median number of cysts depicted on US examination in native kidneys of renal transplant recipients was 3 (range 0 to 10) on both sides. MRI revealed significantly more and smaller cysts compared to US. The median number of cysts was seven on the left and nine on the right native kidneys, respectively. MRI revealed 18 complex lesions in 7 patients. Thirteen of 18 complex lesions were undetected by US. CONCLUSIONS: MRI is superior to US in depiction of simple and complex lesions of native kidneys in renal allograft recipients. MRI exhibits no overestimation of the prevalence of ACKD on the basis of the US criteria already mentioned. Advantages of MRI do not justify routine screening tests by this imaging modality. However, MRI should be used for further evaluation of complex lesions detected by US.

Adult↗
PubMed1998

Is aggressive surgery in pleural empyema justified?

OBJECTIVE: High risk and a long hospitalization time are often quoted as negative aspects of aggressive surgery in pleural empyema. We did a retrospective analysis evaluating outcome and duration of hospitalization in patients treated according to an aggressive schedule. METHODS: Since 1989 we have treated 101 patients with pleural empyema (72 males, 29 females; mean age 50.3 years, range 11-91 years; 77 metapneumonic empyema, 24 empyema following trauma or abdominal surgery). Sixty-nine patients had had unsuccessful conservative pre-treatment (antibiotics, thorcozentses, drainage/irrigation, VATS). Thirty-one were critically ill patients. In eight cases a seropurulent stage of empyema was present, 17 patients had fibrinous membranes, 30 an organizing stage with and 46 without well identifiable dissection plane. Eighty-five patients proceeded to thoracotomy. Pulmonary abscesses or indurative pneumonia necessitated wedge-resection, lobectomy, or pneumonectomy in 29 cases. In the presence of gross necroses or callosities not amenable to decortication primary open-window thoracostomy (n = 22) was carried out. In six cases a secondary open-window thoracostomy was carried out because of persisting putrid secretion and sepsis persisting after decortication or after drainage. The thoracostomy was closed when clean granulative tissue developed. Sixteen patients underwent only drainage and irrigation because of an early stage or because of a general condition not permitting thoracotomy. RESULTS: Three patients died due to severe sepsis not responding to treatment, one had fatal bleeding from a duodenal ulcer (mortality rate 3.9%). The others were able to resume their preoperative activities. The median duration of hospitalization was 14 days (mean 21.1 days; SEM 1.7 days). CONCLUSION: Aggressive surgery for pleural empyema beyond the seropurulent stage ensures rapid relief from sepsis at a low mortality rate even in very ill patients.

Chest Tubes↗
PubMed1998

[Prevalence of abdominal aortic aneurysms: a sonographic screening study].

PURPOSE: To determine the prevalence of abdominal aortic aneurysms (AAA) in males above 60 years of age. METHODS: 1043 males of 60 years of age or older underwent sonographic examinations of the abdominal aorta. All of the candidates had volunteered for the examination, and special care was taken to avoid preselection of the candidates. Wherever possible, information was obtained on the following risk factors: cholesterol level, nicotine, diabetes, insulin and other medication, hypertonia and cardiac risk. RESULTS: An AAA was diagnosed in 2.59% of the cases, while ectasia of the abdominal aorta was detected in 11.89%. The mean diameter of the aneurysms was 39.1 mm. Significant correlations between the various risk factors and abnormalities of the abdominal aorta could be established in patients suffering from angina pectoris (p = 0.004) and from congestive heart failure (p = 0.014). CONCLUSIONS: AAA in males above 60 occurs in 2,590 out of 100,000 cases. The most noteworthy risk factors in the development of AAA are cardiovascular disorders.

Age Factors↗
PubMed1998

Sensory innervation of myosin heavy chain-based types of chicken intrafusal fiber.

Chicken intrafusal fibers that had been categorized as slow or fast contracting by their reactions with monoclonal antibodies against myosin heavy chains (MHC) at polar regions were examined at the equator and neighboring juxtaequator to determine if fiber type-specific morphologies were also present at the sensory region. The parameters chosen for examination were contractile filaments, distribution of acetylcholinesterase and sensory innervation. Evaluation of acetylcholinesterase was included to define the proximal limit of motor terminal distribution. At the equator actin was primarily restricted to a thin layer beneath myosensory junctions. Myosin heavy chains at the equator and the juxtaequator were more evenly distributed. Although absent from the synaptic side of the sensory region, acetylcholinesterase activity was present on the extrasynaptic side. Plots of diameters of sensory axon collaterals and of sensory endings yielded continuous spectra instead of distinct peaks. Taken together, these features indicated a uniform equatorial morphology. However, sensory terminals to fast intrafusal fibers were longer and narrower than those to slow intrafusal fibers, and typically more terminals impinged on fast than on slow intrafusal fibers. Moreover, in the larger spindles short sensory terminals were most prevalent near the equatorial-juxtaequatorial junction, the region where in mammalian intrafusal fibers secondary sensory axons make contact. The differences seen in sizes and distributions of terminals suggest that, despite the lack of type-specific morphologies at the sensory region of chicken intrafusal fiber types, some level of functional separation is maintained there.

Animals↗
PubMed1998

Aromatic hydrocarbon receptor polymorphism: development of new methods to correlate genotype with phenotype.

Differential CYP1A1 inducibility, reflecting variations in aromatic hydrocarbon receptor (AHR) affinity among inbred mouse strains, is an important determinant of environmental toxicity. We took advantage of the Ahr polymorphism in C57BL/6 and DBA/2 mice to develop an oligonucleotide-hybridization screening approach for the rapid identification of DNA sequence differences between Ahr alleles. Oligonucleotides containing single-base changes at polymorphic sites were immobilized on a solid support and hybridized with C57BL/6 or DBA/2 AHR cDNA radiolabeled probes. The observed hybridization patterns demonstrate that this approach can be used to detect nucleotide differences in the Ahr coding region with very high accuracy. In parallel experiments, we used a yeast two-hybrid system to assess phenotypic differences in AHR function. AHR activation, as measured by beta-galactosidase reporter activity in Saccharomyces cerevisiae strain SFY526, was determined following treatment with varying doses of the AHR ligand beta-naphthoflavone (BNF). We found that the C57BL/6 AHR has about a 15-fold higher affinity for BNF than the DBA/2 AHR, in much better agreement with results reported for whole-animal studies than the values observed by in vitro ligand-binding assays. Using C57BL/6 and DBA/2 AHR chimeric proteins, we also confirmed the previously reported observation that an A375V change is principally responsible for the high- to low-affinity AHR phenotype. There has been no straightforward method to reliably and reproducibly phenotype large numbers of humans for CYP1A1 inducibility or AHR affinity. Screening human AHR cDNAs by oligonucleotide-hybridization and yeast two-hybrid methodologies will be invaluable for the rapid and unequivocal determination of changes in DNA sequence and receptor-ligand affinities associated with human AHR polymorphisms.

Animals↗
PubMed1997

Histologic liver abnormalities in an autopsy series of patients with rheumatoid arthritis.

A retrospective review was performed on 188 autopsied cases of rheumatoid arthritis at our institutions during 1958-1985, prior to the widespread use of methotrexate. Hepatic histology was reported in 182 cases. All available microscopic liver slides from cases in which the autopsy report described portal tract inflammation, fibrosis, cirrhosis, tumour, amyloid, vasculitis, or infections involving the liver were examined and graded by a hepatic pathologist blinded to the original diagnosis, along with a representative sample of cases with reports describing fatty change or no hepatic pathologic abnormalities. Ninety normal and abnormal cases were reviewed from the 182 for which hepatic histology was available. Fifteen cases of diffuse fibrosis were identified upon blinded review. Two cases were graded as severe fibrosis (grades 3 or 4 on a scale of 0-4) without an identifiable pathologic cause, in both of which the liver disease was suspected premortem (alcohol abuse and viral hepatitis). Although the incidence of fibrosis in this series is slightly higher than that previously described, serious fibrotic liver disease was rare. These results support the current practice of limiting pre-treatment liver biopsies prior to methotrexate therapy to patients with suspected liver disease.

Adult↗