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Biomedical subjects

P Wagner

Publications and source records attributed to P Wagner.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Therapy of the adrenocortical carcinoma with Lysodren (o,p'-DDD). Therapeutic management by monitoring o,p'-DDD blood levels].

BACKGROUND: o,p'-DDD (1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)-ethane), which leads to a cytotoxic necrosis of the adrenal glands, currently is therapy of choice for metastasized adrenocortical carcinomas. Clinical experience is still poor, but most studies demonstrate an increment of survival time in patients treated with o,p'-DDD after incomplete surgery. The therapeutic range is close and therefore dosage is difficult, mainly based on clinical signs. Methods for routine determination of o,p'-DDD are not yet broadly available. PATIENTS AND METHOD: We developed a method for the determination of o,p'-DDD and report our experience with the monitoring of serum levels of o,p'-DDD in our patients. Nine patients have been included, eight patients with metastasized adrenocortical carcinoma were treated with o,p'-DDD. RESULTS: At time of evaluation six of eight patients had deceased, 27.9 +/- 25.1 months after recurrence of the disease. Time of survival for all patients was 28.2 +/- 22.0 months since diagnosis of recurrence. In three patients the target dose of 9-10 g/d could not be reached due to the clinical situation. The serum levels of these patients were low (6.3 +/- 4.2 micrograms/ml). Mean survival time was significantly longer for those patients who reached serum levels above 14 micrograms/ml in comparison to those who failed to reach such high levels (41.3 +/- 16.2 vs 6.3 +/- 3.6 months, p < 0.01). The dose which was necessary to reach high levels was individually different. All patients developed adrenocortical insufficiency. Other side effects were fatigue (seven patients), gastrointestinal problems and elevated liver enzymes (six patients each), changes in blood count (five patients) and central nervous disorder (four patients). All patients developing intolerable side effects had very high serum levels of o,p'-DDD (> 20 micrograms/ml). CONCLUSIONS: Our data confirm that the efficacy of a therapy with o,p'-DDD as well as the risk to develop intolerable side effects depend on the serum levels of o,p'-DDD. Monitoring of o,p'-DDD therapy by measuring serum levels of o,p'-DDD helps to adapt this therapy individually, avoiding serious side effects as well as to realize antitherapeutical resistance. Determination of o,p'-DDD serum levels helps to decide over intensification or cessation of therapy.

Adrenal Cortex Neoplasms↗
PubMed2001

Monolayers of derivatized poly(L-lysine)-grafted poly(ethylene glycol) on metal oxides as a class of biomolecular interfaces.

We report on the design and characterization of a class of biomolecular interfaces based on derivatized poly(l-lysine)-grafted poly(ethylene glycol) copolymers adsorbed on negatively charged surfaces. As a model system, we synthesized biotin-derivatized poly(l-lysine)-grafted poly(ethylene glycol) copolymers, PLL-g-[(PEGm)((1-x)) (PEG-biotin)(x)], where x varies from 0 to 1. Monolayers were produced on titanium dioxide substrates and characterized by x-ray photoelectron spectroscopy. The specific biorecognition properties of these biotinylated surfaces were investigated with the use of radiolabeled streptavidin alone and within complex protein mixtures. The PLL-g-PEG-biotin monolayers specifically capture streptavidin, even from a complex protein mixture, while still preventing nonspecific adsorption of other proteins. This streptavidin layer can subsequently capture biotinylated proteins. Finally, with the use of microfluidic networks and protein arraying, we demonstrate the potential of this class of biomolecular interfaces for applications based on protein patterning.

Binding Sites↗
PubMed2001

[Optic nerve evulsion: Metaanalysis].

BACKGROUND: Evulsion of the optic nerve is a rare form of traumatic optic neuropathy. It is a rupture of the optic nerve at the disc without damage of its sheaths occurring in association with a blunt skull trauma or a blunt bulbar trauma. MATERIAL AND METHODS: We searched the literature using Medline database for all articles with evulsion of the optic nerve. The bibliographies of the papers found therein were used to get a complete review. The data were analyzed with special regard to age, sex, mechanism of injury, and (if available) defects of visual field. RESULTS: Sixty-three patients with a mean age of 22 years (range 4 to 60 years) were included in the study. In 22 patients (35 %) a partial and in 41 patients (65 %) a complete evulsion was present. In 31 patients (49 %) the cause was a small blunt object or finger that stroke the eye or entered the orbita. In 19 patients (30 %) a severe blunt skull trauma had occurred. The analysis of visual fields in eyes with partial evulsion of the optic nerve revealed a defect in the superior visual field in 6 of 12 patients and a defect in the inferonasal visual field in 3 of 12 patients. PATHOGENESIS: Our review suggests that the most common mechanism of injury is a severe rotation of the eye leading to rupture of the optic nerve fibers and an anterior displacement of the bulbus, possibly with deformation of the posterior eye walls.

Adolescent↗
PubMed2001

Two 1-substituted 4-nitroimidazoles.

Crystalline 4-nitro-1-phenylimidazole, C9H7N3O2, (I), and 4'-nitro-1-phenyl-4,1'-biiimidazole, C12H9N5O2, (II), contain C-H...O and C-H...N hydrogen bonds, connecting the molecules into infinite chains. The aromatic fragments in both compounds are nearly planar. The dihedral angles between the benzene and imidazole rings are 26.78 (5) degrees in (I) and 29.36 (8) degrees in (II).

Crystallography, X-Ray↗
PubMed2000

p-hydroxyphenylacetaldehyde, an aldehyde generated by myeloperoxidase, modifies phospholipid amino groups of low density lipoprotein in human atherosclerotic intima.

Oxidation of low density lipoprotein (LDL) may be of critical importance in the pathogenesis of atherosclerosis. Recent studies suggest that oxidized phospholipids render LDL atherogenic. However, both the structures and the physiologically relevant pathways for the formation of modified phospholipids in oxidized LDL remain poorly understood. We previously showed that p-hydroxyphenylacetaldehyde (pHA) is the major product of L-tyrosine oxidation by the myeloperoxidase/hydrogen peroxide/chloride system of phagocytes. In the current studies, we demonstrate that this reactive aldehyde targets the aminophospholipids of LDL in vitro and in vivo. Activated human neutrophils generated pHA-ethanolamine, the reduced adduct of pHA with the amino group of phosphatidylethanolamine, on LDL phospholipids by a reaction that required myeloperoxidase, H(2)O(2), and L-tyrosine. The cellular system could be replaced by HOCl and L-tyrosine but not by a wide variety of other oxidation systems, indicating that pHA-ethanolamine is a specific marker for covalent modification of aminophospholipids by myeloperoxidase. To determine whether aldehydes modify aminophospholipids in vivo, we quantified levels of pHA-ethanolamine in acid hydrolysates of reduced lipid extracts through isotope dilution gas chromatography/mass spectrometry. Circulating LDL contained undetectable levels of pHA-modified phospholipid (<0.1 mmol/mol). In contrast, the concentration of pHA-ethanolamine in LDL isolated from human atherosclerotic lesions was strikingly elevated (4.5 mmol/mol). Collectively, these results demonstrate a novel, myeloperoxidase-based mechanism for modifying the amino group of LDL phospholipids. They also offer the first evidence that myeloperoxidase may damage LDL lipids in vivo, raising the possibility that aldehyde-modified aminophospholipids play a role in inflammation and vascular disease.

Acetaldehyde↗
PubMed2000

Function, oligomerization, and conformation of tumor-associated p53 proteins with mutated C-terminus.

Mutations that affect the oligomerization domain (OD) of the p53 tumor suppressor may be of particular interest because of the remarkable contradiction between the conservation of the OD and its relative functional resistance to amino acid substitutions, and because of recent hints that cellular protein factors may interact with the OD. Both point to the possibility that this domain fulfills tasks beyond oligomerization. We report that the tumor-associated mutants 330H, 334V, and 337C are defective for homo-oligomerization by three criteria. Accordingly, 330H and 337C failed to bind to a p53 recognition motif in gel-shift assays and to stimulate reporter genes efficiently in transient transfections. 334V retained some activity in both assays despite being oligomerization-defective. The ability of the mutants to induce apoptosis correlated with their performance in the DNA binding and transactivation assays. However, mutants 330H and 337C were able to provoke cell death when overexpressed, which in combination with their failure to transactivate genes suggests competence for the induction of transactivation-independent apoptosis at high protein levels. Although 334V and 337C failed to homo-oligomerize, they were able to hetero-oligomerize with a p53 with wild-type OD, and 334V was able to interfere with transactivation by wt p53. All mutants showed a reduced reactivity with antibody PAb421 and a distinct calpain cleavage pattern indicative of conformational alterations. In conclusion, tumor-associated OD mutants of p53 can be functionally competent to different degrees despite of being oligomerization defective.

Antibodies↗
PubMed2000

[Merkel cell tumor of the eyelids: review of the literature and report of 2 patients].

BACKGROUND: The Markel cell carcinoma is a rare malignant skin tumor. The tumor was first described in 1972 by Toker and he named it trabecular carcinoma. We had the opportunity to treat two patients with a Merkel cell carcinoma of the upper and lower eyelid and reviewed the literature using the "Medline" database concerning Merkel cell carcinomas of the ocular adnexa. HISTORY AND SIGNS: A 76-year-old female patient was referred to our hospital because of an inflammatory tumor of the left upper eyelid present for two months. A 91-year-old male patient noticed for four weeks a painless itching lesion at the left lower eyelid. The remaining ophthalmologic examination in these patients was unremarkable. THERAPY AND OUTCOME: Both tumors were excised. Histological and immunohistochemical examination verified a Merkel cell carcinoma in both cases. The 76-year-old female patient exhibited no recurrent tumor after a follow-up of 18 months. The 91-year-old male patient had a recurrent tumor inferior to the temporal lower eyelid 7 months after tumor excision, however, lymph node metastasis is not present as of yet. The patient underwent radiation therapy with cobalt of the left orbit with a total dose of 60 Gy. CONCLUSION: Merkel cell carcinomas can occur everywhere on the skin; the eyelids are affected in 10% of all cases. Best histochemical markers are cytokeratin 20 and neurospecific enolase. A review of the literature revealed 31 patients with Merkel cell carcinomas involving the eyelids. Female patients were more often affected than male patients. The upper eyelid was more frequently involved than the lower eyelid. Recurrent disease is frequent.

Aged↗
PubMed2000

Integrating ambiguously aligned regions of DNA sequences in phylogenetic analyses without violating positional homology.

Phylogenetic analyses of non-protein-coding nucleotide sequences such as ribosomal RNA genes, internal transcribed spacers, and introns are often impeded by regions of the alignments that are ambiguously aligned. These regions are characterized by the presence of gaps and their uncertain positions, no matter which optimization criteria are used. This problem is particularly acute in large-scale phylogenetic studies and when aligning highly diverged sequences. Accommodating these regions, where positional homology is likely to be violated, in phylogenetic analyses has been dealt with very differently by molecular systematists and evolutionists, ranging from the total exclusion of these regions to the inclusion of every position regardless of ambiguity in the alignment. We present a new method that allows the inclusion of ambiguously aligned regions without violating homology. In this three-step procedure, first homologous regions of the alignment containing ambiguously aligned sequences are delimited. Second, each ambiguously aligned region is unequivocally coded as a new character, replacing its respective ambiguous region. Third, each of the coded characters is subjected to a specific step matrix to account for the differential number of changes (summing substitutions and indels) needed to transform one sequence to another. The optimal number of steps included in the step matrix is the one derived from the pairwise alignment with the greatest similarity and the least number of steps. In addition to potentially enhancing phylogenetic resolution and support, by integrating previously nonaccessible characters without violating positional homology, this new approach can improve branch length estimations when using parsimony.

Alligators and Crocodiles↗
PubMed2000

Human sleep EEG under the influence of pulsed radio frequency electromagnetic fields. Results from polysomnographies using submaximal high power flux densities.

Former exploratory investigations of sleep alterations due to global system for mobile communications (GSM) signals have shown a hypnotic and REM-suppressive effect under field exposure. This effect was observed in a first study using a power flux density of 0.5 W/m(2), and the same trend occurred in a second study with a power flux density of 0.2 W/m(2). For the present study, we applied a submaximal power flux density of 50 W/m(2). To investigate putative effects of radio frequency electromagnetic fields (EMFs) of cellular GSM phones on human sleep EEG pattern, all-night polysomnographies of 20 healthy male subjects both with and without exposure to a circularly polarized EMF (900 MHz, pulsed with a frequency of 217 Hz, pulse duration 577 microseconds) were recorded. The results showed no significant effect of the field application either on conventional sleep parameters or on sleep EEG power spectra.

Adaptation, Physiological↗
PubMed2000

Maternal drug abuse and human term placental xenobiotic and steroid metabolizing enzymes in vitro.

We evaluated the impact of maternal drug abuse at term on human placental cytochrome P450 (CYP)-mediated (Phase I) xenobiotic and steroid-metabolizing activities [aromatase, 7-ethoxyresorufin O-deethylase (EROD), 7-ethoxycoumarin O-deethylase (ECOD), pyrene 1-hydroxylase (P1OH), and testosterone hydroxylase], and androstenedione-forming isomerase, NADPH quinone oxidoreductase (Phase II), UDP-glucuronosyltransferase (UGT), and glutathione S-transferase (GST) activities in vitro. Overall, the formation of androstenedione, P1OH, and testosterone hydroxylase was statistically significant between control and drug-abusing subjects; we observed no significant differences in any other of the phase I and II activities. In placentas from drug-abusing mothers, we found significant correlations between ECOD and P1OH activities (p < 0. 001), but not between ECOD and aromatase or P1OH and EROD activities; we also found significant correlations between blood cotinine and UGT activities (p < 0.01). In contrast, in controls (mothers who did not abuse drugs but did smoke cigarettes), the P1OH activity correlated with ECOD, EROD (p < 0.001), and testosterone hydroxylase (p < 0.001) activities. Our results (wider variation in ECOD activity among tissue from drug-abusing mothers and the significant correlation between P1OH and ECOD activities, but not with aromatase or EROD activities) indicate that maternal drug abuse results in an additive effect in enhancing placental xenobiotic metabolizing enzymes when the mother also smokes cigarettes; this may be due to enhancing a "silent" CYP form, or a new placental CYP form may be activated. The change in the steroid metabolism profile in vitro suggests that maternal drug abuse may alter normal hormonal homeostasis during pregnancy.

Adult↗
PubMed2000

Multiple endocrine neoplasia type 1 (MEN1) gene mutations in a subset of patients with sporadic and familial primary hyperparathyroidism target the coding sequence but spare the promoter region.

Germ line mutations of the multiple endocrine neoplasia type 1 (MEN1) tumour suppressor gene cause MEN1, a rare familial tumour syndrome associated with parathyroid hyperplasia, adenoma and hyperparathyroidism (HP). Here we investigated the role of the MEN1 gene in isolated sporadic and familial HP. Using RT-PCR single-strand conformational polymorphism screening, somatic (but not germ line) mutations of the MEN1 coding sequence were identified in 6 of 31 (19.3%) adenomas from patients with sporadic primary HP, but none in patients (n=16) with secondary HP due to chronic renal failure. MEN1 mutations were accompanied by a loss of heterozygosity (LOH) for the MEN1 locus on chromosome 11q13 in the adenomas as detected by microsatellite analysis. No DNA sequence divergence within the 5' region of the MEN1 gene, containing the putative MEN1 promoter, was detectable in HP adenomas. Clinical characteristics were not different in HP patients with or without MEN1 mutation. Heterozygous MEN1 gene polymorphisms were identified in 9.6% and 25% of patients with primary and secondary HP respectively. In a large kindred with familial isolated familial HP, MEN1 germ line mutation 249 del4 and LOH was associated with the HP phenotype and a predisposition to non-endocrine malignancies. We suggest that the bi-allelic somatic loss of MEN1 wild-type gene expression is involved in the pathogenesis of a clinically yet undefined subset of sporadic primary HP adenomas. MEN1 genotyping may further help define the familial hyperparathyroidism-MEN1 disease complex, but it seems dispensable in sporadic primary HP.

Adenoma↗
PubMed2000

An additional transcript of the cdc25C gene from A431 cells encodes a functional protein.

Human p53 protein was found to be functional in fission yeast in terms of growth repression and checkpoint control. Expression of wild-type p53 or the hot spot mutant p53His273 results in dramatic morphological changes and loss of viability of recipient yeast cells. Overexpression of cdc25C phosphatase, the mitotic activator of cdc2, results in suppression of a p53-induced growth arrest. In order to understand the interplay between p53 and cdc25C in mammalian cells we isolated and sequenced cdc25C cDNA from the epidermoid carcinoma cell line A431, which is known to carry the p53His273 mutation. Two different transcripts of the human cdc25C gene were detected by RT-PCR analysis - one full-length transcript and a shortened version (cdc25Cdm) that carries two deletions in the 5'-region of the gene. In normal human skin fibroblasts only one full-length cdc25C transcript was detected. The two different transcripts code for proteins with a molecular weight of 55 kDa and 46 kDa, respectively. Both cdc25C cDNAs from A431 cells were found to complement a conditional lethal cdc25.22 mutant strain as well as a cdc25 deletion strain of Schizosaccharomyces pombe indicating that functional proteins were translated. Expression of cdc25Cdm variant leads to a stronger uncoupling of DNA replication from mitosis than expression of cdc25C suggesting that the deletion within the amino-terminus of cdc25C leads to a protein which might contribute some potential for oncogenic transformation. As with cdc25C, uncoupling of the DNA synthesis checkpoint by cdc25Cdm was reversed by coexpression of wild-type p53.

Alternative Splicing↗
PubMed2000

[Influence of diagnostic tests for estimating prevalence during surveillance programs].

The influence of diagnostic tests on the estimation of the prevalence and the calculation of sample sizes with respect to different sampling schemes are presented in this paper. These sampling schemes are used for the implementation of surveillance programs. Assuming "perfect tests" (i.e. sensitivity = specificity = 100%) the calculated sample sizes, e.g. for an IBR/IPV-surveillance or a paratuberculosis survey, are half of the sample sizes considering sensitivity and specificity of the diagnostic tests. However the probability not to identify infected livestocks may be 4 times higher neglecting the test characteristics and assuming perfect tests.

Animal Diseases↗
PubMed2000

[Doctors and apothecaries as botanists in the renaissance].

It is often claimed, that the late attempts in the renaissance to classify plants according to Aristotelian principles were caused by insufficient morphological knowledge and terminology, by problems with identification of the plants described by the ancient authorities and by the overwhelming number of new plants from the hitherto unknown parts of the world. These explanations are in the present paper not contested but supplemented with information achieved by analysis of two dialogues on botanical problems, both published in the 1530s, in which the ambiguities of the then new science are discussed. The main object of the studies in botany made by medical doctors was identification of simplicia in the pharmacies and drug-dealers shops. Control of the simplicia sold was a public duty demanded of university professors and medical doctors, and the teaching in plant science consequently concentrated on parmacognosy. As even the best Aristotelian classification is useless in identification of small plant parts, systematic botany in the modern sense was not needed and it is concluded that this fact also contributed to the late interest in classification.

Botany↗
PubMed1999

Two outbreaks of multidrug-resistant Salmonella serotype typhimurium DT104 infections linked to raw-milk cheese in Northern California.

CONTEXT: Salmonella serotype Typhimurium definitive type 104 (DT104), with resistance to 5 drugs (ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracycline), has emerged as the most common multidrug-resistant Salmonella strain in the United States. However, illnesses resulting from this strain have not been associated definitively with a source in this country. OBJECTIVE: To determine the source of 2 outbreaks of Salmonella Typhimurium DT104. DESIGN: Matched case-control study conducted between March 24 and April 5, 1997 (outbreak 1), enhanced surveillance for new cases dating from February 1, 1997 (outbreak 2), and environmental and laboratory investigations. SETTING AND PARTICIPANTS: The case-control study included residents of 2 adjacent counties in northern California infected with the outbreak strain of Salmonella Typhimurium var Copenhagen and age-matched controls. For enhanced surveillance, a case was defined as Salmonella Typhimurium infection in a person exposed to fresh Mexican-style cheese. MAIN OUTCOME MEASURES: Risk factors for infection and source of implicated food. RESULTS: Outbreak 1 peaked in February 1997; 31 patients were confirmed by culture as having Salmonella Typhimurium var Copenhagen infection, isolates of which showed indistinguishable pulsed-field gel electrophoresis (PFGE) patterns. The outbreak strain was phage type DT104 with the 5-drug resistance pattern. Sixteen cases and 25 controls were enrolled in the case-control study; 15 of 16 Salmonella Typhimurium var Copenhagen cases compared with 14 of 24 matched controls reported eating unpasteurized Mexican-style cheese, (matched odds ratio, 7.9; 95% confidence interval, 1.1-354.9). Enhanced surveillance uncovered outbreak 2, which peaked in April 1997 and was caused by a non-Copenhagen variant of Salmonella Typhimurium. During outbreak 2, Salmonella Typhimurium was isolated from 79 persons who ate fresh Mexican-style cheese from street vendors and from cheese samples and raw milk. The PFGE pattern of the milk isolate matched 1 of the 3 patterns recovered from patients; all strains were phage type DT104b with the 5-drug resistance pattern. CONCLUSION: Raw-milk products pose a risk for multidrug-resistant Salmonella Typhimurium DT104 infections.

Adolescent↗
PubMed1999

[Ultrasound biomicroscopy in iris lesions].

INTRODUCTION: It is difficult to classify lesions of the iris, especially when they are posterior or in the iridociliary angle of the eye. METHOD: We used an ultrasound biomicroscope (Humphrey, Zeiss, Oberkochen, Germany) with a high-frequency sound head (30 and 50 Hz). This study included all patients with unspecified iris processes who were examined at the University Eye Clinic and Hospital of Ulm between September 1996 and February 1997. Fifteen patients, aged between 9 to 82 years (average age = 48.9 years), were prospectively evaluated. RESULTS: A cyst of the iris or ciliary body causing a tumor of the iris was found in six cases (40%). Seven patients (47%) showed a solid tumor of the iris and two patients (13%) a solid tumor of the ciliary body. CONCLUSION: The ultrasound biomicroscope can be used to assess lesions of the iris caused by a cyst or a solid tumor. The increasing size and depth expansion of a solid tumor may be helpful for differentiating between a malignant or benign process. Up to now it has not been possible to use the ultrasonic reflectivity of the tumor to decide if it is malignant.

Adolescent↗