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Biomedical subjects

T Wagner

Publications and source records attributed to T Wagner.

At least 163 records · Page 9Linked to original sources
PubMed1995

Microvessel density and vessel invasion in lymph-node-negative breast cancer: effect on recurrence-free survival.

Microvessel density (MVD) and blood and lymphatic vessel invasion (BLVI) were investigated with regard to their influence on the disease-free survival (DFS) in node-negative breast cancer patients. Paraffin embedded microsections of 230 patients with T1,2 N0 breast cancer were immunohistochemically stained for factor VIII-related antigen. Every cluster consisting of more than highlighted endothelial cells was considered a countable microvessel. MVD was counted in 4 fields of 0.25 mm2 each. All MVD values are given as value for the sum of 4 fields of 0.25 mm2 each, that is, I mm2. BLVI was considered positive, when at least one tumor cell could be identified in a stained lumen. Out of 230 patients, 49 experienced local or distant recurrence and had a mean MVD of 72.4/mm2, whereas 181 patients who lived without recurrent disease had a mean MVD of 45.3/mm2. BLVI was negative in 6.2% of the cases with and in 93.8% of the cases without recurrent disease. BLVI was positive in 59.4% of the cases without and 40.6% of the cases with recurrent disease. MVD and BLVI remained the only significant prognostic factors of DFS in the Cox-Model. Tumor size, histological grade, and hormonal-receptor status were not prognostically relevant in the Cox-model. 10-year-DFS was 93.3% in BLVI-negative/MVD < or = 40/mm2 patients, 88.1% when MVD was high or BLVI was positive and 48.9% in BLVI positive/MVD < or = 40/mm2 patients. Our present data indicate that MVD and BLVI identify a very-low risk group among node-negative breast cancer patients, who will not benefit from systemic adjuvant therapy. MVD and BLVI should be used as stratification criteria in clinical trails on node-negative breast cancer patients.

Adult↗
PubMed1995

The human plakoglobin gene localizes on chromosome 17q21 and is subjected to loss of heterozygosity in breast and ovarian cancers.

The gene encoding human plakoglobin was mapped to chromosome 17q12-q22. An intragenic restriction fragment length polymorphism was used to localize the plakoglobin gene distal to locus KRT10 and proximal to the marker D17S858. The plakoglobin gene colocalizes with the polymorphic 17q21 marker UM8 on the same cosmid insert. This subregion of chromosome 17 is known to be particularly subjected to genetic alterations in sporadic breast and ovarian tumors. We show loss of heterozygosity of the plakoglobin gene in breast and ovarian tumors. We have identified a low-frequency polymorphism in the plakoglobin coding sequence which results in an arginine to histidine substitution at amino acid position 142 of the protein, as well as a silent mutation at nucleotide position 332 of the coding sequence. This polymorphism allowed us to demonstrate an allelic association of plakoglobin with predisposition to familial breast and ovarian cancers. Our results, together with the present knowledge about the biological function of plakoglobin, suggest that plakoglobin might represent a putative tumor suppressor gene for breast and ovarian cancers.

Amino Acid Sequence↗
PubMed1995

Differential regulation of G protein alpha-subunit GTPase activity by peptides derived from the third cytoplasmic loop of the alpha 2-adrenergic receptor.

The effect of peptides homologous to segments of a G protein-coupled receptor on the GTPase activity of recombinant Go alpha (rGo alpha) and Gs alpha (rGs alpha) has been tested. These peptides contain overlapping sequences spanning from amino acid 212 of the putative fifth transmembrane domain to amino acid 229 of the third cytoplasmic loop of the alpha 2 adrenergic receptor. Interestingly, two peptides (comprising residues 212-227 and 214-227) strongly inhibit the basal GTPase activity of both rGo alpha and rGs alpha. Instead, a C-terminally extended peptide (residues 216-229) stimulates rGo alpha but slightly inhibits rGs alpha. Circular dichroism spectroscopy of the peptides reveals that an a helical structure is more easily inducible in the inhibitory ones. These findings constitute an example of peptides representing cytoplasmic receptor sequences that differentially modulate the GTPase activity of recombinant G protein alpha-subunits.

Amino Acid Sequence↗
PubMed1995

Targeted overexpression of luteinizing hormone in transgenic mice leads to infertility, polycystic ovaries, and ovarian tumors.

Hypersecretion of luteinizing hormone (LH) is implicated in infertility and miscarriages in women. A lack of animal models has limited progress in determining the mechanisms of LH toxicity. We have recently generated transgenic mice expressing a chimeric LH beta subunit (LH beta) in gonadotropes. The LH beta chimera contains the C-terminal peptide of the human chorionic gonadotropin beta subunit. Addition of this peptide to bovine LH beta resulted in a hormone with a longer half-life. Furthermore, targeted expression of the LH beta chimera led to elevated LH levels and infertility in female transgenics. These mice ovulated infrequently, maintained a prolonged luteal phase, and developed pathologic ovarian changes such as cyst formation, marked enlargement of ovaries, and granulosa cell tumors. Testosterone and estradiol levels were increased compared to nontransgenic littermates. An unusual extragonadal phenotype was also observed: transgenic females developed hydronephropathy and pyelonephritis. The pathology observed demonstrates a direct association between abnormal secretion of LH and infertility and underscores the utility of the transgenic model for studying how excess LH leads to cyst formation, ovarian tumorigenesis, and infertility.

Animals↗
PubMed1995

Specific tropism caused by ultraviolet C radiation in Phycomyces.

The giant sporangiophores of Phycomyces blakesleeanus turn towards blue and away from ultraviolet C sources (wavelength under 310 nm). We have isolated fifteen mutants with normal blue tropism but defective ultraviolet tropism. Wild-type sporangiophores described a double turn when exposed successively to blue and ultraviolet beams coming from the same side; under certain conditions, the mutants turned only to the blue. The new uvi mutations modified the behaviour in heterokaryosis and were lethal in homokaryosis, i.e., they affected essential cellular components. The responses of the wild type and one of the mutants were registered and evaluated with a computer-aided device. The mutant behaved normally under blue light, but took longer than the wild type to turn away from the ultraviolet source. With very weak ultraviolet stimuli (10(-8) and l0(-9) W m-2), the wild type turned towards the source, but the mutant did not respond. Calculations of absorbed-energy distributions in the sporangiophore showed that Phycomyces responds differently to similar spatial distributions of blue and ultraviolet radiations. Wild-type and mutant sporangiophores had the same high ultraviolet absorption due to gallic acid. We conclude that ultraviolet tropism is not just a modification of blue phototropism due to the high ultraviolet absorption of the sporangiophores. Phycomyces has a separate sensory system responsive to ultraviolet radiation, but not to blue light.

Gallic Acid↗
PubMed1995

The morphology of xenotransplanted human breast carcinoma MX-1 growing in nude mice. A light and transmission electron microscopic study.

The present investigation is concerned with the morphological features of the human breast carcinoma MX-1, transplanted subcutaneously into nude mice. Three weeks after transplantation the tumor tissue is clearly distinct from the dermis. Solid tumor cell groups are separated incompletely by thin connective tissue septa, giving rise to a lobular appearance. The tumor cells are characterized by very irregularly formed nuclei with three or more nucleoli. The cytoplasm of these cells displays some lysosomes, the cisternae of the rough endoplasmic reticulum, mitochondria and a variable number of ribosomes. The Golgi fields are frequently observed, particularly near the nucleus. The cells are connected to each other by desmosomes, which also persist during mitotic activity. Ductular formations can occasionally be seen. The ultrastructure of the blood vessels discloses the morphological features necessary for the regulation of blood flow. Capillaries present a sinusoidal aspect with distended and narrow lumina. Interruptions of the endothelial wall, however, were not observed. This morphological appearance was found in all the MX-1 tumors investigated, reflecting the stable growth of this tumor cell line in nude mice.

Animals↗
PubMed1995

Expression of rabbit C-reactive protein in transgenic mice.

C-reactive protein (CRP) is a prototypic acute phase reactant in humans and rabbits whose serum concentration can increase up to 1000-fold following an acute inflammatory stimulus. CRP binds to many phosphate ester-containing compounds including phosphorylcholine, nucleotides, chromatin and snRNP. To examine the in vivo function of this protein, we produced transgenic mice capable of significant CRP synthesis. In contrast to most other vertebrates, mice synthesize CRP in only trace amounts. The transgenic animals express rabbit CRP from either the phosphoenolpyruvate carboxykinase promoter (PEPCK-CRP) or the mouse metallothionein I promoter (MT-CRP). Manipulating the diet in one of the PEPCK-CRP lines led to a rise in serum CRP levels from < 5 mu g/mL to 100-200 mu g/mL over a period of 2 days. The two MT-CRP lines examined expressed CRP constitutively which could be further elevated 2-4-fold following an inflammatory stimulus. Transgenic CRP bound phosphorylcholine was pentameric, had a circulating half-life of 30-60 min and was capable of activating mouse complement when bound to a ligand. We conclude that these transgenic lines express CRP with many of the properties of authentic rabbit CRP, and that the expression of CRP can be controlled to be dependent or independent of the acute phase response.

Acute-Phase Reaction↗
PubMed1995

Intermittent regional therapy with rt-PA is not superior to systemic thrombolysis in deep vein thrombosis (DVT)--a German multicenter trial.

In a prospective and randomized multicenter trial the efficacy of intermittent regional and systemic thrombolytic therapy for DVT was evaluated. 137 patients with phlebographically confirmed acute DVT above the calf region were treated with 20 mg of rt-PA for 4 h each day. Thrombolysis was applied either locally via a dorsal pedal vein of the firmly bandaged affected leg or systemically using a cubital vein. Treatment lasted for 4-7 days, and during this time unfractionated heparin was applied continuously with the dosage adjusted according to aPTT (1.5-2.0 times the normal value). A second phlebography was performed within 24 h after the end of treatment. Results were evaluated by an independent radiologist who was unaware of the treatment given. Significant thrombolytic results (e.g. lysis of more than 50% of the original thrombus and complete recanalization of all affected veins) were reached in only 1/3 of all patients. Rates of recanalization did not differ in both groups and bleeding complications occurred in 26.5%. We conclude that intermittent local or systemic application of 20 mg rt-PA seems to be ineffective in the treatment of DVT.

Adolescent↗
PubMed1994

Intrinsic properties of identified neurones in the central nucleus of mouse inferior colliculus.

The intrinsic properties of morphologically identified neurones in the central nucleus of the inferior colliculus (ICC) were investigated using a mouse brain slice preparation. Thirty-four neurones were physiologically characterized and classified into three response types: onset, intermediate and sustained. Thirteen were stained intracellularly and appeared to be multipolar cells spanning several fibrodendritic laminae of the ICC with their dendritic trees. Onset-type neurones showed only a small afterhyperpolarization and often a rectification to depolarizing current pulses. Thus, the suggestion is put forward that onset-type cells are especially well suited for coincidence detection of incoming auditory stimuli over a broad range of frequencies, whereas sustained-type neurones may perform different tasks in integrating and regulating the auditory input to the ICC.

Animals↗
PubMed1994

Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9.

A human autosomal XY sex reversal locus, SRA1, associated with the skeletal malformation syndrome campomelic dysplasia (CMPD1), has been placed at distal 17q. The SOX9 gene, a positional candidate from the chromosomal location and expression pattern reported for mouse Sox9, was isolated and characterized. SOX9 encodes a putative transcription factor structurally related to the testis-determining factor SRY and is expressed in many adult tissues, and in fetal testis and skeletal tissue. Inactivating mutations on one SOX9 allele identified in nontranslocation CMPD1-SRA1 cases point to haploinsufficiency for SOX9 as the cause for both campomelic dysplasia and autosomal XY sex reversal. The 17q breakpoints in three CMPD1 translocation cases map 50 kb or more from SOX9.

Amino Acid Sequence↗
PubMed1994

DXS106 and DXS559 flank the X-linked dystonia-parkinsonism syndrome locus (DYT3).

The locus (DYT3) underlying the X-linked dystonia-parkinsonism syndrome (XDP) was delineated within proximal Xq12-Xq13.1 by analysis of linkage, allelic association, and haplotypes. Short tandem repeat polymorphisms at loci DXS227, DXS559, DXS453, DXS106, DXS339, and DXS135 were studied. The occurrence of a recombination within a three-generation family established DXS559 as the distal flanking marker of DYT3. /phi/ and /delta/ values were determined as indicators of the degree of allelic association between DYT3 and the six marker loci. In addition, haplotype analysis was performed at the loci studied. The findings establish DXS106 as the proximal flanking marker of DYT3. Given an approximate distance between DXS106 and DXS559 of 3.0 Mb, isolation of DYT3 is now feasible by positional cloning techniques.

Alleles↗
PubMed1994

Intraosseous leiomyoma of the neck of the femur. A case report.

Intraosseous benign leiomyoma is a rare manifestation of disseminated leiomyomatosis. In a 54 year old housewife presenting with a painful left hip due to a cystic lesion of the femoral neck, histological assessment following resection of the cyst showed a benign intraosseous leiomyoma. Years before a diagnosis of disseminated peritoneal leiomyomatosis had been made.

Biopsy↗
PubMed1994

Effects of CLIP (corticotropin-like intermediate lobe peptide) and CLIP fragments on paradoxical sleep in rats.

The effects of the POMC-derived peptide CLIP [corticotropin-like intermediate lobe peptide; ACTH(18-39)] and its shorter fragments ACTH(25-39), ACTH(18-24), and ACTH(20-24) on sleep were investigated in rats housed under normal 12-h light/12-h dark conditions (0600 light on). CLIP (10 ng) or equimolar doses of CLIP fragments, respectively, were injected intracerebroventricularly immediately before the 8-h recording period (0800-1600). It was found that paradoxical sleep (PS) was increased by CLIP (+20%) as well as by the N-terminal CLIP fragment ACTH(18-24) (+18%) and by the pentapeptide ACTH(20-24) (+25%), whereas the C-terminal fragment ACTH(25-39) was ineffective. Slow-wave sleep (SWS) was not influenced. These results clearly demonstrate that CLIP and its N-terminal fragments have selective PS-enhancing effects. CLIP and/or CLIP partial sequences are possible candidates for endogenous PS-inducing peptides involved in the physiological regulation of paradoxical sleep.

Adrenocorticotropic Hormone↗
PubMed1994

Does cord blood contain enough progenitor cells for transplantation?

We analyzed 125 blood samples obtained from umbilical cord immediately after delivery of full-term neonates. Between 0.1 and 10.4% (mean 1.13%, SD 1.34) of the density-separated glycophorin A (GPA)-negative mononuclear cells (MNC) expressed CD34 as analyzed by flow cytometry. These hematopoietic progenitor cells did not coexpress CD19, and the majority were negative for CD45RA. The number of MNC determined per ml cord blood ranged from 1 x 10(5) to 200 x 10(5) (mean 20.2 x 10(5), SD 24.7). Regression analysis revealed that a mean of 56% (n = 26, R = 0.8) and 120% (n = 35, R = 0.94) of the analyzed CD34+ MNC gave rise to day 14 colonies in the clonogenic assay when cultured without or with stem cell factor (SCF). The number and the exact phenotype of progenitor cells required for successful transplantation are not known. If the transplantation of 5 x 10(5) CD34% cells/kg body weight is required for engraftment and one-third of the progenitor cells are lost to cell processing, and if 180 ml blood can be collected from a single umbilical cord (and placenta), our data suggest that 90% of the collections do not contain enough precursors to transplant a 25 kg recipient. To meet these conditions, an average of 1439 ml cord blood would be necessary for transplantation.

Colony-Forming Units Assay↗