Search PubMed⌕ Search

Biomedical subjects

T Wagner

Publications and source records attributed to T Wagner.

At least 73 records · Page 4Linked to original sources
PubMed2001

A new h allele detected in Europe has a missense mutationin alpha(1,2)-fucosyltransferase motif II.

BACKGROUND: The FUT1 gene encodes an alpha(1,2)-fucosyltransferase (H transferase), which determines the blood group H. Nonfunctional alleles of this gene, called h alleles and carrying loss-of-function mutations, are observed in the exceedingly rare Bombay phenotype. Twenty-three distinct h alleles have been characterized at the molecular level in various populations. The FUT2 (SE) gene is highly homologous to FUT1 (H:). STUDY DESIGN AND METHODS: The FUT1 gene of an Austrian proband with the Bombay phenotype was characterized by nucleotide sequencing of the full-length coding sequence. A PCR method using sequence-specific primers for FUT2 genotyping in whites was developed. The plasma alpha(1,2)-fucosyltransferase activity was determined. The distribution of the mutations underlying 24 h alleles and 7 se alleles was analyzed. RESULTS: The proband carried a new h allele. Two nucleotide changes, G785A and C786A, in codon 262 of the FUT1 gene resulted in the replacement of serine by lysine. No alpha(1,2)-fucosyltransferase activity was detected in the proband's plasma. The proband was homozygous for the seG428A allele. Six of 17 missense mutations in nonfunctional h and se alleles occurred in highly conserved fucosyltransferase motifs. No loss-of-function mutation was observed in the aminoterminal section encompassing the transmembraneous helix. CONCLUSION: The missense mutation S262K in the FUT1 gene caused the loss of H transferase activity. The analysis of the distribution of mutations in nonfunctional FUT1 and FUT2 genes can point to functionally important domains in the H transferase.

ABO Blood-Group System↗
PubMed2001

IL-10 increases the number of CFU-GM generated by ex vivo expansion of unmanipulated human MNCs and selected CD34+ cells.

BACKGROUND: Ex vivo expansion strategies with different cytokine combinations are currently used by several groups as a means of increasing the number of HPCs for a variety of special clinical applications. Because there is little information on the potential role of IL-10 in such ex vivo expansion models, the effect of this cytokine on the generation of myeloid progenitor cells in suspension cultures was investigated. STUDY DESIGN AND METHODS: On the basis of data from the literature and from new experiments, the combination of SCF and IL-3 at concentrations of 100 ng per mL and 100 U per mL, respectively, was chosen as the standard cocktail. The addition of IL-10 to such cultures resulted in a marked and dose-dependent potentiation of myeloid progenitor cell production. RESULTS: Using unmanipulated leukapheresis components from 13 individuals (including lymphoma and cancer patients and normal donors), the expansion multiple of CFU-GM after 14 days as compared with pre-expansion values was 9.54 +/- 2.31 times by SCF/IL-3 and 46.38 +/- 7.37 times by the combination of SCF/IL-3 and 100 ng per mL of IL-10 (p<0.001). IL-10 also potentiated CFU-GM generation from selected CD34 PBMNCs (n = 9) with an expansion of 17.22 +/- 7.04 times versus 45.67 +/- 16.78 times using the SCF/IL-3 and SCF/IL-3/IL-10 combination, respectively (p<0.05). Moreover, expansion-promoting effects of IL-10 were observed in liquid cultures containing MNCs from bone marrow (n = 4) and cord blood (n = 3), but did not reach statistical significance because of the small number of samples. CONCLUSION: These results suggest IL-10 as a useful cytokine to optimize progenitor cell-expansion strategies for clinical application.

Antigens, CD34↗
PubMed2001

Lipoblastoma and lipoblastomatosis: a report of two cases and review of the literature.

Lipoblastoma and lipoblastomatosis are rare benign neoplasms of foetal white fat tissue that occur almost exclusively in infants and children. Two cases are reported and a review of the literature is given. An almost one-year-old girl and a full-term male infant were brought to our hospital with a solid mass in the right thigh. Nine months after total excision of the lipoblastoma, the little girl developed tumour recurrence, with unexpected histopathological maturation. In the case of the little boy, lipoblastomatosis with infiltration of the surrounding muscles, together with involvement of the sciatic and posterior femoral cutaneous nerves was found. Histologically, the tumour showed an unusual inflammatory reaction. The diagnosis of this tumour was made by the pathologist, but the histopathological picture bears a striking similarity to myxoid liposarcoma, and may be indistinguishable. Recent studies describe rearrangements of chromosome 8 q11-q13 region as a new discriminative marker that distinguishes lipoblastoma and lipoblastomatosis from myxoid liposarcoma.

Biopsy↗
PubMed2001

A semiautomatic method for adding behavioral data to videotape records in combination with the Noldus Observer system.

The Observer 3.0 (Noldus, 1991) was used as the base for a time-saving fine analysis of animal behavior. A PC controlled a shuttlebox and a shuttlebox control unit. Learning behavior was recorded on videotapes by an S-VHS camcorder with vertical interval time code (VITC), which was used to generate an observational data file (ODF). The observational system was enhanced by automatically recorded status signals from the PC as event markers on the soundtrack of the videotape. These signals were used to subdivide a training session into numbered trials during generation of the ODF. They were later used for a PC-aided fine analysis of behavioral events, such as attention responses (AR) and orienting responses (OR) during shuttlebox learning. In this way, a large number of both automatically inserted PC event markers and manually inserted, key-defined behavioral events were registered and analyzed effectively in a semiautomatic fashion. The system is illustrated with an analysis of shuttle-box avoidance data from gerbils (Meriones unguiculatus).

Acoustic Stimulation↗
PubMed2001

Radioisotope guided pelvic lymph node dissection for prostate cancer.

PURPOSE: The localization of lymph node metastases in prostate cancer varies enormously. Due to high morbidity complete pelvic lymphadenectomy is often decreased to modified staging lymphadenectomy, resulting in loss of sensitivity for detecting micrometastases. Based on the promising results of intraoperative gamma probe application for identifying sentinel lymph nodes in malignant melanoma, breast and penis cancer, we identified sentinel lymph nodes in prostate cancer using a comparable technique. MATERIALS AND METHODS: In 117 patients 99mtechnetium nanocolloid was transrectally injected directly into the prostate under ultrasound guidance 1 day before pelvic lymphadenectomy. Thereafter dynamic lymphoscintigraphy was done. Initially lymph nodes identified as sentinel lymph nodes by the gamma probe were removed and subsequently modified pelvic lymphadenectomy was performed. RESULTS: Lymphatic metastasis was detected in 28 cases. An average of 4 sentinel lymph nodes were identified per patient in 25 of 27 patients with micrometastasis, of which those in 24 contained micrometastasis for 96% sensitivity. In contrast, sensitivity of modified pelvic lymphadenectomy was 81.5%. In 16 patients only sentinel lymph nodes were positive. An average of 21.8 lymph nodes (range 10 to 51) was dissected per patient at pelvic lymphadenectomy. Lymph node metastasis was noted in 6 of the 46 patients with a prostate specific antigen between 4 and 10 ng./ml. and in 8 of the 64 with a stage pT2 tumor. CONCLUSIONS: Our study shows individual variability of lymphatic drainage of the prostate and limited sensitivity for detecting positive lymph nodes when the pelvic dissection area is limited. Furthermore, our experience implies that the identification of sentinel lymph nodes is feasible, not only in breast cancer and malignant melanoma, but also in prostate cancer using a comparable technique.

Aged↗
PubMed2001

The anatomy of the tendon of infundibulum.

The heart, as we know, is a muscular tissue supported by collagenous structures forming the fibrous skeleton of the heart. A structure by the name of the tendon of infundibulum appeared in the literature with no definite information about its structure or even its existence. The tendon of infundibulum was described as a strip of fibrous tissue structure situated between the aortic root and pulmonary trunk. Our study involved 30, formalin fixed, adult human hearts ranging from 18 to 81 years. Classical macroscopic anatomical methods were applied to observe macroscopically all the connections between the aorto-pulmonary trunk, together with serial transverse histological sections, through roots of the aorta and pulmonary trunk, using eosin-hematoxylin and van Gieson staining. All the hearts seemed to encompass many fascial bands attended by connective tissue. However these fascial bands are not concrete structures and cannot be termed tendons. In our investigation we have been unable to demonstrate macroscopically or histologically any structure which could be significantly approximating to the initial description of the literature. However, as far as we are able to judge, the term tendon of infundibulum has erroneously been introduced into many medical textbooks since the literature cannot still prove its existence.

Adolescent↗
PubMed2000

Stages of avoidance strategy formation in gerbils are correlated with dopaminergic transmission activity.

This detailed analysis of behavior is aimed at the differentiation of the components of information processing during associative conditioning. In gerbils, the influences of various acquired non-avoidance strategies as pre-experience were studied during the learning of a standard avoidance task in the same shuttle-box. Identical cue stimuli, frequency-modulated tones as conditioned stimuli and electric footshocks as unconditioned stimuli, were used in various behavioral tasks. In addition to common parameters such as avoidance performance and reaction times, behavioral events such as the attention response and the orienting response were quantified. Thereby, components of shuttle-box learning such as signal detection and signal evaluation were found to be affected by pre-experience-dependent dynamics. Using a microdialysis technique during avoidance learning in the shuttle-box, we found that only strategy formation was correlated with high dopamine levels in medial prefrontal cortex. The increase in dopamine in medial prefrontal cortex may be an indicator of the involvement of working memory principles in signal evaluation stages of conditioning.

Animals↗
PubMed2000

3-Deoxy-D-manno-octulosonate-8-phosphate synthase from Escherichia coli. Model of binding of phosphoenolpyruvate and D-arabinose-5-phosphate.

The crystal structure of 3-deoxy-d-manno-octulosonate-8-phosphate synthase (KDOPS) from Escherichia coli was determined by molecular replacement using coordinates given to us by Radaev and co-workers prior to publication. The KDOPS crystals reported by Radaev et al. were grown in the presence of 1.4 M (NH(4))(2)SO(4) and 0.4 M (K/H)(3)PO(4). They are in the cubic space group I23 (a=228.6 A) with a tetramer in the asymmetric unit; the structure has been refined with data to 2.4 A. Our crystals of E. coli KDOPS, grown in 24 % (w/v) polyethylene glycol (PEG) 1500 in the presence of the substrates, 2-phosphoenolpyruvate (PEP) and d-arabinose-5-phosphate (A5P), are also in space group I23 (a=118.2 A), with one subunit in the asymmetric unit. The medium of crystallization, 1.8 M SO(4)/PO(4) versus 24 % PEG, does not significantly affect the conformation of KDOPS. The inter-monomer contacts in both structures are the same. The beta(8)/alpha(8) loop (residues 246 to 251) situated near the entrance to the active site is not seen in the 229 A structure but can be traced in the 118 A structure. Most significantly, Radaev et al. interpreted two SO(4)/PO(4) sites in the 229 A structure as marking the phosphate positions of the substrates, PEP and A5P, after the precedent of DAHPS. In the 118 A structure the inner of these two SO(4)/PO(4) peaks is present at the same position as in the 229 A structure of KDOPS. The outer phosphate peak in the 118 A KDOPS is 3.7 A from the outer SO(4)/PO(4) peak in the 229 A structure and is within hydrogen bonding distance of Arg63 of the same subunit and Arg120 of another subunit. Based on the precedent of the d-erythrose-4-phosphate (E4P) modeled in the active site of DAHPS, we have modeled PEP and A5P in KDOPS and compared the coordination of PEP and A5P in KDOPS with that of PEP and E4P in DAHPS.

Aldehyde-Lyases↗
PubMed2000

Structure of 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase from Escherichia coli: comparison of the Mn(2+)*2-phosphoglycolate and the Pb(2+)*2-phosphoenolpyruvate complexes and implications for catalysis.

The crystal structure of the phenylalanine-regulated 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (DAHPS) from Escherichia coli in complex with Mn(2+) and the substrate analog, 2-phosphoglycolate (PGL), was determined by molecular replacement using X-ray diffraction data to 2.0 A resolution. DAHPS*Mn*PGL crystallizes in space group C2 (a=210.4 A, b=53.2 A, c=149.4 A, beta=116.1 degrees ) with its four (beta/alpha)(8) barrel subunits related by non-crystallographic 222 symmetry. The refinement was carried out without non-crystallographic symmetry restraints and yielded agreement factors of R=20.9 % and R(free)=23.9 %. Mn(2+), the most efficient metal activator, is coordinated by the same four side-chains (Cys61, His268, Glu302 and Asp326) as is the poorly activating Pb(2+). A fifth ligand is a well-defined water molecule, which is within hydrogen bonding distance to an essential lysine residue (Lys97). The distorted octahedral coordination sphere of the metal is completed by PGL, which replaces the substrate, 2-phosphoenolpyruvate (PEP), in the active site. However, unlike PEP in the Pb*PEP complex, PGL binds the Mn(2+) via one of its carboxylate oxygen atoms. A model of the active site is discussed in which PEP binds in the same orientation as does PGL in the DAHPS*Mn*PGL structure and the phosphate of E4P is tethered at the site of a bound sulfate anion. The re face of E4P can be positioned to interact with the si face of PEP with only small movement of the protein.

3-Deoxy-7-Phosphoheptulonate Synthase↗
PubMed2000

The inhibitory influence of an acquired escape strategy on subsequent avoidance learning in gerbils.

In gerbils an acquired non-avoidance strategy as pre-experience in a shuttle-box was studied in its influence on the learning of a standard avoidance paradigm. Thereby the same cue stimuli, frequency modulated tones (CS) and electric footshocks (US) were used in different behavioral paradigms. In the preexperience sessions the interstimulus interval between CS and US and on the other hand the escapability or inescapability of the US was varied. It was found that the experience with a relatively long interstimulus interval led to a prolonged maintenance of an acquired escape strategy during subsequent standard avoidance learning. This effect increased with the preexperience of an inescapable US. Additional insights into the temporal inhibition of avoidance learning by the pre-experience were provided by behavioral events like attention responses and orienting responses reflecting components of information processing.

Acoustic Stimulation↗
PubMed2000

Structure of the RXR-RAR DNA-binding complex on the retinoic acid response element DR1.

The 9-cis retinoic acid receptor (retinoid X receptor, RXR) forms heterodimers with the all-trans retinoic acid receptor (RAR) and other nuclear receptors on DNA regulatory sites composed of tandem binding elements. We describe the 1.70 A resolution structure of the ternary complex of RXR and RAR DNA-binding regions in complex with the retinoic acid response element DR1. The receptors recognize identical half-sites through extensive base-specific contacts; however, RXR binds exclusively to the 3' site to form an asymmetric complex with the reverse polarity of other RXR heterodimers. The subunits associate in a strictly DNA-dependent manner using the T-box of RXR and the Zn-II region of RAR, both of which are reshaped in forming the complex. The protein-DNA contacts, the dimerization interface and the DNA curvature in the RXR-RAR complex are distinct from those of the RXR homodimer, which also binds DR1. Together, these structures illustrate how the nuclear receptor superfamily exploits conformational flexibility and locally induced structures to generate combinatorial transcription factors.

Amino Acid Sequence↗
PubMed2000

Mutational analyses of BRCA1 and BRCA2 in Ashkenazi and non-Ashkenazi Jewish women with familial breast and ovarian cancer.

In Ashkenazi (East European) Jews, three predominant mutations in BRCA1 (185delAG and 5382insC) and BRCA2 (6174delT) account for the majority of germline mutations in high-risk breast and/or ovarian cancer families. Among non-Ashkenazi Jews, the 185delAG, Tyr978Ter, and a handful of "private" mutations have been reported anecdotally within both genes. In this study we attempted to determine the spectrum of BRCA1 and BRCA2 mutations in high-risk Jewish individuals, non-carriers of any of the predominant Jewish mutations. We employed multiplex PCR and denaturing gradient gel electrophoresis (DGGE) analysis for BRCA2, and combined denaturing high performance liquid chromatography (DHPLC) and protein truncation test (PTT) for BRCA1, complemented by DNA sequencing. We screened 47 high-risk Jewish individuals, 26 Ashkenazis, and 21 non-Ashkenazis. Overall, 13 sequence alterations in BRCA1 and eight in BRCA2 were detected: nine neutral polymorphisms and 12 missense mutations, including five novel ones. The novel missense mutations did not co-segregate with disease in BRCA1 and were detected at rates of 6.25% to 52.5% in the general population for BRCA2. Our findings suggest that except for the predominant mutations in BRCA1 and BRCA2 in Jewish individuals, there are only a handful of pathogenic mutations within these genes. It may imply novel genes may underlie inherited susceptibility to breast/ovarian cancer in Jewish individuals.

Adult↗
PubMed2000

The density of apical cells of dark-grown protonemata of the moss Ceratodon purpureus.

Determinations of plant or algal cell density (cell mass divided by volume) have rarely accounted for the extracellular matrix or shrinkage during isolation. Three techniques were used to indirectly estimate the density of intact apical cells from protonemata of the moss Ceratodon purpureus. First, the volume fraction of each cell component was determined by stereology, and published values for component density were used to extrapolate to the entire cell. Second, protonemal tips were immersed in bovine serum albumin solutions of different densities, and then the equilibrium density was corrected for the mass of the cell wall. Third, apical cell protoplasts were centrifuged in low-osmolarity gradients, and values were corrected for shrinkage during protoplast isolation. Values from centrifugation (1.004 to 1.015 g/cm3) were considerably lower than from other methods (1.046 to 1.085 g/cm3). This work appears to provide the first corrected estimates of the density of any plant cell. It also documents a method for the isolation of protoplasts specifically from apical cells of protonemal filaments.

Bryopsida↗
PubMed2000

[Pigmented villonodular synovitis. A rare differential diagnosis of popliteal space-occupying lesion].

Pigmented villonodular synovitis (PVNS) is a disease that involves the lining of joints, bursae and tendon sheaths. The incidence is low and estimated to be 1.8 patients per million population. The cause of PVNS is unclear and discussed to be either inflammatory or neoplastic. PVNS has been described in 2 forms different for prognosis and treatment (nodular and diffuse). The articular form almost appears in the knee joint as we describe below in a 14 year-old patient. PVNS was first defined in 1941 by Jaffe e.a. [7]. Because of the uncommon occurrence of the disease it is difficult to amass patient series to allow confirmed statements on therapy and outcome. Larger patient series raise out of long periods of time. Differences in outcome and recurrence rates exist for the nodular and diffuse form. Clinical findings are moderate pain and swelling of joints due to effusion and synovial proliferation. Magnetic resonance imaging shows typical findings. Surgical procedures are recommended as open or arthroscopic synovectomy for the diffuse form of PVNS, local excision for the nodular form and arthrodesis or prosthetic replacement for joint destruction.

Adolescent↗
PubMed2000

The superior olivary complex is necessary for the full expression of the acoustic but not tactile startle response in rats.

The acoustic startle response (ASR) in rats is mediated by an oligosynaptic pathway from the cochlea via the brainstem to spinal and cranial motoneurons. The present study tested whether the superior olivary complex (SOC) plays a role in the mediation of the ASR. The SOC receives auditory information from the ventral cochlear nuclei and projects to the caudal pontine reticular nucleus (PnC), the sensorimotor interface of the ASR. Axon-sparing excitotoxic lesions of the SOC strongly reduced the ASR amplitude and slightly prolonged ASR onset and peak latencies. The integrity of PnC which is adjacent to the SOC was confirmed by testing the tactile startle response which was not affected by SOC lesions. We suggest that the SOC is necessary for a full expression of the ASR and discuss possible auditory input structures involved in the mediation of the ASR.

Acoustic Stimulation↗
PubMed2000

1,25-Dihydroxyvitamin D(3) inhibits dendritic cell differentiation and maturation in vitro.

OBJECTIVE: Because of its potent immunosuppressive properties in vitro as well as in vivo, we studied the effect of 1,25-dihydroxyvitamin D(3) (calcitriol) on differentiation, maturation, and function of dendritic cells (DC). MATERIALS AND METHODS: Monocyte-derived DCs were generated with GM-CSF plus IL-4, and maturation was induced by a 2-day exposure to TNFalpha. DCs were derived from CD34(+) progenitors using SCF plus GM-CSF plus TNFalpha. For differentiation studies, cells were exposed to calcitriol at concentrations of 10(-)(9)- 10(-7) M at days 0, 6, and 8, respectively. The obtained cell populations were evaluated by morphology, phenotype, and function. RESULTS: When added at day 0, calcitriol blocked DC differentiation from monocytes and inhibited the generation of CD1a(+) cells from progenitor cells while increasing CD14(+) cells. Exposure of immature DCs to calcitriol at day 6 resulted in a loss of the DC-characteristic surface molecule CD1a, downregulation of the costimulatory molecules CD40 and CD80, and MHC class II expression, whereas the monocyte/macrophage marker CD14 was clearly reinduced. In addition, calcitriol hindered TNFalpha-induced DC maturation, which is usually accompanied with induction of CD83 expression and upregulation of costimulatory molecules. In contrast, the mature CD83(+) DCs remained CD1a(+)CD14(-) when exposed to calcitriol. The capacity of cytokine-treated cells to stimulate allogeneic and autologous T cells and to take up soluble antigen was inhibited by calcitriol. CONCLUSION: The potent suppression of DC differentiation, the reversal of DC phenotype, and function in immature DCs, as well as the inhibition of DC maturation by calcitriol, may explain some of its immunosuppressive properties.

Antigens, CD↗