Biomedical subjects

W Muller

Publications and source records attributed to W Muller.

At least 19 recordsLinked to original sources

PubMed2001

FM1-43 imaging reveals cGMP-dependent long-term depression of presynaptic transmitter release.

A persistent question concerning mechanisms underlying long-term, activity-dependent synaptic plasticity is whether the sites of alterations are presynaptic, postsynaptic, or both. Recently, we discovered a chemical method of inducing long-term depression (LTD) of synaptic strength at Schaffer collateral-CA1 synapses by simultaneously elevating [cGMP] and inhibiting cAMP-dependent protein kinase (PKA). Chemical LTD (CLTD) is activity-independent, occluded by stimulus-evoked LTD, and requires access of pharmacologic agents to presynaptic terminals. In the present study, we used fluorescence and two-photon imaging of presynaptic terminals with the fluorescent dye N-(3-triethylammoniumpropyl)-4-(4-(dibutylamino)styryl) pyridinium dibromide (FM1-43) to determine directly if inducing CLTD is associated with a long-term reduction in transmitter release. In presynaptic Schaffer collateral-CA1 terminals of control hippocampal slices loaded with FM1-43, electrical stimulation (10 Hz/2 min) elicited a frequency-dependent destaining that peaked at 20% reduction in fluorescence. In contrast, when we first induced CLTD by a 30 min treatment of slices with the type V phosphodiesterase inhibitor zaprinast (20 microm) plus the PKA inhibitor N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89; 10 microm), then washed for 60 min, the destaining of FM1-43 fluorescence evoked by the same stimulation was reduced to 4%. Treatment and washout of slices with either drug singly had a significantly smaller effect on stimulus-evoked FM1-43 destaining. Only CLTD was associated with virtually complete suppression of stimulus-evoked FM1-43 release, the first direct evidence for at least one form of LTD being mediated by persistent reduction of presynaptic transmitter release.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2001

Fracture treatment in children--data analysis and follow-up results of a prospective study.

The versatile Orthofix modular system can be used to treat long-bone fractures in children from the 2nd year of life. It allows definitive fracture management over a short period of time without traumatizing the soft tissues. The possible early mobilization and full weight-bearing mean that the children are able to return early to school or kindergarten. The method enables the stabilization of open fractures with or without excessive soft tissue injury as well as secondary callus distraction. There is no need for a second surgical intervention and no prolonged period of physiotherapy. This fracture treatment suits children's needs and maintains their quality of life.

Adolescent↗

PubMed2001

Induction of ErbB-2/neu-specific protective and therapeutic antitumor immunity using genetically modified dendritic cells: enhanced efficacy by cotransduction of gene encoding IL-12.

Overexpression of ErbB-2/neu occurs in 20-30% of patients with breast cancer and indicates a poor prognosis. The presence of a detectable immune response to ErbB-2/neu in some patients suggests that this oncogene may be a useful target for vaccine therapy. We evaluated whether genetic immunization using dendritic cells (DC) transduced ex vivo with an adenovirus expressing the ErbB-2/neu gene (AdNeuTK) could induce protective and therapeutic immunity against a breast tumor cell line overexpressing ErbB-2/neu. Subcutaneous (s.c.) immunization with the DC vaccine elicited protective immunity in an average of 60% of animals. CTL analysis demonstrated specific cytotoxic activity against breast tumor cells, as well as syngeneic fibroblasts transduced with AdNeuTK. In vivo depletion studies demonstrated both CD4+ and CD8+ T cells were required. In a therapeutic setting, immunization with the DC vaccines could cure mice with pre-established tumors and efficacy was further enhanced by cotransducing DCs with a vector expressing murine IL-12 (AdmIL-12). These studies support DC vaccines as a therapeutic strategy for human breast cancer, while emphasizing the importance of optimizing an immune response by combining tumor antigen presentation with immunostimulatory cytokines.

Adenoviridae↗

PubMed2000

Cloning of the murine thymic stromal lymphopoietin (TSLP) receptor: Formation of a functional heteromeric complex requires interleukin 7 receptor.

The cellular receptor for murine thymic stromal lymphopoietin (TSLP) was detected in a variety of murine, but not human myelomonocytic cell lines by radioligand binding. cDNA clones encoding the receptor were isolated from a murine T helper cell cDNA library. TSLP receptor (TSLPR) is a member of the hematopoietin receptor family. Transfection of TSLPR cDNA resulted in only low affinity binding. Cotransfection of the interleukin 7 (IL-7)Ralpha chain cDNA resulted in conversion to high affinity binding. TSLP did not activate cells from IL-7Ralpha(-/)- mice, but did activate cells from gammac(-/)- mice. Thus, the functional TSLPR requires the IL-7Ralpha chain, but not the gammac chain for signaling.

Amino Acid Sequence↗

PubMed2000

Isotopic dating of strain fringe increments: duration and rates of deformation in shear zones

The time scales over which deformation in the Earth's crust remains localized in shear zones are poorly known, as are the associated strain rates. We have determined the longevity and rates of deformation using rubidium-strontium (Rb-Sr) microsampling dating of increments of fibrous strain fringes from a Pyrenean shear zone. The fibers grew quasi-continuously through a protracted deformation history between 87 and 50 million years ago, over a period comparable to that of an orogeny. During a short interval between 66 and 62 million years, a rise in strain rate from 1.1 x 10(-15) to 7. 7 x 10(-15) seconds(-1) occurred. This acceleration correlates with an abrupt change in fiber-growth direction and a stress-field inversion from gravitational collapse to renewed horizontal crustal shortening.

Journal Article↗

PubMed2000

TNF-alpha gene polymorphism does not affect the clinical and radiological outcome of rheumatoid arthritis.

The present study was undertaken in order to investigate the relationship between tumor necrosis factor-alpha (TNF-alpha) gene polymorphism and the radiological progression of rheumatoid arthritis (RA) within the first 3-years of the disease. Sixty-eight RA patients (59 women and nine men) were observed for 3-years. TNF-alpha polymorphism analysis was performed in all patients. Radiographs of the hands were taken at the onset of study and after 3-years of follow-up. Radiographs were assessed according to the Larsen index (damage score and progression of damage score). We did not observe any correlation between TNF gene polymorphism and damage score or progression of damage score. The obtained data suggests that TNF-308 polymorphism cannot serve as an indicator of the disease course in RA patients.

Adult↗

PubMed2000

Experiences with synthetic aperture focusing technique in the field

The detection and evaluation of defects in industrial components relies strongly on ultrasonic inspection techniques. Distance gain size (DG) or reference reflector methods can be improved concerning their localization, signal-to-noise ratio and sizing accuracy by the synthetic aperture focusing technique (SAFT). To obtain a high quality image, parameters like focal probe versus contact technique probe, achieved resolution or features of SAFT images compared with B-scan images are discussed. The implementation of SAFT in a CAD environment allows us to present stacked 2D reconstructions dynamically. On a cladded testblock with half-penny shaped cracks the advantage of combining CAD with SAFT is shown. A 3D SAFT example finalizes the overview of two decades of experience in applying this technique.

Journal Article↗

PubMed2000

Reply

Explore the source record for details and available documents.

Journal Article↗

PubMed1999

The role of beta7 integrins in CD8 T cell trafficking during an antiviral immune response.

The requirement of beta7 integrins for lymphocyte migration was examined during an ongoing immune response in vivo. Transgenic mice (OT-I) expressing an ovalbumin-specific major histocompatibility complex class I-restricted T cell receptor for antigen were rendered deficient in expression of all beta7 integrins or only the alphaEbeta7 integrin. To quantitate the relative use of beta7 integrins in migration in vivo, equal numbers of OT-I and OT-I-beta7(-/-) or OT-I-alphaE-/- lymph node (LN) cells were adoptively transferred to normal mice. Although OT-I-beta7(-/-) LN cells migrated to mesenteric LN and peripheral LN as well as wild-type cells, beta7 integrins were required for naive CD8 T cell and B cell migration to Peyer's patch. After infection with a recombinant virus (vesicular stomatitis virus) encoding ovalbumin, beta7 integrins became critical for migration of activated CD8 T cells to the mesenteric LN and Peyer's patch. Naive CD8 T cells did not enter the lamina propria or the intestinal epithelium, and the majority of migration of activated CD8 T cells to the small and large intestinal mucosa, including the epithelium, was beta7 integrin-mediated. The alphaEbeta7 integrin appeared to play no role in migration during a primary CD8 T cell immune response in vivo. Furthermore, despite dramatic upregulation of alphaEbeta7 by CD8 T cells after entry into the epithelium, long-term retention of intestinal intraepithelial lymphocytes was also alphaEbeta7 independent.

Animals↗

PubMed1999

Molecular cloning of the Notophthalmus viridescens radical fringe cDNA and characterization of its expression during forelimb development and adult forelimb regeneration.

Larval and adult newts provide important experimental models to study limb development and regeneration. These animals have exceptional ability to regenerate their appendages, as well as other vital structures. Our research examines the role of the fringe gene (fng) in the developing and regenerating adult newt forelimb. Fringe codes for a secretory protein. It was first discovered in Drosophila, and later homologues were isolated in Xenopus laevis, chick and mouse. This gene has been highly conserved throughout evolution, indicating its crucial role in vertebrate and invertebrate development. We have isolated, cloned, and sequenced the full length of the Notophthalmus viridescens radical fringe cDNA (nrFng) by screening a newt forelimb blastema cDNA library with a 500-bp fragment of the Xenopus lunatic fringe cDNA. The newt fringe cDNA codes for a 396 amino acid protein with a predicted N-terminal signal sequence. Newt fringe shows high homology with radical fringe homologues of many species. Whole mount mRNA in situ hybridization on several stages of newt limb development reveals that nrFng is first expressed in the limb field, with intense expression as the limb bud develops. However, gene expression diminishes with more advanced digit development. A significant role in adult forelimb regeneration is also evident, as we isolated the cDNA from a regeneration-specific library and found it highly expressed during the regenerative phases of active cell division and then down regulated at sites undergoing differentiation and morphogenesis.

Amino Acid Sequence↗

PubMed1999

Models of local behavior of DNA electrophoresis peak parameters.

Many base calling algorithms implicitly or explicitly rely on predictions of local sequence parameters such as amplitude, peak time and peak width. For example, an algorithm may search for the next peak about a predicted peak time formed by adding the mean peak separation to the last position measurement. In this paper, covariance models are presented which characterize the dependence of peak parameters on those of other peaks. Based on experimental measurements, the model features an exponential decay in peak time jitter covariance with respect to base separation. Both peak amplitude and peak width are modelled as being uncorrelated with those of adjacent bases. In the model, linear expressions are given to describe the growth in peak time jitter and peak width as a function of base position while other parameters, such as amplitude variance, are modeled by constants. Together, these results form a simple model which may be used in the derivation of new sequencing algorithms or in simulations for the testing of such algorithms. We suggest that the correlation of the peak times is related to the Kuhn length of the single-stranded DNA fragments.

Algorithms↗

PubMed1998

Identification of inbred mouse strains harboring genetic modifiers of mammary tumor age of onset and metastatic progression.

Metastasis is one of the most important and complex processes in human neoplastic disease. A large number of both positive and negative events must occur to permit a tumor cell to colonize a distant site successfully. To identify mouse strains that harbor dominant genetic modifiers of this process, a strain survey was initiated utilizing a transgenic mouse mammary tumor model that exhibits a high incidence of pulmonary metastases. The transgenic animal was bred to 27 different inbred strains of mice and scored for the metastatic organ tropism and metastatic density. Thirteen strains were identified that had a statistically significant reduction in the numbers of pulmonary metastases. In addition, 10 strains were identified that altered the kinetics of induction of the primary mammary tumor. These strains will likely provide useful model systems for the analysis of genetic interactions in the initiation and progression of mammary adenocarcinomas.

Age of Onset↗

PubMed1998

The covalent coupling of Arg-Gly-Asp-containing peptides to liposomes: purification and biochemical function of the lipopeptide.

With the advent of liposomes as drug carriers, there arises a need for efficient targeted delivery in vivo. Proteins coupled to liposomes usually yield heterogeneous products that are ill-defined both chemically and in terms of spatial orientation. We now report on the disulfide linkage to the surface of intact liposomes of a peptide representing one-half of a ligand-receptor pair. An RGD-motif-containing peptide was coupled to the phospholipid PDP-DOPE of the liposomes by a thiol-disulfide exchange. The resulting lipopeptides were amenable to definition by TLC, HPLC, and MS and found to be in a functional orientation allowing biochemical interaction with their receptor, the integrin glycoprotein IIb-IIIa.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1998

Enhanced interleukin-2 gene transfer immunotherapy of breast cancer by coexpression of B7-1 and B7-2.

The capability of B7-1 to augment the antitumor activity of some cytokines has been shown primarily for such cytokines as interleukin-12 (IL-12), IL-7, and to a lesser extent IL-2. In this study, we investigate the ability of B7-1 and B7-2 to augment the antitumor activity of IL-2. Considering the affinity of both molecules for CD28 (T cell receptor for B7-1 and B7-2), we postulated that their potential to augment IL-2 antitumor activity would be similar. Two murine transgenic adenocarcinoma models were chosen to investigate the activity of adenoviral vectors constructed to express either B7-1 and IL-2 or B7-2 and IL-2. Before administering the vector intratumorally to tumor-bearing mice, we determined the expression of B7-1, B7-2, MHC I, and MHC II on these tumor cells and demonstrated positive expression of only MHC I. Intratumoral injection of the vector expressing B7-1 and IL-2 resulted in complete regression of all tumors treated. In contrast, the vector expressing B7-2 and IL-2 was significantly less effective at regressing PyMT tumors, whereas both double recombinant vectors demonstrated similar levels of complete regression in the Neu (NDL 8142) model. Regressed mice were all protected for rechallenge in both models and demonstrated antigen-specific cytotoxic T lymphocytes (CTL) in the PyMT model. These findings indicate that the combination of IL-2 with B7-1 or B7-2 significantly enhances the antitumor activity of IL-2.

Adenocarcinoma↗

PubMed1997

Histological studies of gene-ablated mice support important functional roles for natural killer cells in the uterus during pregnancy.

Maternal lymphocytes having a large and granulated morphology accumulate at healthy implantation sites in normal mice. Insight into the functions of these cells has come from a previous study of two independent lines of mice deficient in natural killer (NK) cells. In pregnant Tg epsilon 26 mice, vascular pathology was found that led to the major complications of either fetal death or intrauterine growth retardation. In pregnant p56lck null x IL-2R beta null mice, extensive distension of the decidua was observed that separated the placenta from the myometrium and appeared to be interstitial edema. To strengthen assignment of uterine large granulated lymphocytes to the NK cell lineage and to understand which aspects of NK cell biology may be important for a uterine-based, pregnancy-associated subset, mid-gestation implantation sites from a new series of mice having gene deletions which alter NK cells (IL-2R gamma null, Stat4 null, IL-12 p40 null, beta 7 integrin null and Muc-1 null) have been examined histologically. The findings support the assignment of pregnancy-associated large granulated cells of mice to the NK cell lineage and suggest that the primary functions of these tissue-based NK cells are to support normal development of the decidua and/or its vasculature using pathways that involve IL-12 mediated signal transduction.

Animals↗

PubMed1997

Functional analysis of mouse keratin 8 in polyoma middle T-induced mammary gland tumours.

Keratin 8 and 18 are commonly used as tumorigenic markers for various types of carcinomas. They are known to be involved in cell migration, cell invasiveness, plasminogen activity and drug and radiation resistance. To ascertain a potential function for simple epithelium keratins in mammary adenocarcinoma in vivo, keratin-8-deficient mice (mK8) were mated with transgenic mice carrying the middle T oncogene driven by the MMTV promoter. The resulting mK8 knockout and control progeny carrying the middle T transgene developed mammary gland tumours with the same incidence. However, the onset of palpable mammary gland tumours occurred earlier in mK8 mutant than in control mice. This effect was prominent in males where the onset in control animals is delayed overall, because of the lower hormonal inducibility of the MMTV promoter. Metastatic foci were observed in the lungs of all females and of a few males, independently of the genotype. Histological analysis revealed no morphological differences of the tumorigenic cells in primary tumours nor in metastatic foci. As expected, keratin 8 was absent in the mK8 tumours. Keratin 7 (mK7), keratin 18 (mK18) and keratin 19 (mK19) protein were observed in both primary and metastatic foci. These results constitute the first in vivo analysis of the role of simple epithelium keratins in mammary carcinogenesis. It demonstrates that the latency, but not the incidence nor the morphological features, of PyV middle T-induced mammary gland tumours is affected by keratin 8 deficiency.

Age Factors↗

PubMed1997

The effect of methotrexate and azathioprine on the serum levels of IgA-alpha 1-antitrypsin complex in juvenile chronic arthritis.

In the present study we investigated the influence of methotrexate (MTX) and azathioprine (AZA) on the serum levels of the IgA-alpha 1-antitrypsin (IgA-AT) complex in patients with the systemic form of juvenile chronic arthritis (JCA). Fifty-six JCA patients (22 treated with MTX, 18 treated with AZA, and 16 not treated with any immunosuppressive agent) were enrolled in the study. MTX dosage ranged from 0.3 to 0.5 mg/kg-1 week-1, while AZA was given daily at an average dose of 1 mg/kg. MTX was given for 13 months (SD = 7 months) whereas AZA for 11 months (SD = 6 months). The average value of the complex was higher in JCA patients than in both control groups (0.74 +/- 0.73 U vs 0.37 +/- 0.13 U (control children), P < 0.001 and vs 0.23 +/- 0.12 U (control adults), P < 0.001). Values exceeding the normal range were found in twenty-two JCA patients (39.4%). Serum IgA-AT level was lowest in the MTX group compared to AZA and non-treated patients (0.56 +/- 0.24 U, 0.76 = 0.43 U, 0.95 +/- 0.52 U, respectively, P < 0.05). IgA values exceeding normal levels for age were found in 14% of the patients. A correlation between the levels of the IgA-AT complex and C-reactive protein (r = 0.43, P < 0.01), alpha 1-acid-glycoprotein (r = 0.45, P < 0.01), alpha 1-antichymotrypsin (r = 0.52, P < 0.01), alpha 1-antitrypsin (r = 0.40, P < 0.01) and IgA (r = 0.56, P < 0.01) was established.

Adolescent↗

PubMed1996

Endemic Tyrolean infantile cirrhosis: an ecogenetic disorder.

BACKGROUND: 138 infants and young children died from an endemic infantile liver cirrhosis in a circumscribed rural area of western Austria between 1900 and 1974. Frequency of the disease peaked between 1930 and 1960. It has disappeared from this area since 1974. METHODS: Clinical and genetic data on the patients was gathered; pedigrees analysed and ethnographic studies and interviews were undertaken. FINDINGS: The disease, which was clinically and pathologically indistinguishable from Indian childhood cirrhosis and hepatic copper toxicosis, was transmitted by autosomal recessive inheritance. Cow's milk, contaminated with copper from untinned copper or brass vessels, may have contributed to the development of copper toxicosis. Replacement of untinned copper cooking utensils by modern industrial vessels has eradicated the disease. INTERPRETATION: Our findings strongly suggest that the endemic Tyrolean childhood cirrhosis-and by analogy non-Wilsonian hepatic copper toxicosis occurring elsewhere-is an ecogenetic disorder requiring the involvement of both genetic and environmental factors for the disease to become manifest.

Animals↗