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J Schmidt

Publications and source records attributed to J Schmidt.

At least 649 records · Page 36Linked to original sources
PubMed1986

Oncogenic retrovirus from spontaneous murine osteomas. II. Molecular cloning and genomic characterization.

An N-ecotropic murine leukemia virus (OA MuLV), originally isolated from spontaneous osteomas of strain 101 mice, was molecularly cloned. The virus induces osteomas, osteopetrosis, and malignant lymphomas in NMRI mice. The cloned virus was analyzed by heteroduplex analysis, restriction enzyme mapping, and oligonucleotide mapping. The data show a very close relationship to the endogenous Akv prototype virus with some differences in the gag and the env region. The nucleotide sequence of the U3 region of OA MuLV LTR revealed a structure within the presumable enhancer region very similar to the U3 sequences of the FBJ murine sarcoma virus and its associated helper virus. The significance of these specific structures for the oncogenicity of the virus and the development of the typical disease pattern is discussed.

Animals↗
PubMed1986

Differential effects of stimulation of the cat's red nucleus on lumbar alpha motoneurones and their Renshaw cells.

The red nucleus region was stereotaxically stimulated with short trains of high-frequency alternating current pulses in anaesthetized cats. The effects were studied, in contralateral lumbar segments, on the responses of microrecorded individual Renshaw cells (RCs) to antidromic or orthodromic test shocks of ventral root or muscle nerve fibres. Monosynaptic reflexes (MRs) of their motoneurone pools were recorded from one of the cut lumbar ventral roots. Averages of 10-20 replicate test responses of the RC (converted into instantaneous frequency curves, IFCs) and of the MR shapes were computed and graphically displayed. 2. Orthodromic (afferent) test shocks induced simultaneously MRs as well as responses of a RC belonging to the same motor pool. From their paired records at systematically varied shock strengths, whole "linkage characteristics" of the relation between the two events could be obtained, representing the functional linkage from the motoraxon collaterals to the RC under study. The overall result of rubral conditioning was a change in the course of the characteristic, which indicated a reduction of this linkage (= relative inhibition of the RC against its recurrent input). 3. Sequential trials with test shocks of constant, submaximal strength were performed with 45 individual RCs. The clearest results were obtained with RC responses to antidromic ventral root shocks: 65% of the RCs were partially inhibited by rubral conditioning. Interposed minor facilitory subcomponents could be seen in the course of inhibited IFCs. Mixed sequences of manifest inhibitory/facilitory effects were observed in 11%; reversed sequences (facilitory/inhibitory) did not occur. A pure but weak facilitation was found in only one case, paralleled by an increase of the MR. RCs belonging to either extensor or flexor motor pools were affected about equally. A little over 20% of the tested RCs remained uninfluenced by rubral stimulation. 4. The MRs, induced by constant, submaximal, orthodromic test shocks, were usually enhanced with only few exceptions, by rubral stimulation. The effects on the orthodromic RC responses were mainly inhibitory, but could be more or less masked by the concurrent increase of the MR, providing a stronger recurrent input to the RC. Such inhibition could be uncovered, however, by observing the above described linkage change. 5. Variation of several parameters of rubral conditioning (train duration, timing of train with respect to test shock, strength of train) modified the inhibitory effects on antidromic RC responses to a certain extent without changing their principal character.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Femoxetine and cimetidine: interaction in healthy volunteers.

The possibility of a pharmacokinetic interaction between femoxetine and cimetidine has been evaluated in 8 healthy volunteers. Two volunteers received single doses of femoxetine, and 6 were given multiple doses of femoxetine for 7 days with and without concurrent cimetidine. No influence of cimetidine was observed on the kinetics of single doses of femoxetine, but after multiple doses the plasma concentration of femoxetine was significantly increased. Similarly, the AUC at steady state tended to be increased, but not to a significant extent. Concurrent cimetidine did not cause a reduction in the AUC of the active desmethyl metabolite. It is recommended that femoxetine is given in reduced doses (e.g. 400 mg) when administered with cimetidine.

Adult↗
PubMed1986

Altered neurobiological responses to acute immobilization in social-isolated mice.

Social isolation results in dynamic changes of neurobiological functions. The altered internal state of the CNS is reflected in changes in spontaneous behavior, changed responses to transmission-related substances and changed responsiveness to an additional impairment of normal relations between the organism and its environment. We analysed the influence of an acute 2-hour immobilization on such isolation-dependent changes. Whereas the susceptibility to pentetrazole-induced seizures increased continuously with lengthening of isolation and was not affected by the additional impairment, the responsiveness to transmission-related substances changed dynamically depending upon isolation-induced alterations. An immobilization-induced increase in responsiveness to LSD and propranolol was demonstrable in grouped controls and after short-term isolation. The apomorphine stimulation during prolonged isolation experienced a down- and an upregulation which were repeated in a stronger manner by immobilization responses especially after long-term isolation. It is suggested that the dynamics of isolation-induced changes coincided with changed acute adaptive functions.

Animals↗
PubMed1986

Activation and biological properties of endogenous retroviruses in radiation osteosarcomagenesis.

The activation of endogenous retroviruses (MuLV) by internal irradiation and the presence of activated retroviruses in radiation-induced murine osteosarcomas as well as their biological properties in vivo and in vitro were studied. Ecotropic and xenotropic MuLV were expressed dependent on the radiation dose in spleen, bone marrow and bone tissues of C57Bl/6 mice after 224Ra treatment. Radiation-induced osteosarcomas of BALB/c, C57Bl/6 and C3H X 101/F1 mice harboured infectious ecotropic and/or xenotropic viruses whereas in osteosarcomas of NMRI mice predominantly virus protein could be detected. In about 50% of the radiation-induced osteosarcomas of BALB/c mice an amplification of ecotropic proviruses could be detected. This was not found in clonally grown cells from non-tumorous tissues. MuLV from radiation-induced osteosarcomas induced osteopetrosis, osteomas and lymphomas after infection of newborn NMRI mice. In differentiating bone tissue the viruses were found to infect predominantly osteoblast precursor cells suggesting that virus infection results in increased growth and metabolic activity of these cells, which may be a possible mechanism for their pathogenic action in bone tissues.

Animals↗
PubMed1986

Expression of the nodulation gene nodA in Rhizobium meliloti and localization of the gene product in the cytosol.

The nodA gene of Rhizobium meliloti encodes a 21.8-kDa protein, which is conserved in several Rhizobium species. We overproduced the nodA protein as a fusion product with a portion of the lambda cI repressor in Escherichia coli. This fusion protein was purified from inclusion bodies by gel and hydroxyapatite chromatography in the presence of NaDodSO(4). Monospecific polyclonal antibodies against the hybrid protein were used to detect the nodA protein in the cytosol of E. coli and R. meliloti by immunoblotting. In contrast to experiments with antibodies against the R. meliloti nodC membrane protein, the alfalfa-R. meliloti nodulation was not affected by the addition of anti-nodA antibodies to medium and inoculum. This suggests that the nodA protein is located within the cell and is therefore not accessible to antibodies. The expression of the nodA gene is induced in R. meliloti by various compounds present in the exudate of leguminous plants, particularly by the flavone luteolin. We show that the plant hormone trigonelline also has some inducing activity. The nodC protein was further localized in the membrane fraction of R. meliloti. Our experiments demonstrate that the nodC transmembrane protein is not necessary for the uptake of the compounds inducing the synthesis of the nodA protein. The nodA and the nodC proteins were also detected in mature nodules. During nodule development, the nodC protein may be processed to a 34-kDa protein.

Journal Article↗
PubMed1986

Effect of lectins on 3H-uridine and 3H-thymidine uptake by cultured renal cell carcinoma and normal renal cells.

The effect of lectins on cultured renal cell carcinoma and normal renal cells was studied. Ricin II showed effective inhibition of 3H-uridine and 3H-thymidine uptake by renal cell carcinoma and normal renal cells in all cases. Normal renal cells were more resistant to the inhibitory effect of ricin II as compared to renal cell carcinoma. Concanavalin agglutinin and wheat germ agglutinin led to stimulation of 3H-uridine and 3H-thymidine uptake by renal cell carcinoma and normal renal cells at low concentrations (0.2 micrograms/ml), and to suppression at high concentrations (2 and 20 micrograms/ml).

Carcinoma, Renal Cell↗
PubMed1986

Mechanism of action of a polypeptide neurotoxin from the coral Goniopora on sodium channels in mouse neuroblastoma cells.

Goniopora toxin (GPT), a polypeptide toxin of 9700 Da isolated from coral, markedly slows inactivation of sodium currents recorded under voltage clamp in mouse neuroblastoma cells. The voltage dependence of sodium channel activation is shifted to more negative membrane potentials by 9.8 +/- 2.1 mV, and the voltage dependence of channel inactivation is shifted to more positive membrane potential by 6.0 +/- 2.5 mV. These actions of GPT are voltage dependent with an e-fold increase in K0.5 for toxin action for each 48.3-mV depolarization between -80 and +40 mV. GPT requires Na+ or another alkali metal cation in the extracellular medium for its effect on sodium channels. The relative effectiveness of the different cations tested is Na+ greater than K+ greater than Rb+ greater than Li+ greater than Cs+ much greater than choline+. Like other polypeptide neurotoxins that slow inactivation of sodium channels, GPT enhances persistent activation of sodium channels by veratridine. However, GPT does not block the binding of 125I-labeled Leiurus scorpion toxin to neurotoxin receptor site 3 on sodium channels at concentrations which effectively slow channel inactivation. Therefore, our results define a new site on the sodium channel at which specific effects on inactivation can occur.

Action Potentials↗
PubMed1986

Morphology and in vivo growth characteristics of an atypical murine proliferative osseous lesion induced in vitro.

Mandibular condyles of late embryonic NMRI mice were used to study the effect of the FBR murine osteosarcoma virus in an in vitro tissue culture system. Chondroprogenitor cells and chondroblastic cells present in the condylar tissue normally undergo rapid differentiation in vitro which results in an advanced stage of bone formation. The infection of condyles with FBR murine osteosarcoma virus induced the transformation of bone progenitor cells and the formation of an atypical proliferative osseous lesion. In markedly disorganized tissue many spindle-like cells, giant cells, and pleomorphic cells were seen together with the formation of large bone spicules and the heavy mineralization of osteoid-like material and of the remaining cartilage. Fibroblast-like cells were found to penetrate from the perichondrial zone into the condylar mass and also into the underlying collagen sponge. The in vivo growth characteristics of FBR murine osteosarcoma virus-infected condyles after 3 days in culture were studied via s.c. transplantation into syngeneic mice. Control condyles developed normal trabecular bone, whereas the infected condyles induced a strong cellular response with the presence of atypical cells and newly formed connective tissue and bone in situ. These observations raise the possibility of a novel approach for further investigations related to numerous aspects of virus-induced osteosarcomagenesis.

Animals↗
PubMed1986

Retrovirus-induced osteopetrosis in mice. Ultrastructural evidence of early virus production in osteoblasts and osteocytes.

Newborn female strain NMRI mice were given injections of a mouse retrovirus (OA MuLV) known to induce osteopetrosis, osteoma, and lymphoma. Femur metaphyses and lumbar vertebrae were investigated ultrastructurally 3 d, 7 d and 28 d after infection. Budding, immature and mature virus was observed associated with osteoblasts and osteocytes, but not with osteoclasts or chondrocytes, 28 d after infection with the virus. No production of virus particles was observed in bone-tissue in mock-treated controls. Thus, the primary target cell for OA virus in bone appears to belong to the osteoblastic/osteocytic cell lineage.

Animals↗
PubMed1986

Lithium suppresses seizure susceptibility in pentylenetetrazol-kindled rats.

With regard to the still debatable effect of lithium in epilepsy the effect of chronic lithium treatment on the development of pentylenetetrazol(PTZ)-kindling and the anti-convulsive potency of acute lithium administration on PTZ-induced seizure behaviour in PTZ-kindled and non-kindled rats was examined. Lithium significantly suppressed the development of PTZ-kindling. In kindled rats the acute application of lithium reduced seizure susceptibility in a dose-dependent manner. In contrast to kindled rats, in non-kindled animals lithium had very weak anticonvulsive potency. The results suggest that lithium may be of potential interest in the treatment of special forms of epilepsy and epileptic brain disorders.

Animals↗
PubMed1986

Postnatal administration of L-dopa normalizes hypoxia-induced long-term changes in dopamine release from striatum slices and in avoidance learning.

Newborn rats exposed to a mild chronic postnatal hypoxia always displayed at the age of 2-3 months an increased fractional efflux rate of dopamine (DA) from striatum slices combined with a decreased capacity for learning and retention. The protective effect of the administration of L-DOPA on these long-term changes was tested by the injection of L-DOPA 5-30 min prior to the beginning of daily exposure to hypoxia. L-DOPA administration during postnatal hypoxia prevents in a dose dependent manner the long-term effects of postnatal hypoxia as described. This finding supports the hypothesis that long-term changes in DA release and in behaviour due to early postnatal hypoxia may be brought about by changes in the DA-metabolism during a critical period of development.

Animals↗