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  • Articles: DFG German National Licenses  (16)
  • 1995-1999  (11)
  • 1975-1979  (5)
  • Life and Medical Sciences  (9)
  • Dopamine  (3)
  • ALCOHOLISM  (2)
  • General Chemistry  (2)
Source
  • Articles: DFG German National Licenses  (16)
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Years
Year
Keywords
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 63 (1979), S. 273-280 
    ISSN: 1432-2072
    Keywords: Dopamine ; Lateral inhibition ; Attention ; Schizophrenia ; Model for schizophrenia ; Schizophrenic symptoms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A hypothesis is briefly discussed proposing that schizophrenic symptoms are due to a breakdown in a mechanism by which conscious attention is limited and directed. It is shown that this mechanism can be modelled in terms of a simple nerve network in which every channel inhibits all the others. Failure of this inhibition would cause the defect hypothesised to occur in schizophrenia. It is shown that if dopamine is given a central role as transmitter in such a network then the various predictions about the biochemistry of schizophrenia that follow are not only consistent with the evidence for the ‘dopamine theory’ of schizophrenia, but also with much of the evidence held to be contrary to that theory. While not purporting to be an experimentally validated description of schizophrenia, this model goes beyond the single amine theories of schizophrenia and links dysfunctions in amine systems with specific behavioural control mechanisms. Given the current state of knowledge, such models can make only limited predictions about the biochemistry of schizophrenia. However, an attempt to link behavioural and biochemical systems in this way will be crucial for the development of viable animal models of schizophrenia.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Key words Methamphetamine ; Dopamine ; Serotonin ; Phentermine ; Fenfluramine ; Drug-discrimination ; Self-administration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To analyze the involvement of dopamine (DA) and serotonin (5-HT) release in the stimulus properties of methamphetamine, two amphetamine analogs that selectively release either brain DA (phentermine) or 5-HT (fenfluramine) were tested for their ability to substitute for methamphetamine in rats discriminating methamphetamine (1.0 mg/kg) from saline. They were subsequently tested for their ability to alter IV methamphetamine (0.06 mg/kg per injection) self-administration in the same species when given as a pretreatment. The DA releaser phentermine, like methamphetamine itself, decreased methamphetamine self-administration (to 70% of baseline responding), but only at a dose of 3.0 mg/kg that fully generalized to the methamphetamine stimulus in the discrimination study. The 5-HT releaser fenfluramine attenuated methamphetamine self-administration to a much larger extent than phentermine (to 37% of baseline responding) at a dose of 1.8 mg/kg that did not generalize to methamphetamine and did not decrease rate of responding in the discrimination study. Tolerance developed to the inhibitory effect of 1.8 mg/kg fenfluramine on methamphetamine self-administration when it was given repeatedly over four consecutive daily sessions. The fenfluramine-induced decrease in methamphetamine self-administration was also attenuated when it was given together with the small 1.0 mg/kg dose of phentermine. These results suggest that DA release plays a dominant role in the discriminative stimulus effects of methamphetamine. However, stimulation of 5-HT release can strongly modify methamphetamine self-administration.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: Key words Drug discrimination ; Microdialysis ; Dopamine ; Serotonin ; Phentermine ; Fenfluramine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Clinical case studies suggest that combined administration of the serotonergic agent fenfluramine (FEN) and the weak amphetamine-like anorexic agent phentermine (PHEN) may be useful in the treatment of alcohol and cocaine addictions. The present experiment examined the nature of the interaction between the two agonists using the drug discrimination paradigm. In vivo microdialysis served to examine the neurochemical profile of dopamine and serotonin release in the nucleus accumbens. In conscious rats, acute injections of FEN (1.0–2.0 mg/kg IP) or PHEN (1.0–2.0 mg/kg IP) selectively elevated levels of serotonin and dopamine in the nucleus accumbens, respectively. A mixture (1 mg/kg of each) increased levels of both amines by similar magnitudes to those observed with each individually. Three groups of Sprague-Dawley rats were trained to discriminate (1) FEN (1.0 mg/kg IP) alone, (2) PHEN (1.0 mg/kg IP) alone or a mixture (3) PHEN+FEN (1 mg/kg of each, IP) from saline under a fixed ratio (FR-10) schedule of food reinforcement. Rats acquired the mixture discrimination rapidly, while for the other groups the training dose had to be increased to 2.0 mg/kg to attain stimulus control. The individual components of the mixture at the training dose generalized partially to the mixture, and complete generalisation was observed following 3.0 mg/kg FEN or PHEN. Rats trained to discriminate the individual components showed respective cross-generalisation profiles. Generalisation to cocaine (0.3–10.0 mg/kg IP), amphetamine (0.1–3.0 mg/kg IP) and nicotine (0.1–0.8 mg/kg SC) was greatest in the MIX-trained rats, while partial or no generalisation was observed in rats trained to discriminate the individual compounds. From the present results, it may be concluded that the two drugs given as a mixture do not produce a novel cue. Rather, these aminergics appear to interact additively. Furthermore, the dual stimulation of the amines by the mixture may be the basis for the cueing effects of the FEN+PHEN drug mixture, and its effectiveness in treating drug addictions.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Digestive diseases and sciences 43 (1998), S. 1746-1751 
    ISSN: 1573-2568
    Keywords: ANTITHROMBIN III ; THROMBIN ; ACETALDEHYDE ; ALCOHOL ; ALCOHOLISM ; BLOOD COAGULATION
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The anticoagulant activity of antithrombin III(ATIII), as observed in a plasma-free system consistingof thrombin and fibrinogen, is readily reduced byacetaldehyde (AcH) at concentrations of 447, 89.4, and 17.9 mM. Whereas controlthrombin-fibrinogen mixtures clotted in 17.7 ±0.75 sec, ATIII prolonged clotting time to 55.0 ±1.75 sec on preincubation with thrombin for 30 min atroom temperature. On subsequent preincubation of ATIII with theAcH for 30 min at room temperature and passage of themixture through Sephadex G-25 minicolumns to removeexcess AcH, the eluates were tested for anticoagulant activity. Clotting times of 20.9 ± 1.0,32.3 ± 1.0, and 45.3 ± 1.6 sec wereobtained with 447, 89.4, and 17.9 mM AcH-ATIII mixtures,respectively. These data suggest that functional groupson ATIII, such as guanidiniums, aminos, and others aresusceptible to adduct formation with AcH, therebyaltering the shape and charge of the anticoagulant. Asa consequence of this type of reaction, an alteredmolecule of reduced biological activity may be produced.These experimental results may explain, in part, thereduction in ATIII levels reported by others in patientswith alcoholic liver disease.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Digestive diseases and sciences 44 (1999), S. 1349-1355 
    ISSN: 1573-2568
    Keywords: ANTITHROMBIN III ; THROMBIN ; HEPARIN ; BLOOD COAGULATION ; ACETALDEHYDE ; ALCOHOL ; ALCOHOLISM
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Acetaldehyde (AcH) at preincubationconcentrations of 447, 89.4, and 17.9 mM potentiates theeffects of heparin on the clotting time of plasma. Whilecontrol plasma clotted in the range of 12.6 ± 0.1 to 13.8 ± 0.1 sec, and heparin-treatedplasma clotted in a range from 131.5 ± 2.5 to168.2 ± 1.2 sec, heparin that was preincubated atroom temperature for 30 min with 89.4 or 447 mM AcH didnot clot plasma in 300 sec. Heparin exposed to 17.9 mMAcH clotted plasma in 193 ± 1.1 sec. Ethanol ata 404 mM concentration also prolonged the clotting timeof heparin-treated plasma 〉300 sec, while 202 mM ethanol prolonged the clotting time ofheparin-treated plasma from 149.0 ± 2.0 sec to219.5 ± 1.7 sec. It is suggested that AcH altersthe tertiary structure of heparin by adduct formation,possibly by formation of cyclic acetals with iduronicand glucuronic acids, thereby more readily affectingbinding of the glycosaminoglycan to antithrombin IIIand/or thrombin, prolonging clotting time. Ethanol, which does not react covalently with heparin,might affect its conformation as a consequence of anorganic solvent effect. Protamine sulfate prolonged theclotting time of plasma from 13.6 ± 0.1 sec to 17.9 ± 0.2 sec. Protaminesulfate-treated heparin clotted plasma in 21.0 ±0.4 sec relative to heparin-treated plasma (160.4± 1.7 sec). In subsequent experiments,AcH-treated protamine sulfate extended the clotting time of protamine sulfate from17.9 ± 0 sec to 33.7 ± 0.6 sec. Prioraddition of protamine sulfate to AcH- heparin mixturesor heparin to protamine sulfate-AcH mixtures beforeaddition to plasma resulted in clotting times of 22.0± 0.4 sec and 24.1 ± 0.5 sec,respectively, relative to control clotting times of162.3 ± 2.6 sec for plasma-heparin mixtures.These results confirm both the reduction in coagulation time ofheparin-treated plasma by protamine sulfate and theprolongation of clotting time of plasma by protaminesulfate. Furthermore, and importantly, they indicatethat acetaldehyde-treated protamine sulfate is a more effectiveanticoagulant than protamine sulfate. It is suggestedthat reversible adduct formation between acetaldehyde,heparin, and protamine sulfate may occur as a meansexplaining the essentially identical coagulation time ofthese mixtures when added to plasma regardless of theorder of premixing. Ethanol (404 mM) did not influenceprotamine sulfate effects. Lastly, the potentiation of the anticoagulant function of heparin byacetaldehyde suggests that a structural modification ofthe glycosaminoglycan may occur in alcoholics.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 183 (1975), S. 267-291 
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Seminiferous tubules from testes of normal and efferent ductule ligated mice were examined with the electron microscope. The tubules in the ligated animals were markedly distended and at most stages of the seminiferous cycle the epithelium exhibited a series of circumferentially-oriented ridges. Cross-sectional profiles of these ridges were studied with particular emphasis on the Sertoli cell junctional specializations and their relationship to the germinal cells.In the ligated specimen the basal cytoplasm of the Sertoli cells is highly attenuated, often appearing as a thin process resting on the basement lamina. Where the cytoplasm of one Sertoli cell ends, it meets in apposition with the cytoplasm of an adjoining Sertoli cell, and at these sites, junctional specializations are present. The ridges are comprised of a stalk of apical Sertoli cell cytoplasm, often appearing like an inverted cone, with young spermatids aligned along the lateral surfaces and the more mature spermatid population embedded within the apical cytoplasm. Junctional specializations were observed along these lateral Sertoli cell surfaces. In some instances, they formed a free surface, but usually early spermatids were in contact with the junctional specializations. With respect to the more mature spermatids, the acrosomal component was typically found in relation to a junctional specialization. Germ cells at the spermatocyte stage were also noted in relation to the Sertoli cell junctional specializations.The findings suggest that spermatocytes cross the Sertoli cell barrier and gain access to the adluminal compartment of the seminiferous tubule through the disengagement of the inter-Sertoli cell junctional complex. It is proposed that when the inter-Sertoli cell junctional specializations separate, the spermatocytes come in apposition with the newly freed junctional surfaces and remain in relation with them through the ensuing divisions. It appears that at some point, firm adhesion between germ cells and the junctional specializations occurs; the spermatid progeny may thus maintain contact with the original inter-Sertoli cell junctional specializations until their release into the tubule lumen.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 186 (1976), S. 79-103 
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The relationship between developing spermatids and Sertoli cell junctional specializations was studied with the electron microscope during spermiogenesis and at spermiation. At stage I of the seminiferous cycle, the newly formed spermatids are found in apposition to junctional specializations at the lateral surfaces of the Sertoli cell. Visualization of the junctional site of this early stage appears to be dependent on orientation and plane of section. As differentiation proceeds, the spermatids elongate and come to lie within deep recesses of the Sertoli cell. At this time the junctional specialization is limited to the acrosomal portion of the spermatid. During the maturation phase, the spermatids, while maintaining the same relationship to the junctional specialization, approach the lumen. When stage VIII of the cycle is reached, the stage in which spermiation occurs, the spermatids are at the luminal surface. The relationship of the spermatid head to the junctional specializations is quite variable during this stage. Some spermatids are observed still attached to the Sertoli cell at the junctional site, while others are found completely or partially surrounded by Sertoli cytoplasm, but with no evidence of the normally interposed junctional specialization. Yet, in other instances, the spermatids are observed in a position slightly removed from the junctional site. Also evident are profiles of junctional specializations at a free surface of the Sertoli cell, there being no attached spermatid. In some instances the junctional specializations appeared in apposition to a residual body. In the case of the free surface profiles, the junctional specialization at times lined an empty cleft or crypt-like recess, giving the impression that the spermatid head had just been dislodged from the junctional contact site. The findings indicate that the spermatid is in contact with a junctional specialization from its initial appearance and remains so until spermiation is initiated. It is postulated that spermiation is initiated through a physiological change in the junctional specialization resulting in loss of adhesion and consequent release of the sperm head from its attachment site. A similar mechanism is proposed in relation to the inter-Sertoli junctional complex to account for the means by which the spermatocytes cross this barrier to reach the adluminal compartment of the seminiferous epithelium.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 64 (1997), S. 390-402 
    ISSN: 0730-2312
    Keywords: carboxy-terminal repeat domain (CTD) ; RNA polymerase II ; cyclin-dependent kinases ; phosphorylation ; transcription ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Cdc2 kinase triggers the entry of mammalian cells into mitosis, the only cell cycle phase in which transcription is globally repressed. We show here that Cdc2 kinase phosphorylates components of the RNA polymerase II transcription machinery including the RNA polymerase II carboxy-terminal repeat domain (CTD). To test specifically the effect of CTD phosphorylation by Cdc2 kinase, we used a yeast in vitro transcription extract that is dependent on exogenous RNA polymerase II that contains a CTD. Phosphorylation was carried out using immobilized Cdc2 so that the kinase could be removed from the phosphorylated polymerase. ATPγS and Cdc2 kinase were used to produce an RNA polymerase 110 that was not detectably dephosphorylated in the transcription extract. RNA polymerase 110 produced in this way was defective in promoter-dependent transcription, suggesting that phosphorylation of the CTD by Cdc2 kinase can mediate transcription repression during mitosis. In addition, we show that phosphorylation of pol II with the human TFIIH-associated kinase Cdk7 also decreases transcription activity despite a different pattern of CTD phosphorylation by this kinase. These results extend previous findings that RNA polymerase 110 is defective in preinitiation complex formation. Here we demonstrate that phosphorylation of the CTD by cyclin-dependent kinases with different phosphoryl acceptor specificities can inhibit transcription in a CTD-dependent transcription system. J. Cell. Biochem. 64:390-402. © 1997 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 193 (1979), S. 23-41 
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: To further characterize Sertoli cell-germ cell junctional specializations seminiferous tubules from sexually mature Sprague-Dawley rats were dissociated by enzymatic and mechanical methods. Ultrastructural analysis of cell suspensions prepared by incubation in collagenase alone or by mechanical methods revealed that spermatids remained attached to Sertoli cells or Sertoli cell fragments. Such cellular associations were found only between Sertoli cell fragments and spermatids in which the developing acrosome had made contact with the plasma membrane (step 8 and subsequent steps of spermiogenesis). Furthermore, the fragments were confined to that region of the plasma membrane over the acrosome. The Sertoli cell half of this adhesive site displayed the typical elements of Sertoli cell junctions, filamentous bundles and associated cisterna of endoplasmic reticulum, in apposition to the spermatids. The spermatids demonstrated no surface specializations at the attachment sites. In contrast, in cell suspensions prepared with trypsin, spermatids were free of attachments to Sertoli cells or their fragments. These results demonstrate that: (1) the junctions act to bind cells together, (2) adhesive type contact is established between Sertoli cells and spermatids at step 8 and subsequent steps of spermiogenesis, (3) contact is restricted to the spermatid plasma membrane over the acrosome, and (4) spermatids can be freed from the junctional specializations by treatment with trypsin.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    American Journal of Anatomy 148 (1977), S. 49-55 
    ISSN: 0002-9106
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Seminiferous tubules, partially dilated by ligation of the efferent ductules, were examined after treatment with lanthanum. Lanthanum penetrated the intercellular spaces of the seminiferous epithelium, but only to the level of the Sertoli-Sertoli junctions. Further penetration from the interstitial surface of the tubule was restricted by membrane fusions (tight junctions) at the junctional complex. Lanthanum also penetrated the epithelium from the luminal surface permeating the adluminal intercellular spaces, including the site of the Sertoli-spermatid junction. The lanthanum occupying the Sertoli-spermatid junctional site appeared as a slightly narrower electron-opaque zone than that found in the non-specialized intercellular areas. The findings clearly reveal that only the Sertoli-Sertoli junctional site forms a restrictive barrier. In contrast to the specializations of plasma membrane which form the tight junction, the associated filaments and cisterna of endoplasmic reticulum may be components more directly related to maintaining and regulating cell adhesion.
    Additional Material: 4 Ill.
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