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  • 1
    Electronic Resource
    Electronic Resource
    Genetic mapping of the embryonal carcinoma transplantation resistance locus Gt(B6) to mouse Chromosome 8 (1999)
    Springer
    Immunogenetics 49 (1999), S. 949-956 
    Details
    ISSN: 1432-1211
    Keywords: Key words Transplantation ; Histocompatibility ; Embryonal carcinoma ; Teratocarcinoma ; Mouse Chromosome 8
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Cytotoxic T lymphocytes play a predominant role in allograft rejection. They mediate this process through recognition of foreign major histocompatibility complex (MHC) class I surface molecules encoded at the H2 locus. Embryonal carcinoma cells, the undifferentiated, neoplastic derivatives of primordial germ cells, typically lack detectable MHC class I gene expression. Despite this, embryonal carcinoma cells are subject to allograft rejection in several different mouse strains. In many instances, the H2 locus appears to be genetically linked to resistance. However, rejection of allografts of the F9 embryonal carcinoma cell line, a nullipotent cell line derived from the 129 mouse strain, does not appear to be H2-linked. Resistance to F9 tumor formation in the C57BL/6 mouse strain has been attributed to a single, unidentified locus termed Gt(B6). To genetically map the Gt(B6) locus, a total of 463 (C57BL/6×129)F2 mice were challenged with F9 cells, and 78 tumor-resistant mice were identified. Markers encompassing two candidate regions, the H2 locus on Chromosome (Chr) 17 and a second candidate locus on Chr 2, showed no indication of linkage to the resistance phenotype. Instead, results of a genome wide scan implicated mouse Chr 8, and evidence is presented demonstrating that the Gt(B6) locus maps to a region of less than 10 cM on the medial portion of Chr 8.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050578
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  • 2
    Electronic Resource
    Electronic Resource
    Rewarding effort (1999)
    Oxford, UK and Boston, USA : Blackwell Publishers Ltd
    The @journal of political philosophy 7 (1999), S. 0 
    Details
    ISSN: 1467-9760
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Philosophy , Political Science
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/1467-9760.00083
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  • 3
    Electronic Resource
    Electronic Resource
    Transforming growth factor-β response and expression in junctional and oral gingival epithelial cells (1997)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of periodontal research 32 (1997), S. 0 
    Details
    ISSN: 1600-0765
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The junctional (JE) and oral gingival (OGE) epithelium show distinct morphological phenotypes and express different cell surface and keratin markers. Transforming growth factor-β (TGF-β) has been shown to stimulate extracellular matrix formation and inhibit proteolytic matrix degradation in periodontal wound healing. To elucidate potential roles of TGF-β in gingival epithelial regeneration and reattachement, the present study examined the effects of TGF-β on JE and OGE cell growth and determined the patterns of expression of mRNAs for the TGF-β isotypes β1, β2 and β3 and TGF-β receptor types I, II and III. Primary cell cultures were initiated from JE and OGE and the cell phenotypes confirmed using monoclonal antibodies to specific keratins. TGF-β induced a significant growth inhibition in OGE cells derived from 6 different patients with a mean inhibition of 46% and a range of 16–70% (p=0.031). Although responses varied between patients, in general maximum inhibition occurred at 10 ng/ml TGF-β. JE cells from 5 patients showed no significant growth inhibition by TGF-β (p=0.125). Greater expression of TGF-β2 and receptor type I mRNA was found in OGE than JE cells and thus appeared to be associated with differentiating epithelial cells. JE cells expressed more TGF-β type II receptor specific mRNA than did OGE cells, but TGF-β1 mRNA expression was similar in JE and OGE cells. JE or OGE cultures derived from 2 of 3 patients showed expression of mRNA for the TGF-β type III receptor. TGF-β3 mRNA was not detected in any of the JE or OGE samples examined. The greater sensitivity of OGE than JE to the growth inhibiting effects of TGF-β correlated with higher expression of receptor type I mRNA which, together with the type II receptor, is required for sensitivity to growth inhibition by TGF-β. The results suggest that, in addition to structural differences, the development of functional differences in the responses of JE and OGE to TGF-β may be associated with the formation of JE from OGE cells and the reformation of attachement after periodontal surgery.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1600-0765.1997.tb00579.x
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  • 4
    Electronic Resource
    Electronic Resource
    The replication checkpoint control in Bacillus subtilis: identification of a novel RTP-binding sequence essential for the replication fork arrest after induction of the stringent response (1999)
    Oxford BSL : Blackwell Science Ltd
    Molecular microbiology 31 (1999), S. 0 
    Details
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: We have shown previously that induction of the stringent response in Bacillus subtilis resulted in the arrest of chromosomal replication between 100 and 200 kb either side of oriC at distinct stop sites, designated LSTer and RSTer, left and right stringent terminators respectively. This replication checkpoint was also shown to involve the RTP protein, normally active at the chromosomal terminus. In this study, we show that the replication block is absolutely dependent upon RelA, correlated with high levels of ppGpp, but that efficient arrest at STer sites also requires RTP. DNA–DNA hybridization data indicated that one or more such LSTer sites mapped to gene yxcC (−128 kb from oriC ). A 7.75 kb fragment containing this gene was cloned into a theta replicating plasmid, and plasmid replication arrest, requiring both RelA and RTP, was demonstrated. This effect was polar, with plasmid arrest only detected when the fragment was orientated in the same direction with respect to replication, as in the chromosome. This LSTer2 site was further mapped to a 3.65 kb fragment overlapping the next40 probe. Remarkably, this fragment contains a 17 bp sequence (B′-1) showing 76% identity with an RTP binding site (B sequence) present at the chromosomal terminus. This B′-1 sequence, located in the gene yxcC, efficiently binds RTP in vitro, as shown by DNA gel retardation studies and DNase I footprinting. Importantly, precise deletion of this sequence abolished the replication arrest. We propose that this modified B site is an essential constituent of the LSTer2 site. The differences between arrest at the normal chromosomal terminus and arrest at LSTer site are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2958.1999.01299.x
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  • 5
    Electronic Resource
    Electronic Resource
    Effects of neuropeptide Y, insulin, 2-deoxyglucose, and food deprivation on food-motivated behavior (1995)
    Springer
    Psychopharmacology 120 (1995), S. 267-271 
    Details
    ISSN: 1432-2072
    Keywords: Neuropeptide Y ; Insulin ; 2-Deoxyglucose ; Food deprivation ; Motivation ; Reinforcer efficacy ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The current study demonstrates the ability of neuropeptide Y (NPY) to increase break points under a progressive ratio 1 (PR1) reinforcement schedule. An initial response resulted in delivery of a food reinforcer (45 mg pellet) under the PR1, and an additional response was required foreach successive reinforcer. The break point, the number of responses emitted to obtain the last reinforcer, is considered a measure of reinforcing efficacy or motivational strength of the food reinforcer. NPY (0.3–10 µg) significantly increased break point to levels comparable to those produced by 36–48 h of food deprivation. Although insulin (3–8 U/kg) and 2-deoxyglucose (150–250 mg/kg) also increased food intake, neither increased break points to levels produced by NPY or food deprivation. These data suggest that NPY may change the value of food in ways that cannot be accounted for by changes in insulin, glucose levels or intracellular glucoprivation. These results emphasize that simply measuring the amount of freely available food eaten is not a fully adequate measure of the strength of the feeding behavior.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02311173
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  • 6
    Electronic Resource
    Electronic Resource
    Naloxone effects on sucrose-motivated behavior (1996)
    Springer
    Psychopharmacology 126 (1996), S. 110-114 
    Details
    ISSN: 1432-2072
    Keywords: Motivation ; Naloxone ; Opioids ; Sucrose ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The opioid system plays an important role in feeding. In general, opioid agonists typically increase feeding and opioid antagonists decrease feeding in nonfood restricted animals. In food restricted animals the effects of these drugs are substantially reduced. Opioid antagonists have shown a marked effectiveness at reducing consumption of sweet foods. Explanations for this robust effect have typically focused on drug induced changes in taste, taste perception, or palatability. The current study relates the effects of the opioid antagonist naloxone on motivation to obtain different sucrose concentrations to the drug's effects on unrestricted sucrose solution consumption. Changes in motivation to respond were assessed under a progressive ratio reinforcement schedule (PR) which required increased response cost for each successive unit of sucrose solution. Motivation, as measured by the PR, increased as sucrose concentration increased and naloxone produced a dose-dependent decrease in motivation to respond for a given sucrose concentration. Thus, the effectiveness of naloxone was indirectly related to strength of the sucrose concentration. Under unrestricted access to sucrose solutions, naloxone reduced consumption greatest under the higher concentrations. The data suggest at least part of naloxone's effects on sweet tasting food may be mediated through endogenous opioid reward systems that are reflected in measures of motivation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02246345
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  • 7
    Electronic Resource
    Electronic Resource
    Naloxone administration following operant training of sucrose/water discrimination in the rat (1997)
    Springer
    Psychopharmacology 129 (1997), S. 289-294 
    Details
    ISSN: 1432-2072
    Keywords: Key words Discrimination ; Naloxone ; Opioids ; Taste ; Sucrose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The suppression of food intake observed following naloxone administration has often been ascribed to palatability or taste. Unfortunately, many confounds become apparent when attempts are made to isolate such factors in the investigation of ingestive behaviors. In the present study, rats (two groups) were trained to discriminate either a 10% or 5% sucrose solution from water (0.1 ml). These mildly food deprived subjects (95% of free-feeding weight) were trained to press the appropriate lever in a two-lever operant chamber following sampling of sucrose or water; successful responding was reinforced by delivery of a 45 mg grain food pellet. Following random exposure to reduced sucrose concentrations tested under extinction, a sucrose concentration gradient (1.0, 0.5, 0.1, 0.05, 0.01 and 0.005% sucrose solution) was established for both training groups under IP saline administration. Data collected under IP saline were then compared to those collected following random IP naloxone administration (3.0, 1.0, 0.3 and 0.1 mg/kg). No significant differences were observed between the sucrose concentration gradients obtained under saline and those obtained under naloxone, suggesting that the anorectic effect of naloxone is not primarily determined by discrimination of sweet taste.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050193
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  • 8
    Electronic Resource
    Electronic Resource
    Functions of the MDM2 oncoprotein (1999)
    Springer
    Cellular and molecular life sciences 55 (1999), S. 96-107 
    Details
    ISSN: 1420-9071
    Keywords: Key words. MDM2; p53; tumour suppressor; oncogene; autoregulatory feedback loop.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The p53 protein is activated in response to physiological stress resulting in either a G1 arrest of cells or apoptosis. As such, p53 must be tightly regulated, and the MDM2 oncoprotein plays a central role in that regulatory process. The transcription of the Mdm2 oncogene is induced by the p53 protein after DNA damage, and the MDM2 protein then binds to p53 and blocks its activities as a tumour suppressor and promotes its degradation. These two proteins thus form an autoregulatory feedback loop in which p53 positively regulates MDM2 levels and MDM2 negatively regulates p53 levels and activity. Immediately after ultraviolet (UV) irradiation MDM2 messenger RNA and protein levels fall in a p53-independent fashion, resulting in increased p53 levels. The p53 protein is then activated as a transcription factor by posttranslational modification permitting p53 to initiate its cell-cycle arrest or apoptotic (programmed cell death) functions. At later times, after the repair of DNA, MDM2 levels increase in a p53-dependent fashion. This induction of MDM2 results in the inhibition of p53 transcriptional activity and the degradation of p53 protein. MDM2-p53 complexes in the nucleus are transported to the cytoplasm via signals present in the MDM2 protein, where p53 is degraded in the proteasome. Thus MDM2 acts as a nuclear-cytoplasmic shuttle for the p53 protein. There are many levels at which this process is regulated, and as such there are many places for chemotherapeutic interventions. The amino-terminal domain of the MDM2 protein is all that is required to bind the p53 protein. The MDM2 protein has additional domains and therefore may have additional functions. Any of these MDM2 domains may contribute to MDM2's activities as an oncogene independent of its inhibition of the tumour suppressor functions of p53. Thus MDM2 itself could be a target for cancer therapeutic intervention.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s000180050273
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  • 9
    Electronic Resource
    Electronic Resource
    Lack of correlation between prostate-specific antigen density and prostatic shrinkage in response to finasteride therapy (1996)
    Springer
    World journal of urology 14 (1996), S. 360-362 
    Details
    ISSN: 1433-8726
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We attempted to correlate prostate volume reduction in response to finasteride treatment with initial prostate-specific antigen (PSA) levels and PSA density in men with symptomatic benign prostatic hyperplasia (BPH). The average reductions in prostatic volume (transrectal ultrasonography) were 27% and 34% after 6 and 12 months of finasteride therapy, respectively. Serum PSA levels decreased by 45% (6 months) and 50% (12 months). There was a positive correlation between initial serum PSA values and initial prostate volumes (r=0.57, P〈0.001). There was no correlation, however, between the initial serum PSA or PSA-density values and prostate volume reduction. These data indicate that initial serum PSA and PSA-density values are not predictive of the response to finasteride therapy in terms of prostate size reduction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00183115
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  • 10
    Electronic Resource
    Electronic Resource
    Interleukin-4 in the treatment of AIDS-related Kaposi's sarcoma (1997)
    Springer
    Annals of oncology 8 (1997), S. 79-83 
    Details
    ISSN: 1569-8041
    Keywords: AIDS-related Kaposi's sarcoma ; interleukin-4
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To define the safety and toxicity of interleukin-4 (IL-4)when administered subcutaneously in patients with AIDS-related Kaposi'ssarcoma (AIDS-KS); to evaluate the effect of IL-4 on immunologic and virologicparameters; and to preliminarily assess the response rate of IL-4 in AIDS-KS. Patients andmethods: Eighteen patients with mucocutaneous, non-visceral AIDS-KS weretreated with IL-4 at a dose of 1 mcg/kg subcutaneously, daily untilunacceptable toxicity or for a maximum period of six months. Twelve(66%) patients had extensive mucocutaneous disease with over 25lesions. Ten patients had received prior systemic chemotherapy. Seventeen hadCD4+ lymphocyte counts less than 200/mm3. Results: The most common adverse effects included headache in78%, fever in 56%, chills in 44%, and edema in44%. Hematologic toxicities consisted of grade 4 neutropenia (less than500/mm3) in 33%, mild anemia in 22%. Transientelevation of liver enzymes was noted in 17%. A transient elevation inCD4+ lymphocyte counts occurred during the first two weeks of therapy. Fourof eleven patients tested showed marked decline in plasma HIV RNA after fourweeks. Partial remission was observed in one patient, lasting six months.Three other patients (17%) had stable disease: 7 weeks in one patient,and 10 weeks in each of the two other patients. Conclusion: Grade 4 neutropenia (absolute neutrophil count〈500/mm3) was the most common hematologic adverse effectwith IL-4 in patients with AIDS-KS. In contrast to in vitro findings,there was a decrease in plasma HIV RNA after four weeks of IL-4 therapy in themajority of patients tested. IL-4 produced minimal anti-tumor effects inAIDS-KS with one partial remission in a patient with CD4 lymphocyte countsover 200/mm3. Further studies of IL-4 in AIDS-KS may beconsidered in patients with better immune status.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008205424763
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