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  • 1
    Electronic Resource
    Electronic Resource
    Crystallization of the dimerization-initiation site of genomic HIV-1 RNA: preliminary crystallographic results (1999)
    Copenhagen : International Union of Crystallography (IUCr)
    Acta crystallographica 55 (1999), S. 281-284 
    Details
    ISSN: 1399-0047
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Notes: The genomic RNA of all retroviruses is encapsidated in virions as a dimer of single-stranded chains held together near their 5′-end. For HIV-1, the initial site of dimerization has been shown to be a hairpin with a nine-residue loop containing a self-complementary sequence of six residues. This structure is proposed to promote dimerization by loop–loop interaction and formation of a so-called `kissing complex'. A 23-nucleotide RNA strand containing the loop enclosed by a seven base-pair stem has been synthesized. This oligomer was crystallized by the vapour-diffusion method at 310 K, pH 6.5, with methyl-pentanediol as the precipitant agent in the presence of MgCl2, KCl and spermine. Quasi-complete diffraction data were obtained at 2.7 Å resolution with a conventional X-ray source and at 2.3 Å resolution on a synchrotron beamline. The space group is P3121 or its enantiomorph P3221, with cell parameters a = b = 60.1, c = 65.9 Å at ambient temperature, or a = b = 59.0, c = 64.3 Å in a nitrogen-gas stream. There are two oligomers per asymmetric unit as determined from absorbance measurements of a dissolved crystal whose volume was carefully determined. In some cases, either perfectly or partially twinned crystals were obtained. Perfect twinning is detected by an apparent hexagonal symmetry and yields unusable crystallographic data, whilst partial twinning yields usable data after adequate processing. Structure solution is under way by searching for heavy-atom derivatives and systematically substituting bromo- or iodo-uridines for uridines.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1107/S0907444998008506
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  • 2
    Electronic Resource
    Electronic Resource
    Heart valve dysfunction resulting from cellular rejection in a novel heterotopic transplantation rat model (2000)
    Springer
    Transplant international 13 (2000), S. S528 
    Details
    ISSN: 1432-2277
    Keywords: Key words Implantation model ; Aortic valves ; Valve dysfunction ; Rejection ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Structural failure of heart valve allografts may be related to technical factors or immunological reactions. To circumvent nonimmunological factors a new rat implantation model was developed to study whether alloreactivity results in histopathological changes and valve dysfunction. Syngeneic (WAG-WAG, DA-DA) and allogeneic (WAG-BN, WAG-DA) transplantation was carried out using this new technique, and the function of explanted valves was assessed 21 days later by retrograde comptence testing. Additionally, grafts were examined using standard histological and immunohistochemical techniques. There was no leakage during retrograde injection in nine of tem syngeneic and two of ten allogeneic grafts. Microscopically, syngeneic valves appeared normal without fibrosis or intimal thickening, although CD8+ lymphocytes and macrophages were found in necrotic myocardial rim and adventitia. In contrast, allogeneic valves were deformed and noncellular, with extensive infiltration of CD4+, CD8+ and CD68+ cells in adventitia and media. Absence of fibrosis and intimal thickening in syngeneic transplanted valves indicated circumvention of nonimmunological factors. Allogeneic valve transplantation induces cellular infiltration in the graft with subsequent graft failure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050395
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  • 3
    Electronic Resource
    Electronic Resource
    Cyclosporin A enhances locoregional metastasis of the CC531 rat colon tumour (1997)
    Springer
    Journal of cancer research and clinical oncology 123 (1997), S. 21-24 
    Details
    ISSN: 1432-1335
    Keywords: Cyclosporin A ; Growth promotion ; Metastasis ; Multidrug resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The immunosuppressive drug cyclosporin A has been evaluated recently in phase II trials in cancer therapy as a reverter of P-glycoprotein-mediated multidrug resistance. As an immunosuppressive agent, cyclosporin A potentially can enhance tumour growth. We investigated this potency of cyclosporin A in the weakly immunogenic CC531 colon adenocarcinoma model, using the same dose that had previously been shown to intensify the antitumour activity of doxorubicin in vivo. In vitro cyclosporin A caused no growth acceleration and only in high doses was growth inhibition of CC531 cells observed. In vivo no evidence of growth enhancement was found in short-term assays but, after 4 weeks, rats treated with cyclosporin A had a significantly higher tumour load, mainly consisting of locoregional metastases. These experiments in the CC531 tumour model show that cyclosporin A, used as a reverter of multidrug resistance, may produce short-term improvement of antitumour activity but may also induce enhancement of tumour metastasis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01212610
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  • 4
    Electronic Resource
    Electronic Resource
    Negligible role for NK cells and macrophages in delayed xenograft rejection (2000)
    Springer
    Transplant international 13 (2000), S. S504 
    Details
    ISSN: 1432-2277
    Keywords: Key words Xenotransplantation ; Macrophages ; NK cells ; Guinea pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Hyperacute rejection (HAR) of a discordant xenograft can be avoided by complement manipulation, but delayed xenograft rejection (DXR) still leads to graft loss. It is generally assumed that macrophages and NK cells play key roles in DXR. In the present study the survival times and cellular infiltrate following guinea pig to rat heart transplantation was analyzed in the course of DXR, following aspecific and specific manipulation of macrophages and NK cells. HAR was overcome by a single injection of cobra venom factor 1 day before heart transplantation. To aspecifically reduce the inflammatory response dominating DXR, dexamethasone (DEXA) was given. Treatment with DEXA markedly reduced infiltration by NK cells, macrophages, and granulocytes. It also led to prolonged graft survival times (median survival of 0.4 days, n = 10, P 〈 0.05). In the second series of experiments the specific roles of NK cells and macrophages in DXR were further assessed. Monoclonal antibody 3.2.3 was used to selectively deplete NK cells. Liposome-encapsulated dichloromethylene biphosphonate was given to achieve macrophage depletion. Neither of these specific treatments, alone or combined, led to prolonged graft survival. Immunohistology revealed that at day 2 after transplantation no NK cells or macrophages were present in grafts from the combined treatment group. Only a mild infiltration of granulocytes was observed. Collectively, these results strongly suggest that NK cells and macrophages are not likely to be pivotal cell types in DXR.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050391
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  • 5
    Electronic Resource
    Electronic Resource
    Laparoscopic surgery in the rat (1996)
    Springer
    Surgical endoscopy and other interventional techniques 10 (1996), S. 490-494 
    Details
    ISSN: 1432-2218
    Keywords: Laparoscopy ; Rat ; Tumor take ; Weight loss ; Pneumoperitoneum ; Bowel resection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The ability of laparoscopic techniques to treat malignant disease is controversial. We developed a rat model to assess metabolic and oncological effects of laparoscopic surgery. Methods: Experiment I. The postoperative body weight in 10 rats having laparoscopic bowel resection (group I), 10 rats having open bowel resection (group II) and 5 rats having anesthesia only (group III) was determined. Experiment II. Tumor take was scored in 11 rats having laparoscopic bowel resection (group IV), 11 rats having open bowel resection (group V), 6 rats having CO2 pneumoperitoneum without bowel resection (group VI) and 6 rats having anesthesia only (group VII). All rats had CC531 cancer cells injected intraperitoneally postoperatively. Results: Experiment I. Body weight loss in group I compared to group II (p〈0.036). Rats of group III lost no weight postoperatively. Experiment II. Tumor take was less in the subcutis (p=0.005), parietal peritoenum (p〈0.001) and bowel anastomosis (p=0.021) in group IV compared to group V. Tumor take was significantly greater at all sites except for subcutis in group VI compared to VII (all p〈0.022). Conclusions: Laparoscopic surgery is associated with less postoperative weight loss and less tumor take compared to open surgery. CO2 insufflation appears to increase tumor take.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00188392
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  • 6
    Electronic Resource
    Electronic Resource
    Laparoscopic surgery in the rat (1996)
    Springer
    Surgical endoscopy and other interventional techniques 10 (1996), S. 490-494 
    Details
    ISSN: 1432-2218
    Keywords: Key words: Laparoscopy — Rat — Tumor take — Weight loss — Pneumoperitoneum — Bowel resection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The ability of laparoscopic techniques to treat malignant disease is controversial. We developed a rat model to assess metabolic and oncological effects of laparoscopic surgery. Methods: Experiment I. The postoperative body weight in 10 rats having laparoscopic bowel resection (group I), 10 rats having open bowel resection (group II) and 5 rats having anesthesia only (group III) was determined. Experiment II. Tumor take was scored in 11 rats having laparoscopic bowel resection (group IV), 11 rats having open bowel resection (group V), 6 rats having CO2 pneumoperitoneum without bowel resection (group VI) and 6 rats having anesthesia only (group VII). All rats had CC531 cancer cells injected intraperitoneally postoperatively. Results: Experiment I. Body weight loss in group I compared to group II (p〈0.036). Rats of group III lost no weight postoperatively. Experiment II. Tumor take was less in the subcutis (p=0.005), parietal peritoenum (p〈0.001) and bowel anastomosis (p=0.021) in group IV compared to group V. Tumor take was significantly greater at all sites except for subcutis in group VI compared to VII (all p〈0.022). Conclusions: Laparoscopic surgery is associated with less postoperative weight loss and less tumor take compared to open surgery. CO2 insufflation appears to increase tumor take.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004649910096
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  • 7
    Electronic Resource
    Electronic Resource
    Laparoscopic vs conventional bowel resection in the rat (1998)
    Springer
    Surgical endoscopy and other interventional techniques 12 (1998), S. 412-415 
    Details
    ISSN: 1432-2218
    Keywords: Key words: Insulin-like growth factor — Laparoscopy — Bowel — Cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The role of laparoscopic surgery in the treatment of colorectal disease is still controversial. To assess the metabolic consequences of laparoscopic and open bowel surgery, we studied serum levels of insulin-like growth factor 1 (IGF-1), an anabolic and mitogeneic peptide, in rats. Materials and methods: In experiment 1, the serum IGF-1 levels of 10 rats undergoing laparoscopic small bowel resections (group I) and 10 rats undergoing conventional small bowel resections (group II) were determined before surgery and on days 1, 2, and 7. Experiment 2 compared five rats that had CO2 pneumoperitoneum (group III), five rats that underwent laparotomy (group IV), and five rats that received anesthesia only (group V). Differences in IGF-1 levels were tested with analysis of covariance. Results: In experiment 1, preoperative IGF-1 levels were similar in groups I and II (87.9 ± 6.1 nmol/L versus 90.5 ± 8.1 nmol/L). One day after surgery IGF-1 was 54.6 ± 10.5 in group I versus 41.6 ± 8.3 in group II (p= 0.006). Two days after surgery, IGF-1 was 79.4 ± 9.2 in group I versus 59.0 ± 10.5 in group II (p 〈 0.001). Seven days after both types of surgery, IGF-1 levels had returned to almost normal levels. In experiment 2, no significant differences were found between the rats with CO2 pneumoperitoneum (group III) and those with laparotomy only (group IV). Rats that had anaesthesia only showed a significant decrease in IGF-1 levels between days 0 and 1 (p 〈 0.018). Conclusion: Our study indicates that laparoscopic bowel surgery is associated with a better postoperative anabolic state (i.e., less catabolism) than conventional surgery. This finding reflects a potential benefit of laparoscopy in bowel surgery.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004649900693
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  • 8
    Electronic Resource
    Electronic Resource
    Port-site metastases after CO2 laparoscopy (2000)
    Springer
    Surgical endoscopy and other interventional techniques 14 (2000), S. 189-192 
    Details
    ISSN: 1432-2218
    Keywords: Key words: Aerosolization — Laparoscopy — Metastases — Pneumoperitoneum — Port site — Tumor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Animal experiments have shown that carbon dioxide (CO2) laparoscopy results in more port-site recurrences than gasless laparoscopy. Possible transport of aerosolized tumor cells by CO2 was investigated in rats. Methods: Abdominal cavities of 15 pairs of Wistar Agouti (WAG) rats were connected and 2 × 106 or 16 × 106 CC 531 cells were injected in the first (donor) rat of each pair. Then 10 l of CO2 were allowed to flow from the first (donor) to the second (recipient) rat. Results: No tumor was found in the recipients after injection of 2 × 106 cells in the donors. Injection of 16 × 106 cells in the donors resulted in very limited tumor growth in the recipients. Conclusions: Aerosolization of tumor cells occurs, but the number of intraperitoneal tumor cells required for metastases to occur by this mechanism is extremely high. Therefore, aerosolization of tumor cells appears not to be of major relevance in the pathogenesis of port-site metastases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004649900098
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  • 9
    Electronic Resource
    Electronic Resource
    Intraperitoneal tumor growth is influenced by pressure of carbon dioxide pneumoperitoneum (2000)
    Springer
    Surgical endoscopy and other interventional techniques 14 (2000), S. 817 -819 
    Details
    ISSN: 1432-2218
    Keywords: Key words: Carbon dioxide — Laparoscopy — Metastases — Pneumoperitoneum — Port site — Pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Several studies have indicated that the carbon dioxide (CO2) pneumoperitoneum during laparoscopy plays a role in the pathogenesis of port-site metastases. An experimental animal study was performed to investigate the impact of various pneumoperitoneum pressures on peritoneal tumor growth. Methods: In this study, 36 male WAG rats were randomized into three groups; two groups with different pneumoperitoneum pressures (16 mmHg and 4 mmHg) and one group of gasless controls. After a pneumoperitoneum of 0.5 × 106 ml was established, 531 tumor cells were injected intra-abdominally and the pneumoperitoneum was maintained for 60 min. Peritoneal tumor growth was assessed on day 11 at autopsy. Results: Peritoneal tumor growth in the 16-mmHg group was significantly greater than in the 4-mmHg group (p= 0.039) and the gasless group (p= 0.004). Conclusions: High-pressure CO2 pneumoperitoneum stimulates intra-abdominal tumor growth. The use of low insufflation pressures in laparoscopic cancer surgery should be considered.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004640010074
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  • 10
    Electronic Resource
    Electronic Resource
    Laparoscopic splenectomy and nephrectomy in a rat model (1997)
    Springer
    Surgical endoscopy and other interventional techniques 11 (1997), S. 491 -494 
    Details
    ISSN: 1432-2218
    Keywords: Key words: Laparoscopy — Rat — Model — Splenectomy — Nephrectomy — Tumor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: In experimental studies on the effects of laparoscopic procedures on tumor biology, a localized tumor model is desirable. The spleen and the kidney are preferable, because these organs are amenable to tumor placement and subsequent removal. This study describes the technique of laparoscopic splenectomy and nephrectomy in the rat model. Methods: Pneumoperitoneum was established by CO2 insufflation. Laparoscopic splenectomy involved two-handed dissection, intracorporeal ligation, and division of gastrosplenic attachments and hilar and short gastric vessels. Laparoscopic nephrectomy was done by intracorporeal ligation and division of the renal vessels and the ureter after mobilization of the kidney. Results: Laparoscopic splenectomy was performed in six rats; laparoscopic nephrectomy was done in six rats. Operative time ranged from 45 to 90 min for splenectomy and from 40 to 65 min for nephrectomy. Postoperatively, two rats died from hemorrhage. Necropsy of the rats after 10 days revealed adhesion in three rats after splenectomy and in four rats after nephrectomy. Inflammatory processes were found around the silk ligatures in all rats after splenectomy; in two rats wound infections occurred at the port sites. Conclusions: Laparoscopic splenectomy and nephrectomy in the rat proved technically feasible and may provide new localized tumor models suitable to be used in further studies on the oncological effects of laparoscopic surgery.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004649900400
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