bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal Serum Levels of Human Chorionic Somatotropin Correlates with Transferrin and Erythropoietin in Pregnancy
Authors: Carretti Nicola , la Marca Antonio
Published: April 2003

During pregnancy, plasma levels of erythropoietin (EPO) and transferrin (TSF) show a gradual increase till term, when a slight decrease occurs. Human chorionic somatotropin (hCS) is a peptide hormone with a direct effect on the function of the syncytiotrophoblast and on the mass of functional placental tissue. In order to understand the relationships between the placental functions, maternal erythropoiesis and iron transfer to the fetus, the relationships between EPO and hCS and between TSF and hCS were investigated. A group of healthy pregnant women (n = 190) attending the Obstetric Clinic of the University of Siena were studied. They were between 18 and 43 weeks pregnant. A single blood sample was taken from each patient by radial vein puncture on admission into the clinic before the beginning of any therapy, for the determination of haemoglobin, EPO, ferritin, serum iron, TSF and hCS. The highest correlation was that between hCS and TSF (r = 0.336, p < 0.0001). This correlation was significant in anaemic patients and lost its significance in non-anaemic patients. In our study, we also found a significant relationship between hCS and logEPO (r = 0.195; p < 0.01) which reached an elevated significance over the entire survey, but did not reach statistical significance in anaemic women. We hypothesise that in pregnancy chorionic villi develop a great capacity to respond to pathological maternal events with the result of regulating the transport of iron, the oxygen tension and the maternal-fetal transfer of oxygen through haemoglobin. Evidently, the response of the villi serves to balance the lack of iron in favour of the fetus, probably through a mechanism that links the variations of the iron transport on the maternal side and the increased use on the fetal side through a dynamic and consensual response by the chorionic villi.
Role of Cytokines in Endometriosis-Associated Infertility
Authors: Iwabe Tomio , Harada Tasuku , Terakawa Naoki
Published: April 2003

Endometriosis, which is common in women of reproductive age, may affect fertility. It is also clear that mechanical disruption of the pelvic anatomy may cause infertility. However, our understanding of the association between the early stage of endometriosis and infertility remains incomplete. Bloody peritoneal fluid (PF) is frequently observed in the cul-de-sac of endometriosis patients and contains various biologically active factors. We found that the concentrations of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in PF from patients with endometriosis were significantly higher than that of patients with endometriosis. There were significantly positive correlations between the levels of TNF-α and IL-6. We compared the levels of these cytokines with regard to the R-AFS stages and scores, but no differences were observed. In contrast, these cytokines correlate with the number and extent of red color peritoneal endometriosis. TNF-α increased the expression of IL-6 messenger RNA and protein in endometriotic stromal cells derived from chocolate cyst in a dose-dependent manner. The addition of IL-6 inhibited the development of mouse preimplantation embryo and impaired sperm function. We concluded that increased levels of IL-6 in peritoneal fluid of patients with active red endometriosis might be related to endometriosis-associated fertility.
Influence of Pelvic Endometriosis and Ovarian Endometrioma on Fertility
Authors: Fujishita Akira , Khan Khaleque Newaz , Masuzaki Hideaki , Ishimaru Tadayuki
Published: April 2003

We investigated the influence of pelvic endometriosis and ovarian endometrioma on pregnancy outcome in women associated with infertility. A total of 237 women with endometriosis were reviewed, and their fertility rate was assessed by both r-AFS staging and TOP classification as previously proposed by our group. There was no significant difference in pregnancy rate among r-AFS stages. However, the pregnancy rate was mostly affected by the tubal condition according to the TOP classification as follows: no adhesive lesion (T₀), 53% (69/129); unilateral lesion (T1), 46% (18/39); bilateral lesion with at least one tube patent, (T2), 37% (10/27); bilateral tubal occlusion (T3), 0% (0/8) (p < 0.05, Mantel-Extension test). The absence (O₀–O1) or co-existence (O2–O3) of ovarian endometrioma and different gradings of cul-de-sac obliteration (P2–P3) showed no significant differences in pregnancy rate. The resulting conception rate was also not affected by the size or location of ovarian endometrioma. In addition, the higher adhesion score of ovarian endometrioma involving the fallopian tube and as described in r-AFS classification had a significant detrimental effect on fertility. These observations suggest that our TOP classification describing individual tubal condition has a clinically predictive value in assessing the reproductive outcome of women with endometriosis.
Comparison of Ondansetron with Metoclopramide in the Symptomatic Relief of Uremia-Induced Nausea and Vomiting
Authors: Ljutić Dragan , Perković Dijana , Rumboldt Zvonko , Bagatin Jugoslav , Hozo Izet , Pivac Nediljko
Published: April 2003

Background: Nausea and vomiting are well-known gastrointestinal complications in chronic renal failure and are frequent indications for the commencement of dialysis. Although the administration of antiemetic drugs (metoclopramide and, recently, ondansetron) is usually mentioned, there are scanty data on their effects. Methods: A double-blind crossover study was done in 10 uremic patients. All the patients were uremic and suffered from nausea and vomiting. The drugs were randomly administered intravenously (either metoclopramide 10 mg or ondansetron 8 mg) 2 h after blood drawing for laboratory tests either on the 1st or on the 3rd study day at the same time. The outcomes were scored after 24 h of follow-up by (1) one of us (D.P.; 1–3 points: 1 = no effect; 2 = moderate effect – decreased frequency of vomiting, and 3 = good effect – no vomiting), and (2) by the patients (1–5 points). Results: The results obtained showed that ondansetron was more effective in controlling nausea and vomiting than metoclopramide, either objectively (2.80 ± 0.422 vs. 1.40 ± 0.699, p < 0.005) or subjectively (4.10 ± 0.738 vs. 2.10 ± 0.994, p < 0.005). Conclusions: We conclude that at the dosage level studied ondansetron is about twice as effective as metoclopramide in the symptomatic relief of uremia-induced nausea and vomiting.
Gynäkologisch-geburtshilfliche Rundschau – zukunftsweisend und praxisnah
Authors: Haller U. , Hepp H. , Winter R.
Published: April 2003

Nach 15 Jahren Unterbruch hat die Schweizerische Gesellschaft für Gynäkologie und Geburtshilfe (SGGG) die Organschaft der ‘Gynäkologisch-geburtshilflichen Rundschau‘ wieder aufgenommen. Damit ist auch ein Signal für eine intensivere Zusammenarbeit mit der Österreichischen Gesellschaft für Gynäkologie und Geburtshilfe gesetzt. Vielleicht lässt sich dadurch auch die Bayerische Gesellschaft für Gynäkologie und Geburtshilfe gewinnen, Gleiches zu tun. Verlag und Herausgeber stellen sich im Zeichen der stürmischen Entwicklung im Bereiche der Printmedien erneut den veränderten Herausforderungen. Das Konzept der Zeitschrift wird an die modernen Anforderungen der Leserschaft angepasst, und so werden neben den traditionellen Originalartikeln, die für den Impact-Faktor entscheidend sind, weitere Sparten wie z.B. Medizin und Recht, Managementfragen im Gesundheitswesen, Kongressberichte usw. eingerichtet. Wie bisher können Publikationen in deutscher und englischer Sprache erscheinen.
Chemotherapieassoziierte Myelosuppression in der gynäkologischen Onkologie
Authors: Janni W. , Rjosk D. , Strobl B. , Bergauer F. , Linka F. , Dimpfl T. , Schindlbeck C. , Rack B. , Kaestner R. , Sommer H.
Published: April 2003

Einleitung und Fragestellung: Durch die Dosisintensivierung und durch den Einsatz von neuen Substanzen wird zunehmend häufig eine klinisch relevante Myelosuppression durch adjuvante Chemotherapieschemata beobachtet. Häufig wird die Einschätzung der zu erwartenden Zytopenie durch den Mangel an direkt vergleichbaren Daten erschwert. Ziel der vorliegenden Arbeit war es, die chemotherapieassoziierte Myelosuppression von vier in der gynäkologischen Onkologie gebräuchlichen Chemotherapieschemata im eigenen Patientengut zu vergleichen. Methode: Bei 79 Patientinnen mit primärem Mammakarzinom und 26 Patientinnen mit epithelialem Ovarialkarzinom wurde eine zytostatische Therapie durchgeführt und die damit assoziierte Myelosuppression durch Erfassung der Zytopenie und der Notwendigkeit zur supportiven Therapie evaluiert. Die untersuchten Chemotherapieschemata umfassten das CMF-Schema (Cyclophosphamid 600 mg/m2, Methotrexat 40 mg/m2, 5-Fluorouracil 600 mg/m2, 6×q3w), das EC/CMF-Schema (Epirubicin 90 mg/m2, Cyclophosphamid 600 mg/m2, 4×q3w, gefolgt von CMF, 3×q3w), das DE-Schema (Docetaxel 75 mg/m2, Epirubicin 90 mg/m2, 6×q3w) und das CC-Schema (Cyclophosphamid 600 mg/m2, Carboplatin AUC 6, 6×q3w). Ergebnisse: Die Schemata EC/CMF und DE wurden signifikant häufiger bei fortgeschritteneren Tumorstadien durchgeführt, jedoch fanden sich keine Unterschiede in tumorbedingter, prächemotherapeutischer Myelosuppression. Die stärkste Beeinträchtigung der Hämatopoese fand sich in der CC-Gruppe mit einem durchschnittlichen Abfall des Serumhämoglobins von 1,5 g/dl bis Ende der zytostatischen Therapie. In dieser Gruppe wurden entsprechend die meisten Erythrozytenkonzentrattransfusionen nötig. Die stärkste Suppression der Leukopoese war in der DE-Gruppe mit einem durchschnittlichen Leukozytenabfall von 6,2 × 103/µl pro Zyklus zu verzeichnen; in dieser Gruppe wurden im Mittel 7,6 Fertigspritzen mit 263 µg Lenogastrim zur Leukopoesestimulation verabreicht. Der stärkste Abfall der durchschnittlichen Thrombozytenzahl fand sich mit 171,7 × 103/µl in der CC-Gruppe. Schlussfolgerung: Das CC-Schema führt zur stärksten Beeinträchtigung der Thrombo- und Erythropoese, während das DE-Schema zu einer ausgeprägten Leukopenie führt. Das Schema mit der geringsten Myelosuppression war das CMF-Schema. In keinem der untersuchten Fälle kam es zu einer schweren zytopenieassoziierten Komplikation.
The Effect of Heat-Inactivated Helicobacter pylori on the Blastogenic Response of Peripheral Blood Mononuclear Cells of Patients with Chronic Urticaria
Authors: Hidvégi Bernadett , González-Cabello Rhenso , Temesvári Erzsébet , Szentmihályi Anna , Nagy Eszter , Fekete Béla , Marschalkó Márta , Horváth Attila , Gergely Péter
Published: April 2003

Background:Helicobacter pylori, the most important etiologic factor of gastritis and peptic ulcer, has recently been associated with several extradigestive diseases. Previous studies reported conflicting results on H. pylori eradication in chronic urticaria, in that some studies showed a benefit, while others found no effect. Methods: Peripheral blood mononuclear cells of 24 chronic urticaria patients (13 seropositive/11 seronegative for H. pylori) and 18 healthy controls (9 seropositive/9 seronegative) were stimulated with whole heat-inactivated H. pylori (8 × 105, 8 × 106 and 8 × 107 bacteria/well), phytohemagglutinin (2 µg/ml) and pokeweed mitogen (5 µg/ml). The proliferative response was determined by 3H-thymidine incorporation. Helicobacter-specific IgG antibody response was determined by ELISA. Results: There were significantly higher proliferative responses to various concentrations of whole heat-inactivated H. pylori antigen in 6- to 7-day cultures of peripheral blood mononuclear cells of chronic urticaria patients compared to healthy controls. We found a tendency to exhibit a higher proliferative response to either Helicobacter antigens or mitogens in seropositive compared to seronegative patients. Conclusion: Our results support the hypothesis that there is an increased lymphocyte reactivity in chronic urticaria, perhaps further enhanced by the presence of H. pylori which, therefore, may be involved as a trigger in the pathogenesis of chronic urticaria.
Role of Interleukin-17 and the Neutrophil in Asthma
Authors: Lindén Anders
Published: April 2003

Recent clinical evidence shows that acute, severe exacerbations of asthma are associated with recruitment and activation of neutrophils in the airways. There is also experimental evidence from rodents that T-lymphocytes are involved in the recruitment of neutrophils following allergen challenge in sensitised airways. This review addresses the potential role of neutrophils and the cytokine interleukin-17 (IL-17) in severe asthma. IL-17 is produced and released as a free protein from T-lymphocytes of the memory (CD45RO+) subset. Evidence from rats in vivo suggests that IL-17 can recruit and activate neutrophils in the airways; the recruitment is mediated by the rat correlate to the neutrophil chemoattractant interleukin-8 (IL-8) macrophage inflammatory protein-2 (MIP-2). Endogenous peptidases modulate neutrophil recruitment by acting on NK-1 receptors in rat airways in vivo. Human bronchial epithelial cells in vitro respond to stimulation with IL-17 by increasing the production and release of the human neutrophil chemoattractant IL-8. This release of IL-8 is functionally significant; it causes neutrophil chemotaxis in vitro. Furthermore, this IL-8 release is sensitive to a glucocorticoid and is potentiated by the pro-inflammatory cytokine, tumour necrosis factor-alpha (TNF-α) in vitro. In addition, IL-17 stimulates human bronchial epithelial cells in vitro to release the neutrophil-activating factor IL-6. This effect of IL-17 on IL-6, and IL-8 is in part mediated via mitogen-activated protein kinases. In conclusion, as indicated in rat airways in vivo and in human bronchial epithelial cells in vitro, IL-17 may constitute a link between the activation of certain T-lymphocytes and mobilisation of neutrophils in the airways, via induced release of C-X-C chemokines and tachykinins. Further studies are required to answer the question whether free, soluble IL-17 protein plays this role in the airways of patients with severe asthma.
Immunochemical Characterization of Two Pichia pastoris-Derived Recombinant Group 5 Dactylis glomerata Isoallergens
Authors: van Oort Erica , de Heer Pleuni G. , Lerouge Patrice , Faye Loïc , Aalberse Rob C. , van Ree Ronald
Published: April 2003

Background: Grass pollen of the Poaceae grasses are known to be highly allergenic. Major allergens from the species Lolium, Phleum, Poa and Holcus have been cloned and expressed as recombinant proteins, but of the important species Dactylis glomerata no recombinants are available. Methods: Dac g 5 was cloned by PCR on the basis of homology with Lol p 5 and expressed in Pichia pastoris. Recombinant Dac g 5 (rDac g 5) was affinity purified and compared to natural Dac g 5 (nDac g 5) by immunoblot, radioallergosorbent test (RAST), RAST inhibition, basophil histamine release assay (HRA), competitive radioimmunoassay (RIA) and sandwich enzyme-linked immunosorbent assay (ELISA). In addition, N-terminal sequencing, concanavalin A (Con A) binding, circular dichroism spectrum measurements and matrix-assisted laser desorption ionization-time of flight mass-spectrometric analysis were performed. Results: Clones were obtained that coded for pro-Dac g 5 and two mature isoforms of Dac g 5; the deduced amino acid sequences of both isoforms differed by 4 amino acids. Both mature isoforms were expressed in Pichia at a concentration of ∼15 mg/l. SDS-PAGE analysis showed that rDac g 5 had an apparent Mr approximately 10 kD above nDac g 5. By mass spectrometry this difference was shown to be around 2.5 kD. Positive Con A staining suggested (O-linked) glycosylation as an explanation for this increase in Mr. Whereas both purified recombinants showed a tendency to dimerize, purified nDac g 5 contained a 12-kD peptide not observed for rDac g 5. RAST, RAST inhibition and HRA showed that the IgE reactivity of rDac g 5 was similar to that of nDac g 5. A small subgroup, however, clearly demonstrated decreased IgE reactivity to rDac g 5.02. Differences in immune reactivity of both isoforms were confirmed by monoclonal antibody (mAb)-based sandwich ELISA. Conclusions: Dac g 5 was successfully cloned and expressed in P. pastoris. Minor differences in primary structure between isoforms influence their immune reactivity.
The Stripped Basophil Histamine Release Bioassay as a Tool for the Detection of Allergen-Specific IgE in Serum
Authors: Kleine Budde Ilona , de Heer Pleuni G. , van der Zee Jaring S. , Aalberse Rob C.
Published: April 2003

Background: For the detection of allergen-specific IgE in serum, IgE-binding assays such as the radioallergosorbent assay (RAST) are commonly used. In this study, the applicability and sensitivity of the stripped basophil histamine release bioassay was investigated and compared to the RAST. Methods: Basophils were stripped of their IgE by an acidic buffer, sensitized by human serum and stimulated by allergen with or without interleukin (IL)-3. The histamine release was determined by fluorometric analysis. Results: We showed that for enhancement of the maximal histamine release and the sensitivity of the stripped basophil assay, the priming cytokine IL-3 can be added to the basophils simultaneously to the stimulus. Preincubation of the cells with IL-3, as described in other studies, was not necessary. The bioassay can be used to study the specificity of IgE-mediated reactions. Basophils sensitized by serum absorbed to a particular allergen did not respond to this allergen anymore. This method is very suitable to study cross-reactivity between allergens. The results obtained in the bioassay were comparable to those obtained in the RAST. Using the RAST, lower concentrations of allergen-specific IgE were detected than in the bioassay. However, sera containing IgE against minor allergenic components were negative in the RAST, but strongly positive in the basophil assay. Conclusions: The stripped basophil histamine release bioassay is useful to complement and extend serological detection of allergen-specific IgE. Especially with sera containing IgE against minor components, this assay is more suitable than the RAST. Furthermore, in this assay, the dependency of IgE and of allergen-specific IgE in reactions can be studied in more detail.
Endothelin-1 and Big-Endothelin Concentrations Are Elevated in Liver Graft Tissue during Cold Storage and Reperfusion
Authors: Kraus T. , Golling M. , Mehrabi A. , Fernandes L. , Angelescu Michaela , Gebhard Martha-Maria , Herfarth C. , Klar E.
Published: April 2003

Endothelin (ET) and its precursor big-ET were synchronously analyzed by RIA in liver biopsies and systemic plasma during porcine orthotopic liver transplantation (OLT) before graft harvesting (phase A), after cold storage (phase B), and early (phase C) and late reperfusion (phase D). Tissue and plasma concentrations were correlated with length of survival and reperfusion. Increased tissue ET/big-ET levels were already detected during phase B (ET: 46 ± 20; big-ET: 245 ± 119 pg/mg cytosolic protein) and remained elevated in phase C (ET: 49 ± 16; big-ET: 306 ± 144 pg/mg) compared to baseline (ET: 32 ± 13; big-ET: 185 ± 164 pg/mg; p < 0.05). In phase D, a rapid concentration decline was detected (ET: 36 ± 26; big-ET: 163 ± 138 pg/mg). Systemic ET levels were elevated in phase B (3.4 ± 3.0 pg/ml), C, (2.8 ± 1.2 pg/ml) and D (2.6 ± 2.0 pg/ml), compared to baseline (1.7 ± 1.1 pg/ml; p < 0.05). ET/big-ET kinetics in liver tissue and systemic plasma showed analogous characteristics. Intrahepatic ET accumulation during storage and early reperfusion could be of relevance for harvest-related disturbances of hepatic microcirculation.
Expression of Bcl-2 Family Reduces Apoptotic Hepatocytes after Excessive Hepatectomy
Authors: Kamimukai N. , Togo S. , Hasegawa S. , Kubota T. , Kurosawa H. , Li X.-K. , Suzuki S. , Shimada H.
Published: April 2003

Excessive hepatectomy often causes fatal hepatic failure, but the mechanism is unknown. We used a novel protocol of partial 90 and 95% hepatectomy (PHx) to investigate this mechanism in 2 groups of rats. The 90% PHx rats survived, but the 95% PHx animals died of hepatic failure. In the latter, cytokine (interleukin-6, tumor necrosis factor-α) levels and the apoptotic hepatocyte count increased, and there were few mitotic cells. By contrast, in the 90% PHx rats, the mitotic cell count increased, and more anti-apoptotic Bcl-xL protein was expressed. These results demonstrate that expression of Bcl-xL protein as an anti-apoptotic factor or regeneration factor contributes to survival after 90% PHx. Using an adenovirus vector, the human bcl-2 gene (hbcl-2) was therefore transfected to DA rat livers where it was efficiently expressed, and then 95% PHx was performed. Liver damage was decreased and the apoptotic cell count decreased too, but the rats died. We concluded that transfection of the hbcl-2 gene partly prevents cytotoxicity (apoptosis), but cannot ensure survival. Thus, some other factor is required (e.g., a regeneration stimulator) to maintain life in these models.
Glycosaminoglycans of Normal Veins and Their Alterations in Varicose Veins and Varicose Veins Complicated by Thrombophlebitis
Authors: Wolańska Małgorzata , Sobolewski K. , Głowiński S. , Kowalewski R. , Płoński A.
Published: April 2003

The aim of the study was to examine the content and molecular differentiation of glycosaminoglycans (GAGs) in the wall of varicose veins. The studied material consisted of normal, varicose veins and varicose veins complicated by thrombophlebitis collected during operations on 26 patients. In the wall of varicose veins the mean GAGs’ content as well as the content of sulphated GAGs, except heparan sulphate was increased, whereas the amount of hyaluronic acid was decreased. Furthermore, the increased quantitative ratio between sulphated and nonsulphated GAGs was demonstrated. The results indicate an evident extracellular matrix remodelling in the wall of varicose veins particularly those complicated by thrombophlebitis, that is characterised by alterations in the content and molecular differentiation of GAGs.
Effect of CO2 Pneumoperitoneum on the Systemic and Peritoneal Cytokine Response in a LPS-Induced Sepsis Model
Authors: Matsumoto T. , Dolgor B. , Ninomiya K. , Bandoh T. , Yoshida T. , Kitano S.
Published: April 2003

We studied the effect of carbon dioxide (CO2) pneumoperitoneum on the systemic and peritoneal cytokine response in a rat model of intraperitoneal sepsis. After intraperitoneal injection of bacterial lipopolysaccharide (LPS, 10 mg/kg), rats were divided into 3 groups (n = 49 in each group): control (abdominal puncture); CO2 pneumoperitoneum, and laparotomy. Blood and peritoneal lavage fluid (PLF) were sampled at 0, 1, 2, 3, 4, 6, and 8 h after LPS challenge. Blood cell counts, plasma endotoxin level, and the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the plasma and PLF were measured. Blood cell counts did not differ between the 3 groups. Plasma endotoxin levels in the pneumoperitoneum group were significantly increased immediately after the procedure (p < 0.05). Although peak plasma TNF-α levels in the pneumoperitoneum group were seen immediately after the procedure, other changes in plasma cytokine levels did not differ significantly between the 3 groups. PLF TNF-α and IL-1β levels in the pneumoperitoneum group were significantly lower than levels in the control and laparotomy groups soon after the procedure (p < 0.05). PLF IL-6 levels in the pneumoperitoneum group tended to be lower than those in the laparotomy group. In conclusion, CO2 pneumoperitoneum might induce different responses between systemic and peritoneal cytokines soon after the procedure in a rat model of intraperitoneal sepsis.
Effect of Selective Denervation of the Rat Pancreas on Pancreatic Endocrine Function
Authors: Nilsson C. , Zoucas Evita , Lundquist I. , Ihse I.
Published: April 2003

The purpose of this study was to investigate the influence of selective denervation of the rat pancreas on hormone secretion and on peripheral insulin sensitivity. Thirteen rats, 7 denervated and 6 sham operated, received an intravenous glucose challenge for 30 min. The basal plasma levels of insulin, glucagon and glucose did not differ between the two groups. An augmented insulin response to glucose was detected in the denervated group, whereas the glucagon response was unaffected. Glucose tolerance was marginally improved. Twenty-four rats, 12 denervated and 12 sham operated, received a constant infusion of glucose, insulin, epinephrine and propranolol in order to inhibit the endogenous insulin release and thus evaluate insulin sensitivity. No significant change in insulin sensitivity could be detected during our experimental conditions. We conclude that selective denervation brings about an increased insulin response to glucose, probably by interrupting a catecholaminergic negative tone on the β-cell. The sympathectomized animals did not disclose any apparent changes in peripheral insulin sensitivity.
Mechanism of Hyporesponsiveness Caused by Donor-Specific Transfusion to Allogeneic Minor Antigens
Authors: Nomoto K. , Kanoh K. , Suzuki H. , Shimura T. , Kuwano H.
Published: April 2003

Donor-specific transfusion (DST) is one of the methods to prevent allograft rejection, presumably through induction of donor-specific nonresponsiveness in humans and animal models. In this study, we used a skin graft model in fully allogeneic (AKR into B6), H-2 class I-disparate (bm1 into B6), class II-disparate (bm12 into B6), minor-H-disparate (C3H/SW into B6) and whole MHC-disparate (B10.BR into B10) combinations to analyze the mechanisms of DST-induced immunomodulation from the view point of antigen disparity. Skin graft survival was prolonged by DST only in the combination of bm1 and B6 as already confirmed by many reports. In other combinations, skin graft survivals were not prolonged at all by DST but rather shortened. In a fully allogeneic combination between AKR and B6 in which I-E antigens or Mls-1 antigens are recognized by T-cell subsets with TCR Vβ11 or Vβ6, respectively, responses to stimulation by anti-Vβ11 and Vβ6 monoclonal antibodies were decreased by DST. Furthermore, the number of Vβ6+ T cells was decreased in the periphery probably due to peripheral clonal deletion. In such a condition, the mixed lymphocyte reactions of B6 to AKR were reduced to some extent, but were clearly detected. In addition, skin allografts from AKR were more rapidly rejected in B6 mice given AKR spleen cells. From these results, DST seems to induce nonresponsiveness to some antigens (I-E antigens, Mls antigens and bm1 antigens in this study), but not to others. Our study also indicated that DST alone, at least in the absence of other treatments, does not contribute to allograft tolerance in fully allogeneic combinations.
Pentoxifylline Contributes to the Hepatic Cytoprotective Process in Rats Undergoing Hepatic Ischemia and Reperfusion Injury
Authors: Aslan A. , Karagüzel G. , Çelik M. , Uysal N. , Yücel G. , Melikoglu M.
Published: April 2003

Aim: Considerable efforts have been made to find and/or eliminate the underyling causes of hepatic ischemia-reperfusion injury, but many points are still unclear. Pentoxifylline-related cytoprotection is one of these unclear points. Our study tests the effects of pentoxifylline on the hepatic cytoprotective process in an experimental model. Materials and Methods: The animals were divided into two groups: (1) placebo-pretreated rats and (2) pentoxifylline-pretreated rats. After pretreatment, all rats underwent the hepatic ischemia-reperfusion procedure which was performed by clamping the hepatoduodenal ligament. To evaluate the liver injury, serum levels of alanine transaminase (ALT) and aspartate transaminase (AST), and liver tissue levels of prostaglandin E2 (PGE2) were measured before ischemia, immediately after ischemia and immediately after reperfusion. Results: Before ischemia and immediately after ischemia, there were no significant differences between ALT and AST levels of groups 1 and 2 (p >0.05). However, at the end of reperfusion, ALT and AST levels of group 2 were significantly decreased when compared with group 1 (p < 0.05 and p < 0.01, respectively). Additionally, tissue levels of PGE2 that were obtained before ischemia, immediately after ischemia and immediately after reperfusion in group 2 were significantly higher than those of group 1 (p < 0.001). Conclusion: Pentoxifylline reduces reperfusion injury of the liver through significantly decreased transaminase levels, and contributes to hepatic cytoprotection by increasing tissue levels of PGE2 significantly. These effects reflect the role of tissue PGE2 in pentoxifylline-related hepatoprotection against ischemia-reperfusion injury of the liver.
Fas Receptor Is Upregulated in Livers from Non-Heart-Beating Donors
Authors: Schnurr C. , Glatzel U. , Tolba R. , Hirner A. , Minor T.
Published: April 2003

Cell injury in livers from non-heart-beating donors (NHBDs) is not only caused by necrosis, but it is increasingly being recognized that apoptotic transformation contributes to postischemic cell death. It remains unclear which pathways lead to apoptosis. We suggested that apoptosis in NHBD livers might be mediated by the Fas receptor. Therefore the aim of our study was the detection and quantification of the Fas receptor, Fas mRNA and apoptosis in NHBD livers. Livers of male Wistar rats were harvested either from heart-beating donors (control, n = 15) or 30 min after cardiac arrest from NHBDs (n = 15). All livers were stored in University of Wisconsin solution for 24 h at 4°C, and reperfused using a recirculating model with oxygenated Krebs-Henseleit buffer for 120 min at 37°C. Conventional signs of cell damage, such as enzyme release and bile production, showed an elevated nonspecific cell injury in NHBD livers. The immunohistochemical staining of Fas antigen expression revealed a 7% rate of Fas receptor-expressing hepatocytes in the control group, but a considerable increase up to 38% in the NHBD group. No Fas antigen expression was detected on sinusoidal endothelial cells. Real-time RT-PCR detected an approximately eightfold elevated concentration of Fas mRNA transcripts in NHBD livers. We conclude that upregulation of the Fas receptor on hepatocytes in NHBDs will prime these cells to eventually undergo apoptosis upon reperfusion in vivo. Therefore, therapeutic modulation of the Fas pathway must be considered as a new strategy in order to additionally protect NHBD livers which are otherwise prone to parenchymal apoptosis.
Behavioural Diversity among the Wild Chimpanzee Populations of Bossou and Neighbouring Areas, Guinea and Côte d’Ivoire, West Africa
Authors: Humle Tatyana , Matsuzawa Tetsuro
Published: April 2003

We present a preliminary report on the differences and similarities in material culture among four neighbouring chimpanzee (Pan troglodytes verus) communities. One of these communities includes Bossou, a long-term field site of wild chimpanzees, in Guinea, West Africa. We also conducted surveys of three new sites. Two of those surveyed areas, Seringbara in Guinea and Yealé in Côte d’Ivoire, are located less than 12 km away from Bossou in the Nimba Mountains region, which forms a natural boundary between Guinea and Côte d’Ivoire. The third, Diécké, is situated further south-west, closer to the border with Liberia. During the surveys, we gathered behavioural information about these neighbouring populations of chimpanzees. The differences, as well as similarities, in material culture were tabulated based on our findings. The three behavioural variants found so far involve differences in nut cracking behaviour with regard to the species of nut cracked. Some variation in materials used for nut cracking has also been recorded. However, we still need to establish whether these local variations can be explained by the demands of the physical and biotic environments in which the populations of chimpanzees live. If these alternative hypotheses can be excluded with continuing research at the study sites, these differences are likely to be cultural behaviours that are influenced by the social context and mode, i.e. horizontal, vertical or oblique, of transmission, by the social structure and organisation of each community and/or perhaps by some form of social norms prevalent within these communities.
A Biomechanical Study of the Long Bones in Platyrrhines
Authors: Llorens Laura , Casinos Adrià , Berge Christine , Majoral Muntsa , Jouffroy Françoise-Kyou
Published: April 2003

The long bones of 72 individuals of extant platyrrhines, belonging to 17 species (11 genera) were studied by regressions of length, diameters and curvature. Cross-sectional shapes at midshaft and axial and bending strength indicators were also calculated. Results show that forelimb bones scale faster than hindlimb bones, for both length and diameters. Curvature scales faster in the femur than in other bones. Strength indicators showed a high variability in the relative importance of axial and bending loadings. Results are consistent with field observations of locomotor behaviour, mainly as regards quadrupedalism versus suspensory locomotion.
Mice Genetic Immunization with Plasmid DNA Encoding a Secreted Form of HSV-1 gB Induces a Protective Immune Response against Herpes simplex Virus Type 1 Infection
Authors: Caselli E. , Grandi P. , Argnani R. , Balboni P.G. , Selvatici R. , Manservigi R.
Published: April 2003

Intramuscularly (i.m.) delivered plasmid DNA encoding a secreted form of glycoprotein B of herpes simplex virus type 1 (HSV-1 gB1s) was evaluated for the ability to elicit a protective immune response in Balb/c mice. Animals received three i.m. injections of a gB1s expression plasmid (pRP-RSV-gB1s) or of a wild-type transmembrane gB1 coding plasmid (pRP-RSV-gB1), while control mice were injected with the vector alone (pRP-RSV). A specific antibody response was observed in almost all immunized animals, and in most cases antibodies were also detected after 1 month in the absence of further vaccine boosts. Serum antibodies mostly displayed neutralizing activity against HSV-1. Glycoprotein B1s DNA immunization was also effective in protecting animals against the primary infection induced by a subsequent HSV-1 challenge and limited HSV-1 infection of sensitive ganglia.
121R Protein from the E3 Region of Bovine Adenovirus-3 Inhibits Cytolysis of Mouse Cells by Human Tumor Necrosis Factor
Authors: Zakhartchouk Alexender N. , Godson Dale L. , Babiuk Lorne A. , Tikoo Suresh K.
Published: April 2003

Based on the DNA sequence and known mRNA structures, the early region 3 (E3) of bovine adenovirus (BAV)-3 has the potential to encode four proteins. One of them (121R) is produced as a 14.5-kD protein throughout infection. Analysis of the 121R protein showed limited homology to a 14.7K protein of human adenovirus (HAV)-5. Interestingly, both anti-14.7K and anti-121R sera immunoprecipitated a 14.5-kD protein from cells infected with BAV-3. To determine if 121R is functionally related to 14.7K, we constructed a recombinant E3-deleted HAV-5 (AdKV121) expressing the BAV-3 E3 121R protein. Mouse C3HA cells infected with HAV-5 mutant dl 758 (deletion of 14.7K) were sensitive to TNF lysis. However, wild-type HAV-5- or recombinant AdKV121-infected cells were resistant to TNF-induced cytolysis. Our result show that the BAV-3 E3 121R protein is serologically and functionally related to the 14.7K protein encoded by the E3 region of HAV-5.
Vaccination against Hepatitis Delta Virus Infection: Studies in the Woodchuck (Marmota monax) Model
Authors: Fiedler Melanie , Roggendorf Michael
Published: April 2003

Hepatitis delta virus (HDV) superinfection of hepatitis B virus carriers causes severe liver disease and results in a high rate of chronicity. So far, neither sufficient therapy nor vaccines to prevent HBV carriers from superinfection are available. A good model to test vaccine candidates is the woodchuck chronically infected with the woodchuck hepatitis virus (WHV); the woodchuck can be superinfected with HDV and shows a course of infection similar to that of patients. Different strategies have been investigated to establish a protective vaccine against HDV superinfection. Both proteins of HDV (HDAg p24 and p27), which differ only in the C-terminal amino acid sequence, have been used as vaccine candidates. Synthetic peptides derived from B cell epitopes of HDAg and HDAg p24 expressed in Escherichia coli, yeast, or baculovirus have been used to immunize woodchucks. The protein immunization induced a specific antibody response, however, no protection from HDV superinfection was achieved. Vaccinations with vaccinia virus expressing HDAg p24 or p27 and DNA immunization with vectors expressing p24 were also not able to induce a protective immune response, but seemed to modulate the course of HDV superinfection. Thus, new strategies to develop a vaccine to prevent HDV superinfection are needed.
Interleukin-4 Is Needed for the Infection of Monocytes by Human Cytomegalovirus
Authors: Kitajima Hiromoto , Okubo Yasumitu , Honda Junichi , Yonemitsu Junko , Yoshida Nobukuni , Fumimori Takehide , Oizumi Kotaro
Published: April 2003

Objective: We studied the ability of human cytomegalovirus (HCMV) to infect peripheral blood mononuclear cells (PBMC) pretreated with or without Th2-cytokine interleukin-4 (IL-4) in vitro. Methods: Adherent cells and nonadherent cells were obtained from PBMC. We inoculated these cells with HCMV at concentrations ranging from 0 to 10 ng/ml of IL-4. Immediate-early antigen-1 (IE-1) and glycoprotein H (gH) mRNAs were detected using the reverse-transcription polymerase chain reaction. Results: IE-1 and gH mRNAs could be detected in monocytes pretreated with IL-4. In contrast, no IE-1 mRNA was detected in monocytes pretreated without IL-4. We tested whether higher infectious titers could result in the infection of monocytes whether or not they were pretreated with IL-4. However, no IE-1 mRNA was detected in the monocytes not pretreated with IL-4. To elucidate how HCMV-infected monocytes affect lung tissue, human embryonic lung fibroblasts MRC-5 were cocultured with HCMV-infected monocytes. The cytopathic effects of HCMV were observed microscopically and was confirmed by direct immunoperoxidase staining with a human monoclonal antibody against the HCMV IE-1. Conclusion: Our data strongly suggest that the ability of HCMV to infect monocytes may correlate with the presence of IL-4.
Amino Acid Substitution Analyses of the DNA Contact Region, Two Amphipathic α-Helices and a Recognition-Helix-Like Helix outside the Dimeric β-Barrel of Epstein-Barr Virus Nuclear Antigen 1
Authors: Fujita Tomomichi , Ikeda Masato , Kusano Shuichi , Yamazaki Makoto , Ito Sayuri , Obayashi Maya , Yanagi Kazuo
Published: April 2003

Objectives and Methods: Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1), which is essential for EBV latency, homodimerizes and binds to the EBV replication origin, oriP. We analyzed the dimerization/DNA-binding domain of EBNA-1 by random and site-directed amino acid substitution. Results: Random point mutations that resulted in reduced DNA binding clustered in the DNA contact region (a.a. 461–473) and at or near the termini of α-helix II (514–527). Three substitutions of Gly in the DNA contact region each greatly reduced binding to a single binding site oligonucleotide. Substitutions at and near the termini of α-helix II diminished DNA binding. A helix-deforming substitution in α-helix I (477–489) blocked DNA binding. A helix-deforming substitution in α-helix III (568–582) abolished dimerization and DNA binding. Similarities in surface electrostatic properties and conserved amino acids were found between α-helix II and recognition helices of papillomavirus E2 proteins. Conclusions: The basic DNA contact region is crucial for the specific interaction of EBNA-1 with a single binding site. α-Helix I477 is indispensable for oriP binding, and α-helix III568 contributes to the homodimeric structure of EBNA-1. α-Helix II514 contributes to oriP binding, perhaps changing its alignment with DNA.
Genetic Polymorphism of the MxA Gene Promoter and Interferon Responsiveness of Hepatitis C Patients: Revisited by Analyzing Two SNP Sites (–123 and –88) in vivo and in vitro
Authors: Hijikata Minako , Mishiro Shunji , Miyamoto Chikara , Furuichi Yasuhiro , Hashimoto Michie , Ohta Yasuhiko
Published: April 2003

We have previously reported a single nucleotide polymorphism (SNP) at nucleotide (nt) position –88 (G or T) within an interferon-stimulated response element-like sequence in the promoter region of the MxA gene, which correlated with responsiveness of hepatitis C patients to interferon. Upstream of it, we then identified another SNP (C or A at nt –123) and investigated whether this SNP also correlates with interferon responsiveness. The two SNPs showed a high linkage to each other: all the individuals having G at –88 had C at –123, and 73% of those having T at –88 had A at –123. As was expected from this observation, the SNP at –123 also exhibited a correlation with interferon responsiveness (C/C homozygotes were more frequent among nonresponders than among responders: 65% of 107 vs. 40% of 52, p = 0.0028). These in vivo data from patients were further supported by results from in vitro experiments. The MxA promoter sequence with A at –123 and T at –88 showed about 4-fold higher activity of upregulating the downstream reporter gene than that with C at –123 and G at –88, in a luciferase reporter assay.
Liver Transplantation-Associated de novo Hepatitis B Virus Infection: Application of Molecular Evolutionary Analysis
Authors: Sugauchi Fuminaka , Orito Etsuro , Ohno Tomoyoshi , Kato Hideaki , Suzuki Tatsuya , Hashimoto Takashi , Manabe Tadao , Ueda Ryuzo , Mizokami Masashi
Published: April 2003

Objective: De novo hepatitis B virus (HBV) infection after liver transplantation has recently been reported to be associated with donors without serum hepatitis B surface antigen (HbsAg) but with hepatitis B core antigen (anti-HBc). We elucidate the source of de novo HBV infection after liver transplantation by molecular evolutionary analysis. Methods: The serum sample was obtained from a recipient who underwent living related liver transplantation. He was negative for all HBV-related serum markers before the transplantation. The recipient became seropositive for HBsAg at 6 months after transplantation. The liver tissue was obtained from a donor who was seronegative for HBsAg, but positive for anti-HBs and anti-HBc. Results: HBV DNA was detected from the serum and liver tissue in a recipient and donor, respectively. A total of 5 clones each of small-S gene of HBV from the donor and recipient were sequenced. A phylogenetic tree analysis based on small-S gene revealed that all isolates derived from the recipient and donor were clustered together within a close range of evolutionary distances. These results indicated that HBV was transmitted by the liver graft from the donor. Conclusions: Molecular evolutionary analysis can be adopted for the study of the transmission route of viral infection via organ transplantation.
Analysis of Background Factors Influencing Long-Term Prognosis of Patients with Chronic Hepatitis C Treated with Interferon
Authors: Yoneyama Keiichiro , Yamaguchi Mayumi , Kiuchi Yuji , Morizane Toshio , Shibata Minoru , Mitamura Keiji
Published: April 2003

Objective: Interferon (IFN) therapy has been used as antiviral therapy for chronic hepatitis C (CH-C); however, complete response to the therapy is observed in only about 30% of patients in Japan. Background factors involved in the responsiveness to IFN therapy, and progression to liver cirrhosis (LC) and hepatocellular carcinoma (HCC) after IFN therapy have not yet been sufficiently investigated. Methods: One hundred twenty-one patients with CH-C who received IFN therapy at Showa University Hospital between 1984 and 1999 were analyzed. Results: At 6 months after the termination of IFN therapy, 53 patients achieved a complete response, 11 patients incomplete response, and 57 patients no response. During a mean follow-up of 52.7 months, 12 patients progressed to LC, and 10 patients developed HCC. Multivariate analysis showed that significant independent factors involved in progression to LC were platelet count and the efficacy of IFN therapy. The significant independent factor involved in the development of HCC was platelet count. The factor involved in the therapeutic effect at 6 months after the termination of IFN administration was the serum hepatitis C virus (HCV) RNA levels before IFN therapy. Conclusion: Patients with high HCV RNA levels and low platelet counts should be considered to be at high risk of progressing to LC and developing of HCC and should be carefully followed after IFN therapy using ultrasonography, CT scan and MRI.
Clinical and Subclinical Reactivation of Genital Herpes Virus
Authors: Wolff Manfred H. , Schmitt Judith , Rahaus Markus , Dudda Hans , Hatzmann Wolfgang
Published: April 2003

Reactivations of herpes simplex virus (HSV) either symptomatically (recrudescence) or without symptoms (recurrence) are well documented. As an asymptomatic reactivation may contribute to transmitting HSV to potential acceptors the frequency of reactivations should be evaluated. In order to evaluate the frequency of HSV-2 reactivation 173 genital swabs of a group of women chosen at random were analyzed by nested PCR. 34 (19.6%) showed clinical evidence of a herpes infection, 77 (44.5%) had no symptoms at all and 62 (35.8%) had other symptoms. In 26 (15%) HSV-DNA was detected. 11 (38.4%) could be characterized as asymptomatic reactivations. Typing of the HSV-positive swabs resulted in 11 HSV-2 and 10 HSV-1 strains. Additionally 18 HSV-positive swabs of the oral cavity resulted in 15 (83.2%) HSV-1 and 3 (16.4%) HSV-2 strains. The results of typing indicate a change of HSV-1 and HSV-2 epidemiology.
Quality of Life after Surgical Therapy of Small Bowel Stenosis in Crohn’s Disease
Authors: Broering D.C. , Eisenberger C.F. , Koch A. , Bloechle C. , Knoefel W.T. , Izbicki J.R.
Published: April 2003

Background: Improvement in quality of life is one of the important determinants in the treatment of Crohn’s disease. Since there is no cure with radical resection of inflamed bowel, strictureplasty has become a useful surgical technique in the treatment of small bowel obstruction. The scope of this study was to define the results of strictureplasty and resection in terms of quality of life, surgical recurrence and postoperative complications. Methods: The charts of 67 patients with Crohn’s disease of the small bowel were analyzed retrospectively. Patients were treated either by strictureplasty (group A) or resection (group B). Quality of life was evaluated in follow-up examinations using the Inflammatory Bowel Disease Questionnaire (IBDQ). Results: Postoperative morbidity was 14.8% after strictureplasty and 17% after resection (p = 0.8). 50% of the patients treated by strictureplasty and 37% treated by resection developed recurrent disease (p = 0.40). Quality-of-life measurement revealed no significant difference between patients treated by strictureplasty or resection. Conclusion: Results after strictureplasty are comparable to those after resection in terms of complications, recurrence and quality of life in the treatment of small bowel strictures in Crohn’s disease. In the long run there might be an advantage for strictureplasty because it prevents complications caused by resectional therapy such as short bowel syndrome.