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  • 1
    ISSN: 1365-2826
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Accumulating evidence suggests that both oxytocin and arginine vasopressin (AVP) are vital components in the regulation of body fluid balance. However, the physiological role of oxytocin and possible cooperative interactions between oxytocin and AVP in sodium balance remain obscure, even though recent studies using oxytocin knockout (OTKO) mice suggested that oxytocin may contribute to the regulation of salt appetite. In the present study, we examined the effects of salt loading (drinking 2% NaCl for 5 days) on the expression of the AVP gene in the paraventricular (PVN) and supraoptic nuclei (SON) of wild-type, OTKO and heterozygous littermates using in situ hybridization histochemistry. In addition, the effects of salt loading on the expression of the oxytocin gene were also examined in wild-type and heterozygous mice. Under the non salt-loaded condition, the levels of AVP mRNA in the PVN and SON of OTKO mice were significantly decreased compared to those in wild-type mice. Nevertheless, the up-regulation of the expression of the AVP gene in response to salt loading was preserved in OTKO mice. The degree of the up-regulation in OTKO mice tended to be greater compared to those in wild-type mice, suggesting compensatory up-regulation of the expression of the AVP gene in OTKO mice after salt loading. The basal levels of oxytocin mRNA in the PVN and SON of heterozygous mice were significantly lower than those in wild-type mice. Salt loading caused an increase of oxytocin mRNA levels in the PVN and SON of both wild-type and heterozygous mice. The ratios of increase of oxytocin mRNA levels were very similar between wild-type and heterozygous mice, suggesting that the single remaining oxytocin gene in heterozygous mice responds normally to an osmotic cue. Finally, salt loading tended to increase the serum concentration of sodium regardless of genotype, and there were no genotype differences in both the control and salt-loaded groups. These results suggest ways in which oxytocin may play a cooperative role together with AVP in the regulation of sodium balance.
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neuroendocrinology 16 (2004), S. 0 
    ISSN: 1365-2826
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The physiological actions of angiotensin II in the supraoptic (SON) and paraventricular nuclei have been widely demonstrated, including the modulation of firing rate and release of arginine vasopressin and oxytocin. Here, we investigated whether angiotensin II modulates synaptic inputs into the SON. To do this, we measured spontaneous excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) from rat SON neurones in thin slice preparations using the whole-cell patch-clamp technique. Angiotensin II reversibly increased the frequency of spontaneous EPSCs in a dose-related manner without affecting the amplitude, indicating that angiotensin II potentiated EPSCs via a presynaptic mechanism. Angiotensin II-induced potentiation of EPSCs was unaffected in the presence of tetrodotoxin. On the other hand, angiotensin II did not cause significant effects on IPSCs. The potentiation of EPSCs by angiotensin II was potently suppressed by previous exposure to the angiotensin type 1 (AT1) receptor antagonist, losartan. Our results suggest that angiotensin II potentiates the excitatory synaptic inputs into SON neurones, via the AT1 receptors.
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  • 3
    ISSN: 1365-2516
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary.   We report a case of haemophilia A with a high responding inhibitor of factor VIII (FVIII) who had a serious retroperitoneal haematoma caused by penetration of a duodenal ulcer. Inhibitor-bypassing therapy was commenced immediately on admission. On the 17th day of treatment with activated prothrombin complex concentrate (APCC; FEIBA®), re-bleeding occurred and thrombelastography (TEG) demonstrated resistance to therapy. Treatment was changed to recombinant activated factor VII (rFVIIa; NovoSeven®) and resulted in clinical improvement together with an improvement in TEG parameters. On the 10th day of continuous infusion with NovoSeven®, however, TEG again showed resistance to therapy. FEIBA® infusions were re-introduced and TEG results remained satisfactory for 7 days. On day 34, however, further retroperitoneal bleeding was evident and a decline in the haemostatic efficiency of FEIBA® was recorded by TEG. NovoSeven® was again successfully administered for 7 days. There were no laboratory findings to indicate disseminated intravascular coagulation (DIC), hypercoagulability or abnormal fibrinolysis. The plasma-based clotting tests did not show any additional prolongation on the occasions when the TEG demonstrated unresponsiveness to FEIBA® or NovoSeven®. These findings suggested that some component of whole blood, other than plasma might have governed the TEG data. The long-term use of APCC such as FEIBA® or rFVIIa, requires careful monitoring in terms of FVIII inhibitor bypassing activity as well as the tendency to DIC.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1365-2516
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary.  We report here the efficacy of factor VIII (FVIII) infusions in two haemophiliacs with inhibitors using clot waveform analysis on the MDA® II system, which was possible to detect very low levels of FVIII activity 〈 1.0 U dL−1. In the presence of type 1 inhibitors at the level of 6.2 (patient 1) and 14.4 (patient 2) Bethesda Units mL−1, 3.2 and 6.5 U dL−1 of FVIII:C remained 30 min after the infusion of FVIII (100 U kg−1), respectively. Moreover, 0.9 U dL−1 of FVIII:C remained 24 h after infusion in patient 2. In both cases, these changes were reflected by qualitative improvement in the aPTT clot waveform and quantitative changes in the minimum value of the second derivative of the aPTT waveform (Min2) that reflects clot acceleration. These results suggest that FVIII infusion may be continued with clinical benefit in some haemophiliacs with high responding inhibitors. Furthermore, the haemostatic response may be monitored accurately and efficiently by clot waveform analysis.
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Clinical and experimental dermatology 27 (2002), S. 0 
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary Werner syndrome (WS) is caused by mutations in the gene encoding RecQ type DNA helicase (WRN). We report a 53-year-old Japanese male with WS who initially presented with skin ulcers on the feet and the left elbow. The patient had a high-pitched voice, hoarseness, a characteristic bird-like facial appearance with a beak-shaped nose, canities and juvenile cataracts. Immunoblot analysis using a monoclonal antibody directed against the WS gene product DNA helicase revealed that the patient's leucocytes lacked this particular molecule, confirming the diagnosis of WS. This new immunoblot system therefore enables the diagnosis of WS to be made without the need to undertake more complex mutational analysis.
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  • 6
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: To establish whether MIB-1 and p53 staining are useful for differentiating pilocytic astrocytomas and astrocytomas from anaplastic astrocytomas and glioblastomas. This study was restricted to children and young adults under 30 years of age because of the differences in p53 mutations between paediatric and adult astrocytomas.〈section xml:id="abs1-2"〉〈title type="main"〉Methods and resultsForty-five astrocytic tumours, including 18 pilocytic astrocytomas, 14 astrocytomas, four anaplastic astrocytomas and nine glioblastomas, from 45 children and young adults, between 1 and 29 years (mean 11 years) of age, were examined pathologically, and sections from paraffin-embedded blocks were used for MIB-1 and p53 immunostaining. The MIB-1 labelling index and the frequency and intensity of p53 staining in both the pilocytic astrocytoma and the astrocytoma group were significantly lower than in the anaplastic astrocytoma plus glioblastoma group (P 〈 0.001). In 11.1% (two of 18) of pilocytic astrocytomas and 42.9% (six of 14) of astrocytomas, immunoreactivity of either MIB-1 or p53 staining was of almost the same intensity as that of anaplastic astrocytomas and glioblastomas. However, in these cases, results using both MIB-1 and p53 stain differed from those for anaplastic astrocytomas and glioblastomas.〈section xml:id="abs1-3"〉〈title type="main"〉ConclusionsMIB-1 and p53 co-staining is very useful for differentiating pilocytic astrocytomas and astrocytomas from anaplastic astrocytomas and glioblastomas. However, MIB-1 or p53 staining alone cannot differentiate pilocytic astrocytomas and astrocytomas from anaplastic astrocytomas and glioblastomas.
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Histopathology 37 (2000), S. 0 
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aims:  The aim of this study was to elucidate possible clinicopathological differences between diffusely infiltrating gastric carcinoma of ‘pure type’ (poorly differentiated carcinoma without any glandular component) and ‘mixed type’ (coexistence of poorly differentiated carcinoma and intramucosal glandular component).Methods and results:  The clinicopathological features and immunohistochemical expression of p53 and intercellular adhesion molecules (E-cadherin and α-, β- and γ-catenins) were compared between the patients with pure (n=59) and mixed (n=56) types of diffusely infiltrating gastric carcinoma. Intestinal metaplasia (P 〈 0.01), prominent lymphatic permeation (P 〈 0.001) and lymph node metastasis (P 〈 0.05) were more frequently observed in mixed type than in pure type, while survival probability did not differ between the two groups. The frequency of p53 over-expression was higher in mixed type (56%) than in pure-type (19%) (P 〈 0.001). In mixed type, p53 expression was not different between glandular and poorly differentiated components. By contrast, the expression of adhesion molecules was more frequently preserved in glandular components than in poorly differentiated components.Conclusions:  These two subtypes seem to be different in nature and biological behaviour. The preservation of adhesion molecules in mixed type may be associated with higher incidence of lymphatic permeation and lymph node metastasis.
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  • 9
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background : In Helicobacter pylori infection, the effect of short-term triple therapy with proton pump inhibitor plus two antibiotics on gastric ulcer healing is not well known.Aim : To compare 1-week triple therapy with 8-week proton pump inhibitor therapy on gastric ulcer healing in infected patients.Patients and methods : We randomly assigned 120 patients with H. pylori and gastric ulcers to proton pump inhibitor plus amoxicillin and clarithromycin for 1 week (n = 61) or proton pump inhibitor alone for 8 weeks (n = 59), with endoscopic assessment of ulcer healing 8 weeks after the start of treatment.Results : Triple therapy eradicated H. pylori in 51 patients [intention-to-treat, 84%; 95% confidence interval (CI), 75–93%]. At 8 weeks, gastric ulcers were healed in 30 patients given triple therapy (49%; 95% CI, 37–62%) and in 49 patients given proton pump inhibitor (83%; 95% CI, 73–93%, P 〈 0.001). Healing rates in the triple therapy and proton pump inhibitor-only groups were 89% and 100%, respectively, for ulcers of 〈 1.0 cm in diameter, 54% and 77% for ulcers of 1.0 to 〈 1.5 cm in diameter, and 5% and 77% (P 〈 0.001) for ulcers of ≥ 1.5 cm in diameter.Conclusions : One-week triple therapy healed most ulcers of 〈 1.0 cm, but not ulcers of ≥ 1.5 cm. Short-term therapy is effective for gastric ulcers of 〈 1.0 cm, but, for larger ulcers, follow-up therapy to suppress acid is needed.
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  • 10
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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