14-3-3 proteins and zeta isoform containing neurofibrillary tangles in patients with Alzheimer’s disease

Immunolocalization of 14-3-3 proteins in Alzheimers disease (AD) brains was investigated using isoform-specific antibodies. Weak granular immunoreactivity of 14-3-3 proteins was found in neuronal cytoplasm in control subjects and AD brains. Both intracellular and extracellular neurofibrillary tangles (NFTs), as well as neuropil thread-like structures, were immunopositive for 14-3-3 proteins. This was corroborated by triple-fluorolabeling method visualizing paired helical filament (PHF) tau and 14-3-3 epitopes in relation to fibrillary state detected by thiazin red. Pretangle neurons (positive for PHF-tau without fibrillary structure detected by thiazin red) only contained fine granular immunoreactivity (IR) of 14-3-3, which was similarly found in unaffected neurons. Granular cytoplasmic IR of 14-3-3 proteins in pretangle neurons was not colocalized to granular tau-like IR, which suggests that participation of 14-3-3 proteins in NFT formation was restricted to its later stages. Its zeta isoform was most prominent in these NFTs, suggesting that this isoform is a major component involved in the formation of NFTs. In contrast, IR of epsilon isoform was found in the neuropil of the hippocampus and that of sigma isoform was localized to granule cells of the dentate gyrus in AD brains, as seen in the age-matched controls. Expression of 14-3-3 proteins were found to be highly variable and dependent on their isoforms, regions and cell types. Molecular, as well as topographical, dissection of 14-3-3 proteins will provide us with an improved understanding of this molecule in normal and pathological conditions.     

C-erbB-2、PCNA、ER、PR在乳腺癌中的表达及临床意义

目的探讨分析乳腺癌组织中C—erbB-2、增殖细胞核抗原（PCNA）及雌、孕激素受体（ER、PR）的表达及其意义。方法采用免疫组化法检测269例乳腺癌组织中C—erbB-2、PCNA、ER、PR的表达情况。结果乳腺癌组织中C—erbB-2、PCNA、ER、PR的阳性表达率分别为69．52％、78．81％、51．67％和59．48％。C—erbB-2表达与乳腺癌患者腋淋巴结转移及肿瘤的浸润性相关（P〈0．01）;PCNA表达仅与腋淋巴结转移相关（P〈0．01）,而与肿瘤的浸润性无关（P〉0．05）;ER、PR表达呈正相关（r=0．522,P=0．000）,C—erbB-2、PCNA表达呈正相关（r=0．182,P=0．003）。结论联合检测乳腺癌组织中C—erbB-2、PCNA、ER、PR的表达对于乳腺癌的治疗具有指导意义,也是判断预后的重要指标。     

Immune tolerance induction using a factor VIII/von Willebrand factor concentrate (BIOSTATE®), with or without immunosuppression,in Australian paediatric severe haemophilia A patients with high titre inhibitors: A multicentre,retrospective study

Introduction

It has been postulated that factor VIII (FVIII) products containing von Willebrand factor (VWF) may improve immune tolerance induction (ITI) success rate in patients with haemophilia A and poor prognostic factors.

Materials and methods

We conducted a retrospective cohort analysis of a FVIII/VWF concentrate (BIOSTATE®) for ITI in paediatric patients with severe haemophilia A (SHA) and inhibitors, from January 2003 to December 2011 at 3 paediatric-only Haemophilia Treatment Centres in Australia. Response to ITI was assessed at or before 33 months and at completion of ITI. Fifteen male patients with SHA were included in the analysis.

Results

BIOSTATE was used for primary ITI in 8 patients (2 years, range 1.1–11.5 years) and for salvage ITI in 7 patients (9.9 years, range 1.1–15.4). At the end of the observation period there were 11 patients who achieved a complete response with BIOSTATE after a median duration of 21 months (range 5–85 months); a partial response was achieved in 2 patients in whom ITI is ongoing. Therefore, the overall response rate was 86.6%. Two patients were deemed treatment failures: one due to non-compliance after 18 months of ITI and another in whom a partial response had not been achieved after 22 months of ITI.

Conclusion

BIOSTATE was well-tolerated and effective when used for primary or salvage ITI in this cohort of paediatric patients with SHA and a high-level inhibitor.     

Long-term,open-label,safety study of once-daily ropinirole extended/prolonged release in early and advanced Parkinson's disease

Long-term safety of once-daily ropinirole extended/prolonged release (ropinirole XL/PR) was evaluated in subjects with early and advanced Parkinson's disease (PD) in this study, 101468/248. Subjects (n = 419) who completed one of three prior studies evaluating ropinirole XL/PR for the treatment of PD were enrolled in this open-label, multicenter, extension study, and were to be followed for up to 73 months. Ropinirole XL/PR was titrated/continued, and adjusted as appropriate during the maintenance phase (maximum 24 mg/d). Levodopa (L-dopa) and other nondopamine agonist PD medications were permitted. Safety outcomes that were investigated included frequency of adverse events (AEs). Subjects’ preference regarding once daily versus three times daily study medication regimens was also investigated in a subset of the study population. The median duration of ropinirole XL/PR exposure was 1275 d. Most subjects (87%) reported at least one AE, with the most common (≥ 10%) AEs being, back pain (14%), hallucinations (13%), somnolence (11%) and peripheral edema (11%). Twenty-five percent of subjects discontinued the study prematurely due to an AE during the treatment period. Long-term treatment with ropinirole XL/PR was not associated with any new or unexpected safety concerns in patients with early and advanced PD, and a majority of subjects preferred the once-daily dosing regimen.     

Hepatoprotective effects of Artemisiae Capillaris Herba and Picrorrhiza Rhizoma combinations on carbon tetrachloride–induced subacute liver damage in rats

The hepatoprotective properties of Artemisiae Capillaris Herba (AC) and Picrorrhiza Rhizoma (PR) are well known. The aim of this study was to determine the optimal composition of AC and PR mixtures for better complimentary or alternative regimens in reducing the level of hepatic fibrosis. Ten weeks of carbon tetrachloride injections caused subacute hepatic damage, manifested as significantly less body weight gain and hepatic protein content, and a higher liver weight, serum aspartate aminotransferase and alanine aminotransferase levels, hepatic malondialdehyde (an index for lipid peroxidation), and hydroxyproline (an index for collagen synthesis) concentrations. The carbon tetrachloride–induced toxic effects were inhibited by 11 different AC/PR mixtures as well as the single AC or PR treatment. More favorable effects were detected in all mixed-formulation groups compared with the AC or PR single formulations. Moreover, the AC/PR 2:1 formulation showed the most favorable hepatoprotective activity. The AC and PR mixtures showed good synergic hepatoprotective activity that was attributed to increasing free-radical scavenging ability. Among the 11 types of mixed formula tested in this study, the AC/PR 2:1 formulation had the most impressive synergic effects on inhibiting the subacute hepatic damage induced by carbon tetrachloride in rats and showed more favorable effects than with an equal dose of silymarin.     

卵巢上皮性癌ER、PR和Ki67表达及其临床意义分析

[目的]研究ER、PR和Ki67在卵巢上皮性癌中的表达及其临床意义。[方法]用单克隆抗体、免疫组化技术测定74例原发性卵巢上皮性癌患者中ER、PR和Ki67的表达。[结果]ER、PR、Ki67的阳性表达率分别是59．5％、60．8％、74_3％，PR表达与临床分期相关。多因素分析显示PR表达、临床分期是独立的预后因素。[结论]在卵巢上皮性癌中，PR表达、临床分期具有独立的判断患者预后的价值。     

Once-monthly radiotherapy for the palliation of pelvic gynecological malignancy

Twenty-seven patients with advanced pelvic gynecological malignancies were treated using a once-monthly fractionation scheme of 10 Gy to a total dose of 30 Gy to the whole pelvis. This course was well tolerated and provided effective palliation with a minimum of hospitalization. The results obtained suggest this course merits consideration for the palliation of other pelvic malignancies.