3,4-二氯苯丙烯酰另丁胺对大鼠脑缺血-再灌注损伤的影响

目的：研究新的桂皮酰胺类衍生物,３－４二氯苯丙烯酰另丁胺（ＡＥＤ８８０１）对大鼠脑缺血／再灌注损伤的影响。方法：采用Ｐｕｌｓｉｎｅｌｌｉ四血管阻断大鼠脑缺血／再灌注模型,观察了ＡＥＤ８８０１对脑组织中水含量、氨基到含量、６－ｋｅｔｏ－ＰＧＦ１α和ＴＸＢ２含量,以及二者之比值的影响。结果：一ＡＥＤ８８０１能够降低脑缺血／再灌注大鼠所引起的脑水含量增加。二采用氨基酸自动分析仪进行检测,发现脑缺血／再灌     

猪脑钠素及其类似物的合成

以固相多肽合成方法合成了猪的二十六肽脑钠素(BNP)和它的一个类似物(Mpr⁴,D-Ala^6,13)-BNP(4-24)-NH₂,保护肽用HF裂解除去保护基、在碱性条件下空气氧化形成二硫桥后,粗产物经凝胶过滤和高效液相色谱分离纯化,均有与天然脑钠素相同的活性。合成肽相对于树脂初始取代量的产率分别为9.56%和11.03%。     

Breast cancer risk in relation to urinary and serum biomarkers of phytoestrogen exposure in the European Prospective into Cancer-Norfolk cohort study

Introduction

Phytoestrogens are a group of compounds found in plants that structurally resemble the hormone oestradiol, and thus have the potential to act as oestrogen agonists or antagonists. Their potential effects may alter the risk of breast cancer, but only a limited range of phytoestrogens has been examined in prospective cohort studies.

Methods

Serum and urine samples from 237 incident breast cancer cases and 952 control individuals (aged 45 to 75 years) in the European Prospective into Cancer-Norfolk cohort were analysed for seven phytoestrogens (daidzein, enterodiol, enterolactone, genistein, glycitein, o-desmethylangolensin, and equol) using liquid chromatography/mass spectrometry. Data on participants' diet, demographics, anthropometrics, and medical history were collected upon recruitment. All models were adjusted for weight, fat and energy intake, family history of breast cancer, social class, analytical batch, and factors related to oestrogen exposure.

Results

Urinary or serum phytoestrogens were not associated with protection from breast cancer in the European Prospective into Cancer-Norfolk cohort. Breast cancer risk was marginally increased with higher levels of total urinary isoflavones (odds ratio = 1.08 (95% confidence interval = 1.00 to 1.16), P = 0.055); among those with oestrogen receptor-positive tumours, the risk of breast cancer was increased with higher levels of urinary equol (odds ratio = 1.07 (95% confidence interval = 1.01 to 1.12), P = 0.013).

Conclusion

There was limited evidence of an association between phytoestrogen biomarkers and breast cancer risk in the present study. There was no indication of decreased likelihood of breast cancer with higher levels of phytoestrogen biomarkers, but the observation that some phytoestrogen biomarkers may be associated with greater risk of breast cancer warrants further study with greater statistical power.     

Variable size computer-aided detection prompts and mammography film reader decisions

Introduction

The purpose of the present study was to investigate the effect of computer-aided detection (CAD) prompts on reader behaviour in a large sample of breast screening mammograms by analysing the relationship of the presence and size of prompts to the recall decision.

Methods

Local research ethics committee approval was obtained; informed consent was not required. Mammograms were obtained from women attending routine mammography at two breast screening centres in 1996. Films, previously double read, were re-read by a different reader using CAD. The study material included 315 cancer cases comprising all screen-detected cancer cases, all subsequent interval cancers and 861 normal cases randomly selected from 10,267 cases. Ground truth data were used to assess the efficacy of CAD prompting. Associations between prompt attributes and tumour features or reader recall decisions were assessed by chi-squared tests.

Results

There was a highly significant relationship between prompting and a decision to recall for cancer cases and for a random sample of normal cases (P < 0.001). Sixty-four per cent of all cases contained at least one CAD prompt. In cancer cases, larger prompts were more likely to be recalled (P = 0.02) for masses but there was no such association for calcifications (P = 0.9). In a random sample of 861 normal cases, larger prompts were more likely to be recalled (P = 0.02) for both mass and calcification prompts. Significant associations were observed with prompting and breast density (p = 0.009) for cancer cases but not for normal cases (P = 0.05).

Conclusions

For both normal cases and cancer cases, prompted mammograms were more likely to be recalled and the prompt size was also associated with a recall decision.     

A monokine regulates colony-stimulating activity production by vascular endothelial cells

Human umbilical vein endothelial cells were cultured in supernatants of peripheral blood monocytes that had been cultured for 3 days with and without lactoferrin. Colony-stimulating activity (CSA) was measured in supernatants of the endothelial cell cultures and appropriate control cultures using normal, T-lymphocyte-depleted, phagocyte-depleted, low- density bone marrow cells in colony growth (CFU-GM) assays. Monocyte- conditioned medium contained a nondialyzable, heat labile factor that enhanced 4-15--fold the production of CSA by endothelial cells. The addition of lactoferrin to monocyte cultures reduced the activity of this monokine by 69%. Lactoferrin did not inhibit CSA production by monokine-stimulated endothelial cells. Therefore, vascular endothelial cells are potent sources of CSA, the production of CSA by these cells is regulated by a stimulatory monokine, and the production and/or release of the monokine is inhibited by lactoferrin, a neutrophil- derived putative feedback inhibitor of granulopoiesis. Inasmuch as a similar monokine is known to stimulate CSA production by fibroblasts and T lymphocytes, we suggest that mononuclear phagocytes play a pivotal role in the regulation of granulopoiesis by recruiting a variety of cell types to produce CSA.     

Phrenic motor unit recruitment during ventilatory and non-ventilatory behaviors

Phrenic motoneurons are located in the cervical spinal cord and innervate the diaphragm muscle, the main inspiratory muscle in mammals. Similar to other skeletal muscles, phrenic motoneurons and diaphragm muscle fibers form motor units which are the final element of neuromotor control. In addition to their role in sustaining ventilation, phrenic motor units are active in other non-ventilatory behaviors important for airway clearance such as coughing or sneezing. Diaphragm muscle fibers comprise all fiber types and are commonly classified based on expression of contractile proteins including myosin heavy chain isoforms. Although there are differences in contractile and fatigue properties across motor units, there is a matching of properties for the motor neuron and muscle fibers within a motor unit. Motor units are generally recruited in order such that fatigue-resistant motor units are recruited earlier and more often than more fatigable motor units. Thus, in sustaining ventilation, fatigue-resistant motor units are likely required. Based on a series of studies in cats, hamsters and rats, an orderly model of motor unit recruitment was proposed that takes into consideration the maximum forces generated by single type-identified diaphragm muscle fibers as well as the proportion of the different motor unit types. Using this model, eupnea can be accomplished by activation of only slow-twitch diaphragm motor units and only a subset of fast-twitch, fatigue-resistant units. Activation of fast-twitch fatigable motor units only becomes necessary when accomplishing tasks that require greater force generation by the diaphragm muscle, e.g., sneezing and coughing.     

Obtaining clinical writing informed consent versus using client disguise and recommendations for practice

Clinical writing about psychotherapy clients has long been a part of didactic texts and research articles because it allows new treatments and interventions to be presented in an effective and memorable way. The main ways that clinicians write about their clients include obtaining informed consent, using client disguise, or creating case composites. Although many clinicians use a combination of all three approaches, this article specifically addresses the implications of using clinical writing informed consent. The present article begins with a brief history of clinical writing and an examination of the relevant standards in the current APA Ethics Code and the Health Insurance Portability and Accountability Act; this is followed by a discussion of the benefits of engaging in the clinical writing informed consent process. Subsequently, the limitations of using clinical writing informed consent are explored, including the potentially negative impact on the therapeutic alliance and the client's progress. The article concludes that clinicians should be cautious when deciding to engage in clinical writing informed consent. Recommendations in the form of a checklist are provided to help clinicians identify when it is most appropriate to use client disguise or case composites, and how to do so, as well as when it is appropriate to engage in clinical writing informed consent. Future directions are considered.     

Visually assessed breast density, breast cancer risk and the importance of the craniocaudal view

Introduction

Mammographic density is known to be a strong risk factor for breast cancer. A particularly strong association with risk has been observed when density is measured using interactive threshold software. This, however, is a labour-intensive process for large-scale studies.

Methods

Our aim was to determine the performance of visually assessed percent breast density as an indicator of breast cancer risk. We compared the effect on risk of density as measured with the mediolateral oblique view only versus that estimated as the average density from the mediolateral oblique view and the craniocaudal view. Density was assessed using a visual analogue scale in 10,048 screening mammograms, including 311 breast cancer cases diagnosed at that screening episode or within the following 6 years.

Results

Where only the mediolateral oblique view was available, there was a modest effect of breast density on risk with an odds ratio for the 76% to 100% density relative to 0% to 25% of 1.51 (95% confidence interval 0.71 to 3.18). When two views were available, there was a considerably stronger association, with the corresponding odds ratio being 6.77 (95% confidence interval 2.75 to 16.67).

Conclusion

This indicates that a substantial amount of information on risk from percentage breast density is contained in the second view. It also suggests that visually assessed breast density has predictive potential for breast cancer risk comparable to that of density measured using the interactive threshold software when two views are available. This observation needs to be confirmed by studies applying the different measurement methods to the same individuals.     

Absence of alternative splicing in bcr-abl mRNA in chronic myeloid leukemia cell lines

The major consequence of the Philadelphia (Ph) translocation in chronic myeloid leukemia (CML) is the formation of a bcr-abl hybrid oncogene encoding a tumor cell-specific protein P210bcr-abl. In contrast to this, in Ph chromosome-positive acute lymphoblastic leukemia (Ph + ALL), a P190bcr-abl can be observed. This P190bcr-abl has been implicated in acute rather than chronic leukemogenesis. Therefore, it can be hypothesized that the transition from chronic to blast phase in CML is accompanied by an alternative splice in the bcr-abl mRNA, which results in a switch of the production of P210bcr-abl into P190bcr-abl. Initial S1 nuclease protection mapping supported this theory. However, this result appears to be based on an artifact in the S1 analysis. By using the polymerase chain reaction we provide evidence for the absence of alternative splicing in bcr-abl mRNA in two CML blast crisis cell lines.