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死亡前的住院时间和胰腺组织病理学:对未来研究的启示。

Hospital time prior to death and pancreas histopathology: implications for future studies.

机构信息

Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, USA.

Department of Diabetes and Cancer Discovery Science, Diabetes and Metabolism Research Institute, City of Hope/Beckman Research Institute, 1500 East Duarte Road, Duarte, CA, 91010-3000, USA.

出版信息

Diabetologia. 2018 Apr;61(4):954-958. doi: 10.1007/s00125-017-4494-x. Epub 2017 Nov 11.

Abstract

AIMS/HYPOTHESIS: Diabetes research studies routinely rely upon the use of tissue samples from human organ donors. It remains unclear whether the length of hospital stay prior to organ donation affects the presence of cells infiltrating the pancreas or the frequency of replicating beta cells.

METHODS

To address this, 39 organ donors without diabetes were matched for age, sex, BMI and ethnicity in groups of three. Within each group, donors varied by length of hospital stay immediately prior to organ donation (<3 days, 3 to <6 days, or ≥6 days). Serial sections from tissue blocks in the pancreas head, body and tail regions were immunohistochemically double stained for insulin and CD45, CD68, or Ki67. Slides were electronically scanned and quantitatively analysed for cell positivity.

RESULTS

No differences in CD45, CD68, insulin, Ki67 or Ki67/insulin cell frequencies were found when donors were grouped according to duration of hospital stay. Likewise, no interactions were observed between hospitalisation group and pancreas region, age, or both; however, with Ki67 staining, cell frequencies were greater in the body vs the tail region of the pancreas (∆ 0.65 [unadjusted 95% CI 0.25, 1.04]; p = 0.002) from donors <12 year of age. Interestingly, frequencies were less in the body vs tail region of the pancreas for both CD45 cells (∆ -0.91 [95% CI -1.71, -0.10]; p = 0.024) and insulin cells (∆ -0.72 [95% CI -1.10, -0.34]; p < 0.001).

CONCLUSIONS/INTERPRETATION: This study suggests that immune or replicating beta cell frequencies are not affected by the length of hospital stay prior to donor death in pancreases used for research.

DATA AVAILABILITY

All referenced macros (adopted and developed), calculations, programming code and numerical dataset files (including individual-level donor data) are freely available on GitHub through Zenodo at https://doi.org/10.5281/zenodo.1034422.

摘要

目的/假设:糖尿病研究通常依赖于从人体器官捐献者的组织样本。目前尚不清楚在器官捐献前的住院时间长短是否会影响浸润胰腺的细胞存在或复制β细胞的频率。

方法

为了解决这个问题,将 39 名无糖尿病的器官捐献者按年龄、性别、BMI 和种族分为三组,每组三人。在每组中,根据器官捐献前住院时间的长短,将捐献者分为三组:<3 天、3-<6 天或≥6 天。对胰腺头部、体部和尾部组织块的连续切片进行胰岛素和 CD45、CD68 或 Ki67 的免疫组织化学双重染色。对幻灯片进行电子扫描,并对细胞阳性率进行定量分析。

结果

根据住院时间长短对供体进行分组时,未发现 CD45、CD68、胰岛素、Ki67 或 Ki67/胰岛素细胞频率存在差异。同样,在住院组与胰腺区域、年龄或两者之间也没有观察到相互作用;然而,在用 Ki67 染色时,与胰腺尾部相比,年龄<12 岁的供体胰腺体部的细胞频率更高(∆0.65 [未调整的 95%CI 0.25, 1.04];p=0.002)。有趣的是,与胰腺尾部相比,CD45 细胞(∆-0.91 [95%CI-1.71, -0.10];p=0.024)和胰岛素细胞(∆-0.72 [95%CI-1.10, -0.34];p<0.001)的频率更低。

结论/解释:这项研究表明,在用于研究的胰腺中,供体死亡前的住院时间长短不会影响免疫或复制β细胞的频率。

数据可用性

所有引用的宏(采用和开发)、计算、编程代码和数值数据集文件(包括个体供体数据)均可在 GitHub 上通过 Zenodo 免费获得,网址为 https://doi.org/10.5281/zenodo.1034422。

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