NDUFAF3 variants that disrupt mitochondrial complex I assembly may associate with cavitating leukoencephalopathy

Genetic abnormalities in mitochondrial complex assembling factors are associated with leukoencephalopathy. We present a 1‐year‐old girl with consciousness disturbance after a respiratory infection. Brain MRI revealed leukoencephalopathy with bilaterally symmetrical hyperintensity in the substantia nigra, medial thalamic nuclei, and basal nuclei, as well as cavities in the cerebral white matter and corpus callosum. Lactate levels in the spinal fluid were high, while magnetic resonance spectroscopy of the cerebral white matter and basal nuclei showed high peak lactate levels, suggesting mitochondrial dysfunction. The respiratory enzyme activity of complex I was reduced to 17% to 21% in skeletal muscle. Whole exome sequencing identified compound heterozygous variations in NDUFAF3, involved in the assembly of mitochondrial complex I (c.342_343insGTG:p.117Valdup, c.505C > A:p.Pro169Thr). Two‐dimensional, blue‐native polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate‐PAGE revealed reductions in Q‐module (NDUFS2, NDUFS3, and NDUFA9) and P‐module (NDUFB10 and NDUFB11) subunits, indicating disruption of mitochondrial complex I assembly. Our report expands the spectrum of clinical phenotypes associated with pathogenic variants of NDUFAF3.     

BN大鼠致敏动物模型研究

目的建立经腹腔注射途经给予造模致敏原的BN大鼠致敏动物模型。方法分别在实验第1、5和10天,经腹腔注射给予不同性别(雌性和雄性)和不同周龄(4周龄和8周龄)的BN大鼠,不同剂量(1.00、0.10和0.01mg)的造模致敏原———卵清蛋白(OVA),观察35天。分别于第28、35天内眦取血分离血清,用ELISA方法检测血清中OVA特异性IgE。结果与阴性对照组相比,雌性8周龄BN大鼠中、高剂量组第28、35天血清中OVA特异性IgE浓度显著升高(P<0.05);雄性8周龄BN大鼠低、中剂量组血清中OVA特异性IgE浓度在第28天显著升高(P<0.05),高剂量组血清中OVA特异性IgE浓度在第35天显著升高(P<0.05);雄性4周龄BN大鼠,高剂量组血清中OVA特异性IgE浓度在第35天显著升高(P<0.05)。结论经腹腔注射途径给予不同性别和周龄的BN大鼠不同剂量的OVA,雌性大鼠比雄性大鼠更敏感;8周龄大鼠比4周龄大鼠更敏感;0.10mg或1.00mg的致敏剂量较适合。因此,选用雌性8周龄BN大鼠,经腹腔注射给予0.10mg或1.00mgOVA,35天后即可建立比较理想的BN大鼠致敏动物模型。     

Survival of nerve and Schwann cells in allografts after cyclosporin A treatment

Because nerve and Schwann cells in allografts are rejected by normal rats, we investigated whether or not these neurological cells would survive if rats were treated with the new immunosuppressive drug, Cyclosporin A. Untreated rats rejected nerve and Schwann cells in allografts of ganglia or nerve. On the other hand, nerve and Schwann cells survived in allografts in Cyclosporin A-treated rats even after drug therapy was terminated. These results indicate that Cyclosporin A may be of value if allogenic nerve or Schwann cells are needed to aid in the repair of injured nerve tissue.     

Experimental Graft versus Host Disease in the (BNxLEW)FI rat hybrid: an immunohistochemical study of early disease in oral mucosa

OBJECTIVE: To study the initial cellular events in oral mucosa (tongue) of experimental hyperplastic GVHD. in order to increase our understanding of the possible pathogenic mechanisms that may be shared with eg mercury (and other drug)-induced immunological reactions. MATERIALS AND METHODS: GVHD was induced by one iv. injection of 0.5–1 times 10⁸ BN spleen cells into (BNxLEW)F I hybrid rats. The pre-onset stages of the developing semiallogeneic GVHD were investigated in tongue mucosa by immunohistochemistry and monoclonal antibodies. RESULTS: No detectable tissue infiltrates were found 24 h post induction. The pioneer cells appeared at day 3 and were RTIB⁺ICD2⁺ and RTIB^1–/CD45 (240 kD)^-/ ED I^-/CD45RC-. At day 3, there was also a visible increase in spleen and lymph node size. Between day 3 and 7, there was a statistically significant increase of CD2⁺, RTIB⁺, TCR-αβ⁺, CD4⁺ and CD8⁺ cells, but no increase of NKR-PI⁺ cells. At day 10 there were focal accumulations of CD8⁺ and NKR-PI⁺ cells in subepithelial c.t. and in the basal parts of the adjacent epithelium. Animals not sacrificed earlier, showed signs of disease onset at day 11–14. CONCLUSIONS: The early inflammatory infiltrate in this GVHD model consists of activated T cells of donor origin. We suggest, that these originally ‘naive’ cells migrate initially into lymphoid tissue and following an activation (day 3) enter host's peripheral tissue. Here, (allo-) antigen in constitutively RTIB¹ (and EDI) expressing connective tissue dendritic cells may be immune targets of the primed T cells. Such interaction may lead to focal inflammation (increase of CD2⁺, RTIB⁺, TCR-αβ⁺, CD4⁺ and CD8⁺ cells) and to secondary epithelial damage executed by CD8⁺ and NKR-PI ⁺ lymphocytes.     

Stabilized vision through a bleaching window

The visibility of stimuli flickering at low temporal frequencies was studied with images viewed normally and when stabilized by a new technique (bleached-window stabilization) that produces perfectly stabilized images without attachment to the eye. Contrary to expectation, sensitivity to low-frequency flicker was higher in the stabilized than in the unstabilized case. Several controls exclude the possibility that the paradoxical increase in sensitivity is an artefact of the new technique, and suggest that, in normal viewing, transient activity created by fixational eye-movements can mask the signals arising from the low-frequency flicker.     

Reinfusion of leukemic cells with the autologous marrow graft: preclinical studies on lodging and regrowth of leukemia

To evaluate in quantitative terms the contribution of leukemic cells present in the autologous marrow graft to the occurrence of leukemia relapse after autologous bone marrow transplantation, preclinical studies were performed in a rat model for human acute myelocytic leukemia (BNML). Firstly, the number of leukemic cells which--after intravenous transfer--cause death from leukemia in 50% of the recipient rats proved to be 24.7 cells. Secondly, it appeared that the regrowth of leukemic cells in rats heavily pretreated with high-dose cyclophosphamide and total body irradiation was significantly hampered as compared with non-pretreated controls as judged by survival times (37 and 31 days, respectively after 10(3) BNML cells i.v.). The most likely explanation is treatment-induced damage to the microenvironment. Differences in patterns of lodging of infused leukemic cells were ruled out by comparing the uptake of 51Cr-labeled BNML cells in various organs. Finally, extrapolated from the available rat data on log leukemic cell kill induced by high-dose chemoradiotherapy, an hypothesis is presented relating the total tumor load in man to the clinical outcome of autologous bone marrow transplantation. From this hypothesis it is derived that the minimal number of leukemic cells that causes leukemia upon intravenous transfer varies between 10(4) and 10(6).     

氪激光诱发大鼠脉络膜新生血管的基因表达谱

目的研究氪激光诱发大鼠脉络膜新生血管的基因表达谱。方法对氪激光诱发BN大鼠脉络膜新生血管的脉络膜组织和正常BN大鼠的脉络膜组织进行总RNA的提取,将纯化后的mRNA进行逆转录制备杂交探针,应用含有5705条Oligo DNA的表达谱芯片对氪激光诱发BN大鼠脉络膜新生血管的脉络膜组织和正常BN大鼠的脉络膜组织进行差异表达谱分析。结果在氪激光诱发BN大鼠脉络膜新生血管的基因表达谱中差异表达基因共有46条,其中上调的基因3条,下调的基因43条。它们分别是物质转运、信号传导、代谢、发育、分化、细胞黏附相关基因。结论氪激光诱发脉络膜新生血管的发生发展涉及多基因改变。（中华眼科杂志,2005,41：317-320）     

Temporal and instantaneous connectivity of default mode network estimated using Gaussian Bayesian network frameworks

By probing its functional anatomy, the default mode network (DMN) can be considered consisting of two interacting hub and non-hub subsystems. The hub subsystem includes posterior cingulate cortex (PCC), medial prefrontal cortex (MPFC) and bilateral inferior parietal cortex (IPC). The non-hub subsystem contains inferior temporal cortex (ITC) and (para) hippocampus (HC). In this study, Gaussian Bayesian Network (BN) and Gaussian Dynamic Bayesian Network (DBN) were applied separately to detect the instantaneous and temporal connection relationship within each and between the two DMN subsystems. It was found that the directional instantaneous interactions between the two subsystems were primarily “from non-hub to hub”. The temporal interactions between hub and non-hub regions, on the other hand, are less presented between the two subsystems. The hub subsystem demonstrated both strong instantaneous and temporal interactions among the hub regions, while the non-hub regions were only strongly inter-connected instantaneously but temporally isolated with each other. In addition, one of the hub regions, PCC, appears to be a confluent node and important in the functional integration within the network.     

低温时蛙皮素对IL-1β致热大鼠的降温作用及与PGE_2的相关性

目的：探讨4℃时蛙皮素（BN）的降温作用及其机制。方法：在4℃环境下,以IL-1β致热大鼠为研究对象,采用放免法对下丘脑和血浆中前列腺素E2（PGE2）含量进行同步检测。结果：在IL-1β诱导发热大鼠中,下丘脑及血浆中PGE2含量显著升高（P〈0.01、P〈0.05）;BN降低大鼠正常体温,PGE2含量亦随之显著降低（P〈0.01、P〈0.05）;预先侧脑室注射BN能翻转大鼠IL-1β性发热,且PGE2含量亦明显下降（P〈0.01、P〈0.05）。结论：低温时BN能降低大鼠正常体温和抑制IL-1β性发热,其机制可能是通过抑制PGE2合成与释放实现的。