The significance of total creatine kinase activity and isozyme determinations in cerebrospinal fluid of neurological patients

Total CK activity is often increased in cerebrospinal fluid samples in neurological diseases (35%). These increased levels are frequently caused by CK M-chain activity and appear to have no diagnostic relevance. Furthermore, an obvious concentration gradient for total CK activity was often observed in two subsequent tubes from the same lumbar puncture. In this study, CK non-M activity is measured, being the sum of all CK activity not caused by the M-chain. A bioluminescence technique using anti-M-inhibiting antibodies was used for this purpose. In two subsequent tubes from the same lumbar puncture a difference of 8% in CK non-M activity was found. A similar gradient could be observed for total protein. Retrospectively, the correlation between CK non-M levels and the amount of brain tissue damage was studied in 81 neurological patients and in 19 healthy subjects. There was an obvious relation between the extent of brain tissue damage and the CSF CK non-M levels. The clinical results in this study are promising and justify a prospective study of the diagnostic relevance of this parameter in CSF in various patient groups.     

Development of CAR T Cells Expressing a Suicide Gene Plus a Chimeric Antigen Receptor Targeting Signaling Lymphocytic-Activation Molecule F7

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Cardiac function and ischaemic tolerance during acute loss of metabolic control in the diabetic BB Wor rat

Abstract The effect of loss of metabolic control, by with-holding insulin treatment, on reperfusion recovery of cardiac function following ischaemia was studied in the spontaneously diabetic “BB” Wor rat. The study involved a group of insulin-treated diabetic BB rats (insulin-treated) and diabetic BB rats in which insulin treatment was withheld 24 h prior to study (insulin-withdrawn). Hearts were isolated and perfused at a constant left atrial filling pressure of 15 cm H₂O and aortic afterload resistances of 100 and 140 cm H₂O. Hearts were then subjected to 20 min of ischaemia followed by 30 min of reperfusion. Withdrawing insulin treatment from the BB Wor rat resulted in a dramatic increase in the levels of plasma glucose and free fatty acids. Hearts from these rats perfused under aerobic conditions demonstrated reductions in heart rate, positive and negative dP/dt, cardiac output and left ventricular minute work, whereas diastolic pressure was elevated. Following ischaemia, recovery of cardiac function in the insulin-treated BB Wor rat returned to preischaemic levels, whereas hearts from insulin-withdrawn rats displayed impaired recovery. Throughout reperfusion, heart rate, positive dP/dt, cardiac output and left ventricular minute work remained significantly lower in hearts from insulin-withdrawn rats compared to treated rats. Our results indicate that acute loss of metabolic control increases the sensitivity of the heart to ischaemia, even in the acutely diabetic BB Wor rat.     

空腹越野跑对血糖和游离脂肪酸、糖原磷酸化酶BB和心型脂肪酸结合蛋白的影响

目的空腹剧烈运动可造成运动性低血糖,严重时导致心肌损伤。探讨空腹5000 m越野跑对尚未适应训练的新兵心肌主要供能物质的影响,以及监测不易发现的轻微心肌损伤,为部队的新兵制订合理的训练方案提供实验依据。方法入伍1个月男新兵30名,晨起洗漱后空腹越野跑5000 m,分别观察跑前与跑后即刻和4 h血糖和糖原磷酸化酶BB(glyco-gen phosphorylase isoenzyme BB,GPBB)、游离脂肪酸和心型脂肪酸结合蛋白(heart-type fatty acid-binding protein,H-FABP)的变化。结果血糖由运动前的(3.78±0.52)mmol/L升至运动后即刻的(4.36±0.48)mmol/L(P<0.01)。游离脂肪酸由运动前的(141.48±58.52)μmol/L降至运动后即刻的(98.13±33.16)μmol/L和4h的(99.78±18.76)μmol/L(P<0.01)。GPBB由运动前的(22.28±3.47)ng/ml升至运动后即刻的(26.44±3.57)ng/ml和4h的(29.36±5.08)ng/ml(P<0.01)。H-FABP由运动前的(16....     

Recombinant human platelet‐derived growth factor BB (rhPDGF‐BB) and beta‐tricalcium phosphate/collagen matrix enhance fracture healing in a diabetic rat model

Diabetes mellitus is a common systemic disease that has been associated with poor fracture healing outcomes. The mechanism through which diabetes impairs bone regeneration is unknown. One possible mechanism may be related to either decreased or uncoordinated release of local growth factors at the fracture site. Indeed, previous studies have found reduced platelet‐derived growth factor (PDGF) levels in the fracture callus of diabetic rats, suggesting that local application of PDGF may overcome the negative effects of diabetes and promote fracture healing. To test this hypothesis, low (22 µg) and high (75 ug) doses of recombinant human PDGF‐BB (rhPDGF‐BB) were applied directly to femur fracture sites in BB Wistar diabetic rats that were then compared to untreated or vehicle‐treated animals. rhPDGF‐BB treatment significantly increased early callus cell proliferation compared to that in control specimens. Low dose rhPDGF‐BB treatment significantly increased callus peak torque values (p < 0.05) at 8 weeks after fracture as compared to controls. High dose rhPDGF‐BB treatment increased callus bone area at 12 weeks postfracture. These data indicate that rhPDGF‐BB treatment ameliorates the effects of diabetes on fracture healing by promoting early cellular proliferation that ultimately leads to more bone formation. Local application of rhPDGF‐BB may be a new therapeutic approach to treat diabetes‐impaired fracture healing. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 1074–1081, 2009     

VEGF-C与PDGF-BB在结肠癌组织中的表达

目的探讨结肠癌组织中血小板衍生生长因子BB（PDGF-BB）、血管内皮生长因子C（VEGF-C）的表达,及其与肿瘤临床病理参数之间的关系;分析在结肠原发癌与相应淋巴结转移癌中VEGF-C、PDGF-BB表达是否存在差异。方法收集结肠癌组织50例、淋巴结转移癌30例及癌旁正常组织15例,应用免疫组化SP法检测VEGF-C,PDGF-BB在癌旁正常组织、结肠癌和淋巴结转移癌中的表达。结果结肠癌组织中VEGF-C阳性表达率显著高于癌旁正常组织（P〈0.05）;VEGF-C的表达与结肠癌的浸润深度、淋巴结转移有关（均P〈0.05）,与病人性别、肿瘤大小及分化程度无关（P〉0.05）。PDGF-BB在结肠癌组织中的阳性表达率显著高于癌旁正常组织（P〈0.05）;PDGF-BB的表达与肿瘤的浸润深度有关（P〈0.05）,与病人的性别、肿瘤的大小、分化程度及淋巴结转移无关（P〉0.05）。PDGF-BB、VEGF-C2者之间的表达呈显著正相关（r=0.572,P〈0.05）。PDGF-BB、VEGF-C在淋巴结转移癌中的表达率均高于其相应的原发癌组织,但无统计学意义（均P〉0.05）。结论VEGF-C表达与结肠癌的浸润及淋巴结转移有关;PDGF-BB的表达与结肠癌浸润有关。PDGF-BB、VEGF-C在结肠癌中的表达呈正相关。肿瘤原发癌与淋巴结转移癌中VEGF-C、PDGF-BB的表达无异质性。     

4-1BB／4-1BBL在T细胞免疫应答及疾病发生中的作用

共刺激分子4-1BB和4-1BB配体（4-1BBL）属于肿瘤坏死因子／肿瘤坏死因子受体（TNF／TN—FR）超家族的重要成员,分别表达在活化的T细胞及树突状细胞（DC）上。4-1BB与4-1BBL相互作用产生的共刺激信号能够促进T细胞增殖、分化以及细胞因子的产生。4-1BB／4—1BBL信号途径在自身免疫性疾病、肿瘤、病毒感染等疾病的发生、发展过程中起着重要的免疫调节作用。干预调节4-1BB／4-1BBL信号途径有望为疾病的免疫治疗提供新的思路。     

TIMP-3 and MMP-3 contribute to delayed inflammation and hippocampal neuronal death following global ischemia

Hippocampal neuronal death following transient global ischemia in the mouse takes days to occur, providing a potential timeframe for therapeutic intervention. Since matrix metalloproteinase-3 (MMP-3) enhances inflammation and tissue inhibitor of metalloproteinases-3 (TIMP-3) promotes apoptosis in ischemia, we hypothesized that they are involved in neuronal death secondary to transient global ischemia. Timp-3 knockout (T3KO) and wild type (T3WT) mice underwent 30 min bilateral carotid artery occlusion (BCAO), which causes hippocampal neuronal death 7 days after reperfusion. Mice lacking the Timp-3 gene have significantly less astrocytosis, microglial reactivity, MMP-3 activity and neuronal cell death. In addition, T3KO mice had decreased tumor necrosis factor (TNF) receptor-1 (TNFR1) expression and increased TNF-α converting enzyme (TACE) activity. Mmp-3 KO mice with a similar BCAO showed significantly fewer microglial cells, reduced TNF-α expression, and less neuronal death than the Mmp-3 WT. To see if TIMP-3 and MMP-3 cell death pathways were independent, we blocked MMPs with the broad-spectrum MMP inhibitor, BB-94, on days 3 through 6 of reperfusion in T3WT and T3KO mice. BB-94 rescued hippocampal neurons at 7 days in both T3WT and T3KO mice, but significantly fewer neurons died in T3KO mice treated with BB-94. Our results indicate a novel additive role for TIMP-3 and MMP-3 in delayed neuronal death, and show that delayed treatment with MMP inhibitors can be used to reduce hippocampal death.     

Investigation of the immunogenicity of p-phenylenediamine and Bandrowski's base in the mouse

p-Phenylenediamine (PPD) exposure is associated with T-cell mediated contact dermatitis. T-cells from allergic patients proliferate following exposure to PPD and the oxido-conjugation product Bandrowski's base (BB). Both compounds are classified as sensitizers in the local lymph node assay; however, because of their instability the nature of the antigenic determinant remains ill-defined. The aim of this study was to explore the immunogenic potential of PPD and BB in mice. Spleen cell proliferation and cytokine secretion was measured ex vivo following antigen recall with soluble PPD or BB and either irradiated or glutaraldehyde fixed, antigen pulsed dendritic cells from syngeneic mice. Glutathione was added to certain incubations. LC–MS analysis and solvent extraction were used to monitor the fate of [¹⁴C]BB in culture and the extent of BB binding, respectively. Spleen cells from BB exposed, but not PPD- or vehicle-exposed, mice proliferated when stimulated with BB. Proliferating cells secreted high levels of IFN-γ, GM-CSF and IL-2. Stimulation with PPD instigated low levels of proliferation. Irradiated, but not fixed, dendritic cells pulsed with BB stimulated proliferation signifying a classical hapten mechanism involving irreversible BB binding to protein and processing. BB bound preferentially to serum protein when incubated together with cells and serum. Degradation of BB in the presence of glutathione was associated with a stronger stimulation of specific T-cells at higher BB concentrations. These data demonstrate that BB is a potent immunogen in the mouse.