Immunohistochemical expression of C-myc oncogene,heat shock protein 70 and HLA-DR molecules in malignant cutaneous melanoma

The clinical course of malignant melanomas is frequently unpredictable, although a number of prognostically useful variables can be identified. There is a need for additional markers of prognostic value. In a series of 60 malignant cutaneous melanomas, we analysed the immunohistochemical expression of c-myc proto-oncogene, heat shock protein 70 (HSP70) and HLA-DR molecules in order to investigate their prognostic significance. C-myc, HSP70 and HLA-DR were expressed in 43.3%, 56.6% and 38.3% of all melanoma cases, respectively. Advanced Clark levels (Clark III–V) were significantly associated with c-myc expression rate (P<0.05), HSP70 detection (P<0.01) and HLA-DR positivity (P<0.01). Increased Breslow thickness (>1.5 mm) was related to HLA-DR expression (P<0.05). High mitotic rate was closely associated with c-myc positivity (P<0.05), while HSP70 and HLA-DR expression separately correlated to clinical stage of the disease (P<0.05). The evaluation of these variables may be of immunological and prognostic significance. They were found to be associated with melanocyte subpopulations of the vertical growth phase which are arguably characterized by an increased invasive potential.     

Induction of HSP72 in Rat Liver by Chronic Ethanol Consumption Combined with Exercise: Association with the Prevention of Ethanol-Induced Fatty Liver by Exercise

Ethanol-induced fatty liver in rats was attenuated by repeated running exercise, and the protective effect of exercise was associated with the synergistic expression of heat shock proteins (HSP72). Rats were placed in four groups of six. The two ethanol-fed groups of rats received a liquid diet (Lieber-DeCarli formulation) in which 36% of the calories were derived from ethanol. One group remained sedentary (S/E), whereas the other was trained to run on a rodent treadmill at a speed of 27 m/min, 1 hr/day, 5 days/week, for 7 weeks (R/E). Two other groups–one exercised as previously mentioned (R/C) and one sedentary (S/C)–received control-liquid diets in which the ethanol was isocalorically substituted with a dextran/maltose mixture. The degree of fatty infiltration in liver sections stained with hematoxylin and eosin was graded on a 0–4 scale and the data analyzed by ANOVA on ranks. Ethanol significantly induced fatty infiltration in the S/E group, whereas fatty infiltration in the livers of the R/E group was not different from the S/C group. Electrophoresis and Western blotting of liver homogenates demonstrated that HSP72 was not expressed in either the S/C or S/E groups and was only slightly expressed in the R/C group. The combination of exercise and ethanol, however, resulted in an elevated expression of HSP72 in the R/E group. The content of HSP73 was unaffected by any treatment.     

Regulation of local sweating in sleep-deprived exercising humans

Summary Thermoregulatory sweating [total body (m _sw,b), chest (m _sw,c) and thigh (m _sw,t) sweating], body temperatures [oesophageal (T _oes) and mean skin temperature (T _sk)] and heart rate were investigated in five sleep-deprived subjects (kept awake for 27 h) while exercising on a cycle (45 min at approximately 50% maximal oxygen consumption) in moderate heat (T _air andT _wall at 35° C. Them _sw,c andm _sw,t were measured under local thermal clamp (T _sk,1), set at 35.5° C. After sleep deprivation, neither the levels of body temperatures (T _oes,T _sk) nor the levels ofm _{sw, b},m _{sw, c} orm _{sw, t} differed from control at rest or during exercise steady state. During the transient phase of exercise (whenT _sk andT _sk,1 were unvarying), them _{sw, c} andm _{sw, t} changes were positively correlated with those ofT _oes. The slopes of them _{sw, c} versusT _oes, orm _{sw, t} versusT _oes relationships remained unchanged between control and sleep-loss experiments. Thus the slopes of the local sweating versusT _oes, relationships (m _{sw, c} andm _{sw, t} sweating data pooled which reached 1.05 (SEM 0.14) mg·cm^–2·min^–1°C^–1 and 1.14 (SEM 0.18) mg·cm^–2·min^–1·°C^–1 before and after sleep deprivation) respectively did not differ. However, in our experiment, sleep deprivation significantly increased theT _oes threshold for the onset of bothm _{sw, c} andm _{sw, t} (+0.3° C,P<0.001). From our investigations it would seem that the delayed core temperature for sweating onset in sleep-deprived humans, while exercising moderately in the heat, is likely to have been due to alterations occurring at the central level.     

脊髓损伤后热休克蛋白27、表皮脂肪酸结合蛋白和金属蛋白酶组织抑制因子-1的基因表达及甲基强的松龙对其表达的影响

目的研究脊髓损伤后热休克蛋白27(HSP27)、表皮脂肪酸结合蛋白(FABPs)和金属蛋白酶组织抑制因子-1(TIMP-1)的基因表达及甲基强的松龙(MP)对其表达的影响.方法SD大鼠30只.随机分为假手术组、单纯脊髓损伤组(损伤组)及脊髓损伤+大剂量MP治疗组(MP组),每组10只.应用改良的Allen's打击法致T8脊髓损伤.MP组大鼠伤后即刻从尾静脉内注射大剂量MP(30mg/kg).损伤后24h切取损伤平面上下0.5cm的脊髓组织,进行RT-PCR反应,检测HSP27、FABPs和TIMP-1的基因表达.结果术后24h假手术组HSP27、FABPs和TIMP-1的基因表达相对丰度分别为0.0643±0.0152、0.6413±0.1005和0.7091±0.0577;损伤组上述三个因子的表达升高,分别为1.0013±0.3861、1.2187±0.2851和0.8971±0.1092,与假手术组比较差异有显著性(P＜0.01、P＜0.05、P＜0.05);MP组上述三个因子的表达继续升高,分别为1.2858±0.1384、1.7122±0.1766和1.2081±0.1093,与损伤组比较差异有显著性(P＜0.05、P＜0.01和P＜0.01).结论脊髓损伤后,邻近损伤处的脊髓组织中HSP27、FABPs及TIMP-1的基因表达显著增高,大剂量MP能进一步促进三个因子表达,发挥组织保护作用.     

载氧血红蛋白纯化工艺研究

目的改善心脑血管缺氧载氧药物是一种创新药物。由于它半径比红细胞小400~1 000倍,易于通过毛细血管,给缺血组织及时供氧,迅速缓解或纠正缺氧状态,达到治疗抢救目的。血红蛋白的纯化工艺是载氧药物研制的重要工艺步骤。方法本研究建立了一套通过热敏法分离纯化人脐带血血红蛋白的工艺以及较为完善的纯化血红蛋白质量检测指标。结果与现有的纯化方式相比,热敏法操作简便,仪器设备造价低廉,纯化与病毒灭活同时进行,得到的纯化产品损失少,纯度高,各项理化指标达到国际水平。结论本工艺适用于规模制备纯化血红蛋白,为进一步研制治疗心脑血管缺氧载氧药物创造了有利条件。     

Continuous measurement of oxygen consumption using the reversed fick method

We developed a continuous oxygen consumption (Vo₂) measurement system employed the reversed Fick method, in which Vo₂ in computed from continuously measured sured arterial and mixed venous oxygen saturation assed by pulse oximetry and mixed venous oximetry, respectively, and cardiac output by the heat deprivation technique. This system was compared with the conventional intermittent reversed fick method in 7 patients during surgery and with indirect calorimetry in 4 intensive care unit (ICU) patients. The Vo₂ measured by the continuous reversed Fick method showed a high correlation with those simultaneously measured by the intermittent Fick method (r=0.97,P<0.01) and by indirect calorimetry (r=0.74,P<0.01). The 95% confidence limits (bias±2 SD) of the continuous reversed Fick method were −0.6±45 ml·min⁻¹ with the intermittent Fick method and −31±56 ml·min⁻¹ with indirect calorimetry. The continuous Fick method is in satisfactory agreement with the conventional methods for the measured of Vo₂ and potentially allows for convenient assessment of Vo₂ in critically ill patients. This study was supported in part by Grants-in-Aid for the Encouragement of Young Scientists 01771185 and 04857171 from the Ministry of Education, Science and Culture of Japan     

‘Ischemic tolerance’ phenomenon detected in various brain regions

We investigated the effects of mild and non-lethal ischemic insult on neuronal death following subsequent lethal ischemic stress in various brain regions, using a gerbil model of bilateral cerebral ischemia. Single 10-min ischemia consistently caused neuronal damage in the hippocampal CA1, CA2, CA3 and CA4, layer III/IV of the cerebral cortex, dorsolateral part of the caudoputamen and ventrolateral part of the thalamus. On the other hand, in double ischemia groups, 2-min ischemic insult 2 days before 10-min ischemia exhibited significant protection in the CA1 and CA3 of the hippocampus, the cerebral cortex, the caudoputamen and the thalamus. Five-min ischemic insult 2 days before 10-min ischemia also showed protective effect in the same areas as those of 2-min ischemia except for the CA1 region of the hippocampus, while 1-min ischemic insult exhibited no protective effect in any brain regions. In the immunoblot analysis, both 2- and 5-min ischemia caused increased synthesis of heat shock protein 72 (HSP 72) in the hippocampus, but 1-min ischemia did not. The present study demonstrated that the ‘ischemic tolerance’ phenomenon was widely found in the brain and also suggested that ischemic treatment severe enough to cause HSP 72 synthesis might be needed for induction of ‘ischemic tolerance’.     

硫酸锌对大鼠移植胰腺再灌注损伤的保护作用

Objective:To study the protective effects of the heat shock protein 70 （HSP70）induced by zinc sulfate on reperfusion injury following pancreaticoduodenal transplantation in rats.Methods :The homologous male Wistar rat model of heterotopic total pancreaticoduodenal transplantation was used. The ZnSO4 treated rats received the intravenous injection of Zn2+5 mins before and after operation at a dose of 5 mg/kg (Zn 1 group),10 mg/kg(Zn 2 group) and 15 mg/kg(Zn 3 group), and the control group with the same volume of saline. The tissue concentration of HSP70 was determined using Western Blot. In addition，blood sugar (BG) and serum concentration of amylase and lipase were examined 24h after transplantation, and the activity of myeloperoxidase (MPO) in the pancrease graft was measured at the same time. Histological observation was performed.Results:Light microscopic studies showed that histomorphological changes of pancreas in Zn 2 group and Zn 1 group were much less than those in control group and Zn 3 group. The value of BG and serum lipase and MPO in Zn 2 group ＜ Zn 1 group 相似文献   

接触性热痛诱发电位检测方法的建立

目的 建立接触性热痛诱发电位(CHEP)的检测方法,估测介导此诱发电位的外周神经传导速度.方法 受试者取卧位,应用CHEP刺激器,于两个强度水平(49.5℃和54.5℃)应用可调节脉冲,刺激部位为鱼际肌、手背、前臂的掌侧面.受试者在每次刺激后,按照视觉模拟评分标准对刺激强度分级.以Keypoint仪器记录,记录点为Cz和Pz.测定刺激强度和疼痛分级的关系、诱发电位的主要成分及外周神经传导速度.结果 刺激强度和疼痛分级的关系为:49.5℃和54.5℃刺激鱼际肌皮肤,疼痛分级分别为(3.2±0.3)、(4.4±0.5)级;54.5℃刺激手背和前臂掌侧面皮肤,疼痛分级分别为(6.3±0.8)、(7.2±0.5)级.于记录点记录到3个主要成分:Cz/N550、Cz/P750和Pz/P1000.介导此诱发电位的外周神经传导速度分别为(12.9±7.5)、(1.7±0.4)m/s,分别与Aδ纤维和C纤维的传导速度相对应.结论 CHEP能较为稳定、可靠地引出,介导此诱发电位的外周神经为Aδ纤维和C纤维.     

Hypohydration effects on thermoregulation during moderate exercise in the cold

Hyperosmotic hypovolemia impairs vasoconstriction during sedentary cold exposure. The purpose of this study was to determine whether hypohydration alters thermoregulation and cardiovascular responses to exercise in cold air. On four occasions, eight males [35.1 (2.7) years, 175.5 (3.1) cm, 73.3 (2.6) kg, 57.2 (2.6) ml kg^–1 min^–1 maximal oxygen uptake (O_2max), 19.6 (2.4)% fat] walked, in t-shirt, shorts, and shoes, at 50% O_2max, for 60 min in either a 4°C (Cold) or a 25°C (Temperate) environment in both hypohydrated state (HYPO, –4% body mass) and euhydrated state (EU). During exercise–cold stress, rectal temperature (T_re), mean weighted skin temperature, heart rate (HR), cardiac output (CO), and stroke volume (SV) were measured every 20 min. Mean weighted skin temperature values were not different between HYPO and EU but were lower (P<0.05) in Cold versus Temperate trials. T_re was not different (P>0.05) between HYPO–Cold and EU–Cold. CO and SV were not different within hydration states and were not different between Cold and Temperate trials (P<0.05). HR was not different between HYPO–Cold and EU–Cold. These data demonstrate that moderate intensity exercise in the cold while hypohydrated does not alter metabolic heat production, skin temperatures and heat loss, nor does it increase thermoregulatory and cardiovascular strain.