阿霉素致兔心脏毒性心肌细胞凋亡及相关基因bcl-2，bax蛋白表达变化

目的:观察不同剂量阿霉素心脏毒性心肌细胞凋亡情况及相关基因bcl-2,bax蛋白表达变化。方法:实验于2005-06/2006-08在大连医科大学附属第二医院实验中心完成。选用健康新西兰纯种白兔42只,按随机数字表法分成4组:①对照组(n=10),给予2mL/kg的生理盐水静脉注射,1次/周,共8周。②阿霉素4mg/kg组(n=10),给予阿霉素2mg/kg,以生理盐水稀释耳缘静脉注射,1次/周,共2周。③阿霉素8mg/kg组(n=10),同样方法给予阿霉素,共4周。④阿霉素16mg/kg组(n=12),同样方法给予阿霉素,共8周。12周后麻醉处死兔,取心肌组织,应用原位末端标记法标记凋亡的心肌细胞;应用免疫组织化学法检测bcl-2,bax蛋白的表达,以平均吸光度表达。结果:阿霉素16mg/kg组兔死亡3只,最后39只兔进入结果分析。①透射电镜观察结果:对照组、阿霉素4mg/kg组未见心肌细胞凋亡;阿霉素8mg/kg组和阿霉素16mg/kg组均观察到细胞核变小、核染色质浓缩、边聚的凋亡心肌细胞。②心肌细胞凋亡指数:对照组、阿霉素4mg/kg组未见心肌细胞凋亡;阿霉素8mg/kg组和阿霉素16mg/kg组心肌细胞凋亡指数显著高于对照组(P<0.01)。③心肌bcl-2与bax蛋白表达:阿霉素8,16mg/kg组bcl-2蛋白表达显著低于对照组(P<0.01),bax蛋白表达显著高于对照组(P<0.01),bcl-2/bax显著低于对照组(P<0.01)。阿霉素16mg/kg组bcl-2蛋白表达显著低于阿霉素8mg/kg组(P<0.01),bax蛋白表达显著高于阿霉素8mg/kg组(P<0.01)。与对照组相比,阿霉素4mg/kg组bcl-2,bax蛋白表达及bcl-2/bax无明显变化(P>0.05)。结论:阿霉素4mg/kg组可能因阿霉素剂量小未出现心肌细胞凋亡,阿霉素8,16mg/kg组可见典型凋亡心肌细胞,并且呈一定的量效关系,进一步说明细胞凋亡机制参与了阿霉素心脏毒性的病理过程,其作用与下调bcl-2基因的蛋白表达、上调bax基因的蛋白表达有关。     

Postural and Metabolic Benefits of Using a Forearm Support Walker in Older Adults With Impairments

Objective

To investigate the postural and metabolic benefits a walker with adjustable elbow support (LifeWalker [LW]) can provide for ambulation in population with impairment. The clinical outcomes from the elbow support walker will be compared with standard rollator (SR) and participants predicate device (PD).

Effects of Sibutramine on Gastric Emptying, Intestinal Motility and Rectal Tone in Dogs

The aim of this study was to evaluate the effects of sibutramine on gastric emptying, small-bowel contractions, rectal tone and compliance, and gastrointestinal myoelectrical activity. The study was performed in 14 dogs. It was composed of three separate experiments: gastric emptying of liquids and gastrointestinal slow waves; small-bowel contractions; and rectal tone and rectal compliance. Each experiment included two sessions: a control session and a treatment session with sibutramine (5 mg/kg orally) administrated 2 h before the study. Sibutramine significantly accelerated liquid gastric emptying at 75 and 90 min after the meal but did not alter gastrointestinal slow waves. Gastric emptying at 75 and 90 min was 61.42 ± 7.71 and 66.32 ± 7.67% in the control session, and increased to 71.27 ± 5.14 and 75.93 ± 5.29% in the session with sibutramine (p < 0.05, vs. control). Sibutramine significantly inhibited postprandial small-bowel contractions. Sibutramine did not alter the rectal tone, but significantly increased rectal compliance. Sibutramine accelerates gastric emptying of liquids but inhibits small-bowel contractions. These findings suggest the peripheral mechanisms of sibutramine in reducing food intake and causing weight loss in obesity patients.     

Human cytomegalovirus-induced immunosuppression. Relationship to tumor necrosis factor-dependent release of arachidonic acid and prostaglandin E2 in human monocytes.

Cytomegalovirus (CMV) has been associated with immunosuppression. Previously CMV was reported to interfere with signal transduction pathways in T cells. In this report the mechanisms underlying CMV-mediated immunosuppression were examined. Supernatants of CMV (Strains C-87, AD-169)-infected primary human monocyte (MO) cultures inhibited mitogenic T cell proliferative responses by > 95%. The inhibitory activity was observed 24 h through day 7 postinfection. The infection of MO was associated with a sustained elevation of intracellular levels of cAMP and the release of arachidonic acid (AA) and its metabolite PGE2 (activator of adenylate cyclase) in culture supernatants. The AA release was incidentally associated with TNF-alpha production. Monoclonal antibodies to TNF-alpha and pentoxyphylline (inhibitor of TNF synthesis) inhibited both AA and PGE2 release. The release of AA required protein synthesis and occurred under conditions consistent with the expression of CMV immediate early genes. Treatment of MO cultures at time of infection with 100 microM indomethacin or 1 microg of TNF-alpha mAb abolished the CMV-induced T cell inhibitory activity of the supernatants by 100%. These data suggest that TNF dependent release of AA and PGE2 contributes to CMV-induced immunosuppression.     

Two Cycles of High Dose Chemotherapy with Autologous Bone Marrow Support for Patients with Locally Advanced Breast Cancer

Abstract: Purpose: To examine the impact of two cycles of high dose chemotherapy (HDC) with autologous bone marrow rescue (ABMR) in the treatment of women with locally advanced breast cancer. Patients and Methods: Twenty-three patients not exhibiting progressive disease to conventional dose therapy (ltx) were eligible for HDC. Conventional dose regimens used were the CAMFTP regimen (n= 6), 5-FU, doxorubicin and cyclophosphamide (n= 3), cyclophosphamide, methotrexate and 5-FU (n= 1), or doxorubicin/cyclophosphamide (n= 13). HDC on each cycle consisted of etoposide 625 mg/m², cyclophosphamide 6 gr/m², carboplatin 2 gr/m² with ABMR. Median age of the patients was 40 years. Results: Seventeen patients (74%) underwent two cycles of HDC; 6 received only one cycle due to insurance refusal to pay for C2 (1), toxicity from C1 (4), death on C1(1). There were 2 transplant-related deaths due to fungal infections 1 each on C1 and C2. Four patients achieved complete remission (CR) with Itx, 18 achieved partial remission (PR), and 1 had stable disease (SD). One patient was converted from PR to CR with HDC. There are 9/23 (39%) patients alive and progression-free with median follow-up of 27 months. (range 21-41 + months). Twelve of the 23 (52%) have progressed at a median of 7 months (range 4-32) from bone marrow transplant (BMT) and there were 2 early deaths (9%). Six patients received only one cycle of HDC and 2 of these are alive and progression-free at 36 and 38 months of follow-up. Of the 17 completing two cycles of HDC, 7/17 (41%) are alive and progression-free with follow-up of 21-41 months. The median progression-free survival (PFS) for the entire group is 13 months and median overall survival is 21 months (range 1–41 + mos). Conclusion: Despite the use of two cycles of HDC with ABMR, systemic relapse remains the major obstacle to cure in women with locally advanced breast cancer; there is a need to develop more effective preparative rgimens.     

Effect of the fragile X anomaly on body proportions estimated by pedigree analysis

Loesch DZ, Sampson ML. Effect of the fragile X anomaly on body proportions estimated by pedigree analysis.
Clin Genet 1993: 44: 82–88. © Munksgaard, 1993
The purpose of this study was to determine the effect of the fragile X syndrome on limb (upper limb length) and facial (ear length) measurements in relation to body height, which was considered as a covariate. The analysis was performed in 52 fragile X Caucasian families, including affected individuals as well as their normal relatives. The maximum likelihood analysis of complex pedigrees, under the assumption of multivariate normality, was used to select the best genetic model and to estimate model parameters. This method allowed us to test various assumptions concerning the effect of normal hereditary variation, as well as of genetic anomaly and other relevant factors, in the mean and variance of a quantitative trait, and to obtain the maximum likelihood parameters for these effects. The results demonstrated that, if the family factor is accounted for in a model, the fragile X condition affects growth of both upper limb length and ear length, disproportionately to body height.     

Epithelial and Stromal Estrogen and Progesterone Receptor Expression in Endometrial Cancer: True Color Computer-Assisted Image Analysis versus Subjective Scoring

Immunohistochemical methods provide the opportunity to evaluate the staining reaction in different histologic compartments of malignant tumors. Eighty-four formalin-fixed, paraffin-embedded and immunohistochemically stained endometrial cancer specimens were assessed for estrogen receptor (ER) and progesterone receptor (PR) expression by conventional light microscopy, a light microscopy scoring system, and by true color computer-assisted image analysis. Measurements of mean optical density (MOD) in the epithelium as well as in the stroma of the tumor were performed. A negative correlation was established between the MOD of ER and PR staining in the nuclei of the epithelium and the MOD of PR staining in the stroma of the tumor vs histological stage (Spearman correlation coefficient −0.32/P< 0.004, −0.23/P< 0.03, −0.26/P< 0.02, respectively) and depth of myometrial invasion (Spearman correlation coefficient −0.34/P< 0.002, −0.24/P< 0.02, −0.25/P< 0.02, respectively). The staining pattern in endometrial cancer was heterogeneous and %PA (percentage of positive stained area) and MOD were therefore linked by multiplication in order to correct for this potentially confounding phenomenon. A negative correlation with histological stage (Spearman correlation coefficient −0.29/P< 0.007) and depth of myometrial invasion (Spearman correlation coefficient −0.34/P< 0.001) was found for PR staining in the stroma of the tumor. MOD and subjective ranking of staining intensity showed a high correlation as well as %PA and subjective estimation of stained surface. ER and PR content in the epithelium and also PR content in the stroma of endometrial cancer appear to be of value in the assessment of steroid hormone receptor status. This may be indicative of stromal–epithelial interaction.     

Endothelin, vasopressin, and substance P like immunoreactivity in cultured and intact epithelium from rabbit trachea.

BACKGROUND: The control of airways reactivity is essential to our understanding of disease processes such as asthma. Many studies have examined the neural control of the airways, but more recently there has been evidence to show that the epithelium lining the airways may influence airways reactivity. METHODS: Rabbit tracheal epithelial cells were dispersed with enzymes, grown in primary culture and fixed. Tissue from intact tracheas was also sampled and fixed. Localisation of the vasoactive substances endothelin-1, arginine-vasopressin, and substance P was investigated by immunolabelling techniques. RESULTS: Scattered immunolabelling to endothelin-1, arginine-vasopressin, and substance P was found throughout the cultures (with < 20% of cells staining positively to each antibody). At the ultrastructural level this immunoreactivity was found in the cytoplasmic matrix. In addition, immunoreactivity of intact tissue to endothelin-1, arginine-vasopressin, and substance P was examined and positively staining cells were found to be scattered through the epithelium. CONCLUSIONS: The presence of these vasoactive substances within the epithelium lining the airways supports the view that epithelial cells may provide an additional mechanism in the control of airways reactivity.     

Seasonal variations in circadian levels of serum prolactin in striped mullet,Mugil cephalus

Plasma concentrations of prolactin were estimated by radioimmunoassay throughout a day at three seasons of the year (summer, fall, and winter) in the striped mullet, Mugil cephalus. Daily rhythms were found at each season. In addition, the patterns of the rhythms with respect to the daily photoperiod differed from one another. The data are consistent with the hypothesis that a seasonal change in the daily rhythm of prolactin has an important role in regulating the seasonal changes in physiology of some animals.