Effects of protein kinase C activators on phorbol ester-sensitive and - resistant EL4 thymoma cells

Phorbol ester-sensitive EL4 murine thymoma cells respond to phorbol 12- myristate 13-acetate with activation of ERK mitogen-activated protein kinases, synthesis of interleukin-2, and death, whereas phorbol ester- resistant variants of this cell line do not exhibit these responses. Additional aspects of the resistant phenotype were examined, using a newly-established resistant cell line. Phorbol ester induced morphological changes, ERK activation, calcium-dependent activation of the c-Jun N-terminal kinase (JNK), interleukin-2 synthesis, and growth inhibition in sensitive but not resistant cells. A series of protein kinase C activators caused membrane translocation of protein kinase C's (PKCs) alpha, eta, and theta in both cell lines. While PKC eta was expressed at higher levels in sensitive than in resistant cells, overexpression of PKC eta did not restore phorbol ester-induced ERK activation to resistant cells. In sensitive cells, PKC activators had similar effects on cell viability and ERK activation, but differed in their abilities to induce JNK activation and interleukin-2 synthesis. PD 098059, an inhibitor of the mitogen activated protein (MAP)/ERK kinase kinase MEK, partially inhibited ERK activation and completely blocked phorbol ester-induced cell death in sensitive cells. Thus MEK and/or ERK activation, but not JNK activation or interleukin-2 synthesis, appears to be required for phorbol ester-induced toxicity. Alterations in phorbol ester response pathways, rather than altered expression of PKC isoforms, appear to confer phorbol ester resistance to EL4 cells.      

高效液相色谱法测定消痰咳片的含量

目的：采用反相色谱法同时测定消痰咳片中两种主要成分甲氧苄啶和磺胺体的含量。方法：以乙腈：0.1%H3PO4(15:85)为流动相，检测波长254nm，HPLC法测定含量。结果：试验表明，甲氧苄啶和磺胺林在0.8-8ug范围内呈良好的线性关系，回归方程分别为Y＝－1127.1＋110.2x(r=0.9994),Y=-1852.3 256.2x(r=0.9996),相对标准偏差分别为2.1%和0.8%。结论：该方法简便、准确、可靠。     

丁公藤碱Ⅱ类似物的合成及其生物活性

本文设计合成了丁公藤碱Ⅱ的C_2脱氧和C_8电子等排类似物。药理结果表明,丁公藤碱Ⅱ的C_2羟基是保持其缩瞳活性的关键部分之一;目的物2和4各自分别具有拟和抗胆碱活性;电子等排目的物16和17既无拟也无抗胆碱作用。     

Progressive platelet activation with storage: evidence for shortened survival of activated platelets after transfusion

Platelets are known to become activated during storage, but it is unclear whether such activation affects recovery or survival after platelet concentrate (PC) transfusion. With the use of flow cytometry to determine the percentage of platelets expressing the alpha-granule membrane protein 140 (GMP-140), a known adhesive ligand appearing on the platelet surface after activation, several studies were conducted. These investigations evaluated 1) the occurrence of significant platelet activation over time in PCs (n = 46) stored under standard blood bank conditions; 2) the correlation between platelet activation and platelet recovery in normal subjects after PC storage (n = 12), as assessed by the recovery of Indium-labeled platelets; and 3) the recovery of activated and unactivated platelets in thrombocytopenic cancer patients transfused with standard PCs (n = 11). It was determined 1) that an increasing duration of storage of PC was associated with increasing platelet activation as measured by the percentage of platelets expressing GMP-140, progressing from a mean of 4 +/- 2 percent (SD) on the day of collection to a mean of 25 +/- 8 percent by 5 days of storage: 2) that, in normal subjects, posttransfusion recovery of autologous platelets stored for 2 to 4 days and then labeled with In111 was inversely correlated with the percentage of activated platelets in the transfused PC (r = -0.55, p = 0.05); and 3) that, when thrombocytopenic patients were transfused with standard PCs, the recovery of the activated platelets in the transfused PCs averaged only 38 +/- 15 percent of the number predicted by the absolute platelet increment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Incidence and predictors of acute kidney injury in an urban cohort of subjects with HIV and hepatitis C virus coinfection

Coinfection with hepatitis C (HCV) significantly increases the risk of acute and chronic renal disease in HIV-infected individuals. However, the burden of acute kidney injury (AKI) directly attributable to HIV among HCV-infected individuals and associated risk factors are not well understood. Within a prospective cohort, AKI episodes were identified by a rise in creatinine of 0.5 mg/dL. Incidence of first AKI events was calculated for HIV/HCV coinfected versus HCV monoinfected subjects, and multivariable analyses using Cox proportional hazards were performed to identify predictors of AKI. Throughout the study period, 35% HIV/HCV coinfected and 17% HCV monoinfected subjects developed AKI, with incidence of 8.74/100 person-years and 3.53/100 person-years, respectively (hazard ratio (HR) 2.48; [95% confidence interval (CI) 1.50, 3.74]). In multivariable analysis, HIV coinfection (HR 2.19 [1.33, 3.62]), decompensated cirrhosis (HR 6.64 [3.81, 11.6]), and cocaine use (HR 2.06 [1.15, 3.71]) were independently associated with AKI. HCV genotype, HCV viral load, hazardous drinking, and heroin use were not associated with AKI. Study limitations included potential misclassification bias of HCV-infected individuals as serial HIV antibody testing was not routinely performed after study entry, and inability to adjust for tenofovir use in multivariable analysis. In conclusion, among subjects with HCV infection, decompensated cirrhosis, HIV coinfection, and cocaine use are associated with increased risk of AKI. These findings highlight the importance of preventing and treating cirrhosis, controlling HIV coinfection, and reducing cocaine use in HIV/HCV coinfected persons.     

Multichannel biomagnetic system for study of electrical activity in the brain and heart

The authors designed a multichannel system for noninvasive measurement of the extremely weak magnetic fields generated by the brain and the heart. It uses a flat array of 37 superconducting magnetic field-sensing coils connected to sophisticated superconducting quantum interference devices. To prevent interference from external electromagnetic fields, the system is operated inside a shielded room. Complete sets of coherent data, even from spontaneous events, can be recorded. System performance was evaluated with phantom measurements and evoked-response studies. A spatial resolution of a few millimeters and a temporal resolution of a millisecond were obtained. First results in patients with partial epilepsy and investigations of the cardiac conductive pathway indicate that biomagnetism is now ready for a systematic clinical evaluation. Interpretation of measurements was facilitated by highlighting biomagnetically localized electrical activity in three-dimensional digital magnetic resonance images.     

Comorbidity,limitations in activities and pain in patients with osteoarthritis of the hip or knee

Background  

This study aims to contribute to the knowledge of the influence of comorbidity in OA. The objectives of the study were (i) to describe the prevalence of comorbidity and (ii) to describe the relationship between comorbidity (morbidity count, severity and the presence of specific diseases) and limitations in activities and pain in elderly patients with knee or hip OA using a comprehensive inventory of comorbidity.     

The Treatment of Septicemia in Pacemaker Patients

The authors analyzed the data of seven patients who had undergone open heart surgery because of pacemaker endocarditis in the past 4 years. Repeated surgical interventions on the pacemaker system were found to be the most common predisposing factors. Staphylococcus aureus and Staphylococcus epidermidis were the most common causative organisms. Two-dimensional echocardiography was important in the diagnosis of cases with atypical clinical picture and negative blood cultures. We concluded that: (1) any pacemaker patient with fever should be considered to have a pacemaker endocarditis; (2) all of these patients should be examined by two-dimenensional echocardiography; and (3) the total removal of the infected hardware seems to be the only way to achieve complete recovery.     

Incorporation of the fluoroless C-Arm Trainer at the American Urological Association hands on training percutaneous renal access

Objectives

To assess for usefulness and validity evidence for incorporating the C-Arm Trainer (CAT) simulator into the annual AUA hands on course for training percutaneous nephrolithotomy (PCNL).

Materials and methods

The course started with a didactic session followed by four stations for training the “bull’s eye” technique using the CAT simulator. Each station included a pre-test, 30-min practice on the simulator, and post-test. All participants were assessed using a 4-item checklist. All participants were asked to fill in a qualitative self-assessment questionnaire after the pre- and the post-test, and respond to a course evaluation questionnaire and post-course survey.

Results

A total of 38 physicians, who attended the hands on course, voluntarily participated in the study. Only 21.1% had previous practice on PCNL simulators. Compared with the results of the checklist total score and the qualitative self-assessment questionnaire scores after the pre-test, there was significant improvement in the checklist total score (p < 0.001), temporal demands (p = 0.003), situational stress (p = 0.003, and performance (0.003) after the post-test. A total of 14 (36%) participants responded to the course evaluation questionnaire, 50% evaluated the course as excellent, 28.6% as very good, and 21.4% as good. Unfortunately, only five (13%) participants responded to the post-course survey, 4/5 implemented the new competencies and knowledge into their practice, and 3/5 have attempted to obtain fluoroscopic guided PCA without assistance.

Conclusion

The CAT simulator was considered useful for training the percutaneous renal access procedure. There was significant improvement in the qualitative and quantitative assessment parameters after the post-test compared with the pre-test.