Assessment of CMV load in solid organ transplant recipients by pp65 antigenemia and real-time quantitative DNA PCR assay: correlation with pp67 RNA detection

After bone marrow (BM) or solid-organ (SO) transplantation viremic Cytomegalovirus (CMV) infection is observed frequently. Quantitative assay of CMV in blood helps the management of this clinical condition. In the present report, 83 samples from 39 solid organ recipients, three CMV assays were compared simultaneously for the first time: the Nuclisens CMV pp67 assay (nucleic acid sequence-based amplification, NASBA), an "in-house" quantitative real-time PCR assay (TaqMan) for CMV DNA, and pp65 antigenemia. The relation between CMV DNA and pp65 antigenemia, the quantitative assays, was evaluated on a larger group including 251 blood samples from 118 solid organ recipients. Real-time PCR provided the best results; > or =130 CMV DNA copies/2 x 10(5) peripheral blood leukocytes (PBLs) predicted > or =1 pp65 antigen positive (Ag+) cell/2 x 10(5) PBLs. By taking pp65 antigenemia as the "gold standard," the sensitivity of CMV DNA quantitation and of the pp67 RNA assay were 0.95 and 0.20, respectively, while the corresponding specificity values were 0.50 and 0.93. When real-time PCR was considered as the "gold standard," the sensitivity and specificity of the pp65 antigenemia were 0.65 and 0.91, respectively. Among the three tests examined, the sensitivity of the pp67 RNA assay was the lowest. On the other hand, the pp67 RNA assay was highly specific and effective in pinpointing high viremia patients. The present report, by providing predictive values for all three diagnostic profiles, DNA load, antigenemia, and pp67RNA, is a contribution for validation of real-time PCR as a new standard for quantitative assessment of CMV viremia in clinical settings.     

PAN-811 provides neuroprotection against glutamate toxicity by suppressing activation of JNK and p38 MAPK

In an earlier study, we demonstrated that PAN-811 (3-aminopyridine-2-carboxaldehyde thiosemicarbazone), a novel neuroprotectant, provides protection against glutamate, staurosporine, veratridine, or hypoxia/hypoglycemia toxicities in primary cortical neuronal cultures by upregulating Bcl-2 expression [R.-W. Chen, C. Yao, X.C. Lu, Z.-G. Jiang, R. Whipple, Z. Liao, H.A. Ghanbari, B. Almassian, F.C. Tortella, J.R. Dave. PAN-811 (3-aminopyridine-2-carboxaldehyde thiosemicarbazone), a novel neuroprotectant, elicits its function in primary neuronal cultures by upregulating Bcl-2 expression. Neuroscience 135 (2005) 191–201]. Both JNK (c-Jun N-terminal kinase) and p38 MAP (mitogen-activated protein) kinase activation have a direct inhibitory action on Bcl-2 by phosphorylation. In the present study, we continued to explore the mechanism of PAN-811 neuroprotection. Our results indicate that treatment of cultured cortical neurons with glutamate (100 μM) induces phosphorylation of both JNK and p38 MAPK. Specifically, pretreatment of neurons with 10 μM PAN-811 (an optimal neuroprotective concentration) for 1 h, 4 h, or 24 h significantly suppresses glutamate-mediated activation of both JNK and p38 MAPK. Furthermore, the p38 MAPK-specific inhibitor SB203580 and the JNK-specific inhibitor SP600125 prevented glutamate-induced neuronal death in these primary cultures. Our results demonstrate that glutamate-induced phosphorylation of JNK and p38 MAPK is suppressed by PAN-811, which might contribute to Bcl-2 upregulation and PAN-811 neuroprotection.     

Macrophage-tumour cell interactions: identification of MUC1 on breast cancer cells as a potential counter-receptor for the macrophage-restricted receptor, sialoadhesin

In many carcinomas, infiltrating macrophages are commonly found closely associated with tumour cells but little is known concerning the nature or significance of adhesion molecules involved in these cellular interactions. Here we demonstrate in primary human breast cancers that sialoadhesin (Sn), a macrophage-restricted adhesion molecule, is frequently expressed on infiltrating cells that often make close contact with breast carcinoma cells. To determine whether Sn could act as a specific receptor for ligands on breast cancer cell lines, binding assays were performed with a recombinant form of the protein fused to the Fc portion of human immunoglobulin G1 (IgG1) (Sn-Fc). Sn-Fc was found to bind specifically and in a sialic acid-dependent manner to the breast cancer cell lines MCF-7, T47.D and BT-20 both in solid- and solution-phase binding assays. To investigate the nature of the sialoglycoproteins recognized by Sn on breast cancer cells, MCF-7 cells were labelled with [6-3H]glucosamine. Following precipitation with Sn-Fc, a major band of approximately 240000 MW was revealed, which was shown in reprecipitation and Western blotting experiments to be the epithelial mucin, MUC1.     

Modification of electron-beam dose distributions by transverse magnetic fields

By applying a transverse magnetic field to a dosimetry phantom, an incident high-energy electron beam is made to follow a spiral path in the course of slowing down. Certain levels, determined by the electron energy and the magnetic field strength, will be traversed several times by the same electrons. The net result of this process is an enhancement of the depth dose in relation to the entrance dose, and a more sharply defined depth of penetration. Experiments with 50- and 55-MeV electrons traversing a 20.5-kG field are shown to support the predictions of a detailed Monte Carlo calculation.     

The surface measurement of aortic atherosclerosis: critical survey and comparison with histologic findings

Both the reproducibility of the surface measurements of aortic atherosclerosis and the agreement between gross inspective and histologic changes were evaluated. Aortas from male broad breasted white turkeys were chosen because of the high incidence of spontaneous and typical atherosclerotic lesions in this animal strain. Ten male turkeys were killed at 33 weeks of age. The aortas were removed including the iliac bifurcation and stained with Sudan III. Each aorta was processed blindly by four pathologists and a computerized planimeter to determine normal areas, sudanophilic areas and areas covered by plaques. The analysis of variance showed significant differences among the four pathologists' measurements of sudanophilic areas (P less than 0.01) and areas covered by plaques (P less than 0.001). The coefficients of variation among the four determinations made by one pathologist on the same aorta were 3.6% for total aortic area; 10.08% for sudanophilic area; 47.6% for the area covered by plaques. On each aorta histology was performed at the level where all the four pathologists recorded the same findings at inspection, namely a normal area, a sudanophilic area, and an area covered by plaques. Important discrepancies occurred between findings at inspection and those of histologic examination: the ten areas classified as "normal" by all the four pathologists at inspection were shown at histologic examination to be normal in only two cases. In one case a musculo-elastic layer and in seven cases a fibro-elastic layer were found. The ten areas classified as "sudanophilic" by all the observers showed a fibro-elastic layer in five cases, a musculo-elastic layer in two cases and normal findings in three cases. The ten areas classified as "covered by plaques" displayed a typical atherosclerotic plaque in all cases but one. In conclusion, our data indicate that the reproducibility of gross inspective methods is low. Important discrepancies exist between findings at inspection and histologic examinations. The relevance of these findings remains to be established as far as the assessment of human atherosclerosis is concerned.     

Left ventricular regional function in patients with dilated cardiomyopathy (computerized echocardiographic data)

Computerized echography was used to assess left-ventricular dysfunction in 40 patients with dilatation cardiomyopathy (DCM). The so-called "floating" system was shown to be the most acceptable model for the correction of DCM-associated superposition. An original system was used for segment division by two- and four-chamber projections. Total left-ventricular hypokinesia and a significant reduction of the total ejection fraction (32.5 +/- 1.9%) were demonstrated.     

Community Based Assessment of Unintentional Injuries in a Community Development Block of Purba Bardhaman District,West

BackgroundInjuries are a focus of public health practice because they pose a serious health threat and are preventable. Currently, injury accounts for 14% of all Disability Adjusted Life Years (DALYs) losses for the world''s entire population. In India, unintentional injuries within the home environment have not so far been recognized to the same extent as traffic and work-related injuries among all age groups. With this background, a community based epidemiological study was conducted with the aim to find out the prevalence and epidemiology of unintentional injuries.MethodsA cross-sectional study was conducted during July 2018 - June 2019 in Bhatar block of Purba Bardhaman District. Cluster random sampling was applied to select required sample of 555 individuals from 24 villages. The study tools used were a predesigned and pretested schedule developed by the researchers with the help of Guidelines for conducting community surveys on injuries by World Health Organization (WHO) and a checklist for assessing household level injury hazard. The study had approval from Institutional Ethics Committee. Chi square test and multivariable logistic regression were performed using SPSS V16.ResultsPrevalence of unintentional injury was 8.8 % in the preceding three months. Multivariable logistic regression revealed that those who were below 18 years of age, severely vulnerable to unintentional injuries and belonged to nuclear families had significantly higher odds of developing unintentional injuries at home.ConclusionUnintentional injury is prevalent in West Bengal. Dissemination of injury prevention information with special focus on household modification is an effective strategy to prevent unintentional injuries.     

Efficacy and Safety of Atezolizumab Plus Bevacizumab Following Disease Progression on Atezolizumab or Sunitinib Monotherapy in Patients with Metastatic Renal Cell Carcinoma in IMmotion150: A Randomized Phase 2 Clinical Trial

BackgroundThe use of immune checkpoint inhibitors combined with vascular endothelial growth factor (VEGF)-targeted therapy as second-line treatment for metastatic clear cell renal cancer (mRCC) has not been evaluated prospectively.ObjectiveTo evaluate the efficacy and safety of atezolizumab + bevacizumab following disease progression on atezolizumab or sunitinib monotherapy in patients with mRCC.Design, setting, and participantsIMmotion150 was a multicenter, randomized, open-label, phase 2 study of patients with untreated mRCC. Patients randomized to the atezolizumab or sunitinib arm who had investigator-assessed progression as per RECIST 1.1 could be treated with second-line atezolizumab + bevacizumab.InterventionPatients received atezolizumab 1200 mg intravenously (IV) plus bevacizumab 15 mg/kg IV every 3 wk following disease progression on either atezolizumab or sunitinib monotherapy.Outcome measurements and statistical analysisThe secondary endpoints analyzed during the second-line part of IMmotion150 included objective response rate (ORR), progression-free survival (PFS), and safety. PFS was examined using Kaplan-Meier methods.Results and limitationsFifty-nine patients in the atezolizumab arm and 78 in the sunitinib arm were eligible, and 103 initiated second-line atezolizumab + bevacizumab (atezolizumab arm, n = 44; sunitinib arm, n = 59). ORR (95% confidence interval [CI]) was 27% (19–37%). The median PFS (95% CI) from the start of second line was 8.7 (5.6–13.7) mo. The median event follow-up duration was 19.4 (12.9–21.9) mo among the 25 patients without a PFS event. Eighty-six (83%) patients had treatment-related adverse events; 31 of 103 (30%) had grade 3/4 events. Limitations were the small sample size and selection for progressors.ConclusionsThe atezolizumab + bevacizumab combination had activity and was tolerable in patients with progression on atezolizumab or sunitinib. Further studies are needed to investigate sequencing strategies in mRCC.Patient summaryPatients with advanced kidney cancer whose disease had worsened during treatment with atezolizumab or sunitinib began second-line treatment with atezolizumab + bevacizumab. Tumors shrank in more than one-quarter of patients treated with this combination, and side effects were manageable.