Immunochemical studies of serum, urine and calculus proteins in urolithiasis

Total serum protein levels in 70 patients with urolithiasis were not significantly different from those in 20 control subjects, although certain variations were detected in individual protein patterns. In contrast, total urinary protein was significantly higher in patients with urolithiasis. 4-6 different components, i.e., albumin, alpha 1-acidic glycoprotein, alpha 1-antitrypsin, Gc-globulin, fibrinogen and immunoglobulin G, were found in the matrices of calculi and in urine, suggesting that proteinuria may play a role in the formation of stones in patients with urolithiasis.     

User guide for the discovery of potential drugs via protein structure prediction and ligand docking simulation

Journal of Microbiology - Due to accumulating protein structure information and advances in computational methodologies, it has now become possible to predict protein-compound interactions. In...     

Generation and Characterization of an Immortalized Human Esophageal Myofibroblast Line

Stromal cells with a myofibroblast phenotype present in the normal human esophagus are increased in individuals with gastro-esophageal reflux disease (GERD). We have previously demonstrated that myofibroblasts stimulated with acid and TLR4 agonists increase IL-6 and IL-8 secretion using primary cultures of myofibroblasts established from normal human esophagus. While primary cultures have the advantage of reflecting the in vivo environment, a short life span and unavoidable heterogeneity limits the usefulness of this model in larger scale in vitro cellular signaling studies. The major aim of this paper therefore was to generate a human esophageal myofibroblast line with an extended lifespan. In the work presented here we have generated and characterized an immortalized human esophageal myofibroblast line by transfection with a commercially available GFP-hTERT lentivirus. Immortalized human esophageal myofibroblasts demonstrate phenotypic, genotypic and functional similarity to primary cultures of esophageal myofibroblasts we have previously described. We found that immortalized esophageal myofibroblasts retain myofibroblast spindle-shaped morphology at low and high confluence beyond passage 80, and express α-SMA, vimentin, and CD90 myofibroblast markers. Immortalized human esophageal myofibroblasts also express the putative acid receptor TRPV1 and TLR4 and retain the functional capacity to respond to stimuli encountered in GERD with secretion of IL-6. Finally, immortalized human esophageal myofibroblasts also support the stratified growth of squamous esophageal epithelial cells in 3D organotypic cultures. This newly characterized immortalized human esophageal myofibroblast cell line can be used in future cellular signaling and co-culture studies.     

Sporadic Retinoblastoma and Parental Smoking and Alcohol Consumption before and after Conception: A Report from the Children’s Oncology Group

Background

Retinoblastoma is the most frequent tumor of the eye in children and very little is known about the etiology of non-familial (sporadic) retinoblastoma. In this study we examined whether parental tobacco smoking or alcohol consumption (pre- or post-conception) contribute to the two phenotypes (bilateral or unilateral) of sporadic retinoblastoma.

Methods

Two large multicenter case-control studies identified 488 cases through eye referral centers in the United States and Canada or through the Children’s Oncology Group. Controls (n = 424) were selected from among friends and relatives of cases and matched by age. Risk factor information was obtained via telephone interview. We employed multivariable logistic regression to estimate the effects of parental tobacco smoking and alcohol consumption on retinoblastoma.

Findings

Maternal smoking before and during pregnancy contributed to unilateral retinoblastoma risk in the child: year before pregnancy conditional Odds Ratio (OR), 8.9; 95% confidence interval (CI) 1.5–51, and unconditional OR, 2.4; 95% CI, 1.3–4.7; month before or during pregnancy, conditional OR, 3.3; 95% CI, 0.5–20.8, and unconditional OR, 2.8; 95% CI, 1.1–7.0. No association was found for maternal or paternal alcohol consumption.

Conclusion

The results of this study indicate that maternal active smoking during pregnancy may be a risk factor for sporadic retinoblastoma. Our study supports a role for tobacco exposures in embryonal tumors.     

Moleculer dynamics simulaiton revealed reciever domain of Acinetobacter baumannii BfmR enzyme as the hot spot for future antibiotics designing

Acinetobacter baumannii is an alarming nosocomial pathogen that is resistant to multiple drugs. The pathogen is forefront of scientific attention because of high mortality and morbidity found for its complications in the past decade. As a consequence, identification of novel drug candidates and subsequent designing of novel chemical scaffolds is an imperative need of time. In the present study, we used a recently reported structure of BfmR enzyme and performed structure based virtual screening, MD simulation and binding free energies calculations. MD simulation revealed a profound movement of the best-characterized inhibitor towards the α4-β5-α5 face of the enzyme receiver domain, thus indicating its high affinity for this site compared to phosphorylation. Furthermore, it was observed that the enzyme and enzyme-inhibitor complex have high structure stability with mean RMSD of 1.2 and 1.1 Å, respectively. Binding free energy calculations for the complex unraveled high stability with MMGBSA score of ?26.21?kcal/mol and MMPBSA score of ?1.47?kcal/mol. Van der Waal energy was found highly favorable with value of ?30.25?kcal/mol and dominated significantly the overall binding energy. Furthermore, a novel WaterSwap assay was used to circumvent the limitations of MMGB/PBSA that complements the inhibitor affinity for enzyme active pocket as depicted by the low convergence of Bennett, TI and FEP algorithms. Results yielded from this study will not only give insight into the phenomena of inhibitor movement towards the enzyme receiver domain, but will also provide a useful baseline for designing derivatives with improved biological and pharmacokinetics profiles.

Communicated by Ramaswamy H. Sarma     

Tunable Extraordinary Transmission through a Graphene-Covered Hole Array: an Analytical Equivalent-Circuit Modeling Approach

Plasmonics - We study two-dimensional (2D) hole arrays drilled into a perfect conductor slab covered with a graphene sheet. Such arrays support the extraordinary transmission of electromagnetic...     

Association of immune parameters with clinical outcome in stage III colon cancer: results of Southwest Oncology Group Protocol 9009

Levamisole (LMS), utilized in the adjuvant treatment of patients with stage III colon cancer, is immunomodulatory. To determine whether alterations in immune parameters before, during and after 12 months of 5FU/LMS therapy correlate with disease-free survival, 38 patients enrolled on Southwest Oncology Group (SWOG) protocol 8899 received extensive lymphocyte phenotypic analysis prior to therapy and 3, 6, 12 and 15 months after treatment initiation. The median follow-up of patients is 41 months. Significant increases in the proportion and total number of CD56⁺ natural killer cells were seen, starting at 3 months and continuing until 15 months (P < 0.001). Increases in the total numbers of cells expressing CD25 (interleukin-2 receptor), VLA4 and the combinations of CD4: CD45RA and CD4:CDw29 were not evident during therapy but were seen at 15 months (P < 0.05: CD25, CD4:CDw29, CD4:CD45RA; P < 0.001: VLA4). Low levels of CD8⁺ cells prior to treatment initiation and after 3 months of therapy correlated with early relapse within the first year of 5FU/LMS treatment. Patients who have remained disease-free (n = 22, median follow-up 45 months) demonstrated increases in the total numbers of CD8⁺, CD25⁺, CD56⁺, VLA4⁺, CD4: CDw29 and CD4:CD45RA cells, primarily at 15 months. In contrast, patients who relapsed had decreased numbers of CD8⁺, CD4:CDw29, CD4: CD45RA and VLA4⁺ cells and minimal increases in CD56⁺ and CD25⁺ cells. Statistically significant differences between the late-relapse group and the group remaining disease-free were seen for CD25⁺, CD4: CD45RA and CD4:CDw29 cells at the 15-month assay time (P = 0.0276, P = 0.0349, P = 0.0178 respectively). In conclusion, multiple alterations in lymphocyte phenotype, with increases in the proportion and total number of cells involved in cell-mediated immune responses, were seen during and especially following completion of therapy with 5FU/LMS. Many of these changes are significantly associated with clinical outcome and may be useful for risk stratification of stage III colon cancer patients following completion of adjuvant therapy. Received: 9 July 1999 / Accepted: 11 August 1999     

Anti-integrin as novel drug-discovery targets: potential therapeutic and diagnostic implications

The role of integrin and extracellular matrix proteins in various pathological processes (including angiogenesis, thrombosis, apoptosis and cell migration and proliferation), leading to both acute and chronic disease states (e.g. ocular diseases, metastasis, unstable angina, myocardial infarction, stroke, osteoporosis, a wide range of inflammatory diseases, vascular remodeling and neurodegenerative disorders) has been recently documented. A key success in this field is evident from the potential role of the platelet GPIIb/IIIa (alphaIIbbeta3) integrin in the prevention, treatment and perhaps diagnosis of various thromboembolic disorders. Additionally, progress has been shown in the development of leukocyte alpha4beta1 antagonists for various inflammatory indications and alphav integrin antagonists for angiogenesis and vascular-related disorders. However, the exact modes of action of certain integrin antagonists are still not fully clear. Integrin antagonists in clinical or pre-clinical development are expected to be used as a stand-alone therapy or, better, as an adjunct to other pharmacotherapy, radiotherapy or interventional procedures.