Relationship of nm23 to proteolytic factors, proliferation and motility in breast cancer tissues and cell lines.

Low expression of the antimetastatic gene nm23 has been associated with shorter overall survival in breast cancer. To better understand the mechanism(s) of action of this protein, we compared the levels of the nm23 protein in 152 breast cancer samples with other factors known to be involved in metastasis or related to prognosis. There was no significant relationship between either of the nm23 isoforms and cathepsin D (Cat-D), urokinase plasminogen activator (uPA), its inhibitor (PAI-1), steroid hormone receptors or ploidy status. A marginal inverse correlation was observed between per cent S-phase and nm23-H1 expression (r = -0.193, P = 0.047) and a positive correlation was observed between uPA receptor (uPAR) and both nm23-H1 (r = 0.263, P = 0.0018) and nm23-H2 (r = 0.230, P = 0.0064). The nm23-H1 gene was transfected into MDA-MB-231 human breast cancer cells and 12 clones were selected, of which two were characterized extensively. We found no significant differences in Cat-D, uPA, PAI-1 or uPAR, as a function of nm23 expression in either the MDA-MB-231 cells or the transfected clones. Compared with the parent cell line, we did observe a dose-dependent decrease in growth factor-stimulated motility and a decrease in metastatic potential in two clones with four- and eightfold elevated nm23-H1 expression, whereas the proliferative activities were similar. We conclude that the decreased metastatic potential might be related to down-regulation of growth factor-stimulated motility.     

Human chondrocyte expression of growth-arrest-specific gene 6 and the tyrosine kinase receptor axl. Potential role in autocrine signaling in cartilage

Objective. To determine if human articular chondrocytes express the axl tyrosine kinase receptor and its ligand Gas-6, a protein product of growth-arrest-specific gene 6, and to determine if Gas-6 and axl function in the regulation of chondrocyte growth and survival. Methods. The presence of Gas-6 and axl was examined in situ in human articular cartilage by immunohistochemistry and in vitro in cell culture studies using primary human chondrocytes and immortalized human chondrocytes. The ability of recombinant Gas-6 to mediate adhesion of chondrocytes and to stimulate chondrocyte axl phosphorylation was determined. Studies of the role of Gas-6 and axl in cell proliferation and survival were also performed. Results. Both Gas-6 and axl were detected in cartilage by immunohistochemical staining. Gas-6 and axl messenger RNA (mRNA) and protein were also detected in cultures of primary and immortalized human chondrocytes. Compared with cells cultured in medium containing 10% serum, Gas-6 mRNA levels were increased in immortalized chondrocytes cultured in serum-free medium, while axl expression decreased. Chondrocytes attached to Gas-6-coated plastic, and the attachment was blocked by a soluble Ig fusion protein containing the axl extracellular domain. Recombinant human Gas-6 and serum-free conditioned medium from primary and immortalized human chondrocyte cultures stimulated chondrocyte axl tyrosine phosphorylation. A mitogenic effect was noted both when immortalized chondrocytes were stimulated with recombinant Gas-6 or when they were made to overexpress axl by transfection. Addition of recombinant Gas-6 to serum-free medium resulted in increased survival of primary chondrocytes cultured at low density in agarose. Conclusion. These findings present evidence for an autocrine signaling pathway in cartilage involving Gas-6 and the axl tyrosine kinase adhesion receptor. Stimulation of axl by Gas-6 may play an important role in the control of chondrocyte growth and survival.     

Prevalence and predictors of renal artery stenosis in patients undergoing peripheral and coronary angiography

Background

Renal artery stenosis is a potential cause of secondary hypertension, ischemic nephropathy and end-stage renal disease. Atherosclerosis is by far the most common etiology of renal artery stenosis in elderly. We investigated whether the presence of significant atherosclerotic renal artery stenosis (ARAS) with luminal diameter narrowing ≥50 % could be predicted in patients undergoing peripheral and coronary angiography.

Methods

The records of 3,500 consecutive patients undergoing simultaneous renal angiography along with peripheral and coronary angiography were reviewed. The patients with known renal artery disease were excluded.

Results

Prevalence of ARAS was 5.7 %. Significant ARAS (luminal diameter narrowing ≥50 %) was present in 139 patients (3.9 %). Hypertension with altered serum creatinine and triple-vessel CAD were associated with significant renal artery stenosis in multivariate analysis. No significant relationship between the involved coronary arteries like left anterior descending, left circumflex, right coronary artery and ARAS was found. Only hypertension and altered serum creatinine were associated with bilateral ARAS. Extent of CAD or risk factors like diabetes, hyperlipidemia or smoking did not predict the unilateral or bilateral ARAS.

Conclusion

Prevalence of ARAS among the patients in routine cardiac catheterization was 5.7 %. Hypertension is closely associated with significant ARAS. Significant CAD in the form of triple-vessel disease and altered renal function tests are closely associated with ARAS. They predict the presence of significant renal artery stenosis in patients undergoing routine peripheral and coronary angiography. Moreover, hypertension and altered renal functions predict bilateral ARAS.     

Expanding donor pool by utilizing deceased donors with snake envenoming

In India, the deceased kidney transplant program is still in its preliminary stage, and accepting deceased donors with snakebite is just a forward step to expand the donor pool. We report here the outcome of 8 successful renal transplantations from brain-dead donors who died from a neurotoxic snakebite. We accepted them as donors as they had no evidence of hemotoxic snakebite. 7 recipients did well. 1 died due to sepsis with a functioning graft. 1 required renal biopsy that showed acute tubular necrosis. 1 required re-exploration due to graft collection due to a surgical issue. Patient and graft survival in follow-up were similar to other matched deceased donors in our center. According to our experience, utilizing brain-dead donors who died from a neurotoxic snakebite is safe and may dramatically expand the donor pool especially in countries where death due to snakebite is high in numbers.     

Inhibition of DNA Synthesis by a Platinum-Acridine Hybrid Agent Leads to Potent Cell Kill in Non-Small Cell Lung Cancer

The platinum-acridine anti-cancer agent [PtCl(en)(LH)](NO(3))(2) (1) (en = ethane-1,2-diamine, LH = N-(2-(acridin-9-ylamino)ethyl)-N-methylpropionimidamide, acridinium cation) and the clinical drug cisplatin were studied in chemoresistant non-small cell lung cancer (NSCLC) cell lines for their cytotoxic potency and cell-kill mechanisms. In the three cell lines tested (NCI-H460, NCI-H522, and NCI-H1435) compound 1 shows a pronounced cytotoxic enhancement of 40-200-fold compared to cisplatin at inhibitory concentrations reaching the low-nanomolar range. Based on changes in cell adhesion and cell morphology, monitored in real time by impedance measurements, compound 1 kills NCI-H460 cells significantly more efficiently than cisplatin at equitoxic concentrations. Flow cytometry analysis of NCI-H460 cells reveals a robust S-phase arrest of cells treated with compound 1, whereas cells treated with cisplatin progress to G2/M of the cell cycle. A pronounced inhibition of DNA replication in 75% of viable cells is observed in NCI-H460 cells treated with compound 1 at an IC(90) molar concentration for 48 h, based on the reduced incorporation of the fluorophore-clickable nucleoside analogue 5-ethynyl-2′-deoxyuridine (EdU) into newly synthesized DNA. The distinct cell-cycle perturbations and cell-kill potential of compound 1 are discussed in the light of the DNA interactions of this agent and its potential to overcome cisplatin resistance in NSCLC.     

Comparative evaluation of bioglass with calcium sulphate β-hemihydrate for the treatment of intraosseous defects—a clinico-radiological study

Background

The aim of the present clinical and radiological study was to compare bioglass and calcium sulphate β-hemihydrate in the treatment of intraosseous defect in chronic periodontitis.

Method

A total of 50 subjects with bilaterally symmetrical periodontal osseous defects with probing pocket depth = 5 mm and intraosseous defects ≥ 3 mm as seen on the radiographs were undertaken for the study. In one site (group A) bioactive glass was placed in defect and in contralateral site (group B) calcium sulphate β-hemihydrate was used in the defect site.

Results

Clinical improvement was noted in all patients at the end of study. Both the groups showed reduction in probing pocket depth, increase in clinical attachment level, and reduction in osseous defect. Both materials were effective in achieving osseous gain.

Conclusion

The osseous gain in group A subjects was 58.93%, whereas in group B subjects it was 48.56%. Calcium sulphate β-hemihydrates showed promising results and were cost effective.Key Words: bone grafts, periodontal osseous defects     

Mesenchymal stem cells and transplant tolerance

Different strategies are being tried to induce transplant tolerance in clinical settings; however, none of them are both safe and effective. Mesenchymal stem cells have been found to be potent immunomodulators and immunosuppressants. We discuss in this review different sources of mesenchymal stem cells and the potent role of adipose tissue‐derived mesenchymal stem cells in induction of transplant tolerance including when to use them and how to use them for achieving the Utopian dream of transplant tolerance.     

Patient perception of wound photography

The objectives of this study were to provide an assessment of photographic documentation of the wound from the patients' perspective and to evaluate whether this could improve patients' understanding of and involvement in their wound care. Our results revealed that most patients visiting the wound care clinic have difficult‐to‐see wounds (86%). Only 20% of patients monitor their wounds and instead rely on clinic or nurse visits to track the healing progress. There was a significant association between patients' ability to see their wound and their subsequent memory of the wound's appearance. This was especially true for patients who had recently begun visiting the wound care clinic. This relationship was not present in patients who had visited the clinic for 3 or more years. Patients reported that the inability to see their wounds resulted in feeling a loss of autonomy. The majority of patients reported that photographing their wounds would help them to track the wound progress (81%) and would afford them more involvement in their own care (58%). This study provides a current representation of wound photography from the patients' perspective and reveals that it can motivate patients to become more involved in the management of their wounds – particularly for patients with difficult‐to‐see wounds.