Platelet-melanoma cell interaction is mediated by the glycoprotein IIb- IIIa complex

A human malignant melanoma cell line (M3Dau) was observed by electron microscopy to interact directly with human platelets and induced platelet aggregation. Fab fragments of a monoclonal antibody MoAb (LYP18), directed against the platelet glycoprotein (GP) IIb-IIIa complex, inhibited platelet-melanoma interactions and platelet-platelet aggregation. M3Dau melanoma cells bind LYP 18 and synthesize IIb-IIIa- like GPs. When the melanoma cells were preincubated with LYP 18, tumor- platelet interaction did not occur, suggesting that the interaction may be mediated by the IIb-IIIa-like GPs present on the melanoma cell surface. Glanzmann's thrombasthenic platelets, lacking GPIIb and IIIa, did not interact with melanoma cells, indicating that the platelet GPIIb-IIIa complex is also necessary for the platelet-melanoma cell interaction. This work demonstrates the importance of the IIb-IIIa-like GPs, present on M3Dau melanoma cells, in mediating tumor-platelet interactions.     

AH23848: a thromboxane receptor-blocking drug that can clarify the pathophysiologic role of thromboxane A2

Despite numerous suggestions in the literature that thromboxane A2 is involved in a variety of occlusive vascular diseases, no definitive evidence is available. Arguments have been presented to support the view that such evidence can only come from clinical studies with a highly specific thromboxane receptor-blocking drug. We have now identified such a drug, AH23848, in our laboratories. Preliminary experiments with AH23848, ([1 alpha (Z), 2 beta,5 alpha]-(+/-)-7-[5-[[(1,1'-biphenyl)-4-yl]methoxy]-2-(4-morpholin yl)-3-oxocyclopentyl]-4-heptenoic acid), show that it is a potent, specific thromboxane receptor-blocking drug that is orally active and has a long duration of action. It should be a valuable tool in elucidating any physiologic or pathologic role of thromboxane A2.     

Lung biopsy for chronic pulmonary disease in children

Introduction and objectives

Lung biopsy is frequently used in the management of children with chronic pulmonary disease to obtain a histological diagnosis. We further evaluate the role of lung biopsy by reviewing our experience of this procedure.

Methods

A retrospective case-note review was carried out of all patients in our regional service under 16 years who underwent a lung biopsy from 1998 to 2011.

Results

Thirty-three children (12 boys) (median 5 years 5 months, range 2 months to 16 years) underwent lung biopsy in the period studied. Following the procedure, 17 patients required ventilation on the intensive care unit for a median of two days (range 1–56 days). Complication rate was 30% (10/33); seven simple pneumothoraces, one tension pneumothorax, and one pneumonia (one child experienced more than one complication). The operative mortality was 12% (4/33). Three children (9%) died within 28 days of surgery. Twenty-six (79%) biopsies provided a definitive histological diagnosis. In 16 (48%) children, the working diagnosis and treatment were changed following lung biopsy.

Conclusion

Lung biopsy has an important role in the management of children with chronic pulmonary disease. However, it carries significant risks which must be considered when assessing the need for histological diagnosis.     

Vascular Compromise from Soft Tissue Augmentation: Experience with 12 Cases and Recommendations for Optimal Outcomes

The popularity of soft tissue fillers is, in part, due to their favorable side-effect profile. However, serious complications can occur. The authors describe their extensive clinical experience with soft-tissue augmentation and the rare complication of vascular compromise, which can lead to necrosis and scarring. Over a 10-year period between January 2003 and January 2013, the authors observed a total of 12 cases of vascular compromise. Eight patients in their clinical practice showed evidence of vascular compromise out of a total of 14,355 filler injections (0.05%). In addition, four patients treated with an experimental particulate filler had vascular complications. All cases were examined for filler type, location of complication, risk factors, treatment, and outcomes. Although treatment plans differed for each patient in their series, all cases of vascular compromise resolved fully. The authors believe that an office-based protocol for both immediate and ongoing care—including a thorough individualized assessment and treatment plan for each patient—is critical to timely and effective resolution of side effects. They propose key recommendations for the prevention and management of vascular compromise to improve patient outcomes and reduce the risk of permanent complications.Injectable fillers have become an integral part of aesthetic medicine for patients who want noninvasive rejuvenation. They are used to restore volume and to smooth and efface superficial wrinkles and deep folds of the face, among other indications. Widespread use began in the 1980s with the advent of bovine collagen. Since then, use has surged so that soft tissue augmentation is the second most popular nonsurgical aesthetic procedure in North America to botulinum toxin.1 In 2007, more than 1.5 million soft tissue filler procedures were performed in the United States, with hyaluronic acid (HA) being the most frequently used.2 As of 2010, more than 200 types of fillers were available for soft tissue augmentation worldwide.1The popularity of soft tissue fillers is in part due to their favorable side-effect profile. Adverse effects from soft tissue filler injection are generally mild and self-limited. However, there are some well-documented serious complications. The most feared and potentially serious complications are vascular in nature. Collectively referred to as vascular compromise, these complications include partial or complete interruption of vascular supply by extravascular compression, or a complete occlusion of vascular supply from intravascular injection. Subsequent necrosis and scarring are potentially permanent sequelae.2-4In the authors’ clinical practice, 14,355 filler injections were performed between January 2003, when they first instituted their computer database, and January 2013. Fillers that are used in their office include hyaluronic acid (HA) (Juv''derm Ultra, Ultra plus, Voluma [Allergan, Irvine, California] and Restylane [Medicis Aesthetics Inc., Scottsdale, Arizona]); poly-L-lactic acid (Sculptra, Sanofi-Aventis, Bridgewater, New Jersey); calcium hydroxylapatite (Radiesse, Merz USA, Greensboro, North Carolina); silicone oil; and collagen (Evolence Breeze, Ortho Dermatologics, Skillman, New Jersey). During this 10-year period, a total of 12 cases of vascular compromise were observed and managed, eight of which occurred in the authors’ clinical practice and four in their clinical trials practice. Those cases that developed vascular compromise after soft tissue augmentation are reviewed and treatment discussed (Appendix 1).Over a 10-year period between January 2003 and January 2013, eight patients in the authors'' clinical practice showed evidence of vascular compromise out of a total of 14,355 filler injections (0.05%). They observed four cases after injection with calcium hydroxylapatite (CaHA) (out of 1,482 total injections; 0.27%), four cases after injection with volumizing monophasic HA (Juvéderm Voluma) (out of 4,321 total injections; 0.09%), and one case resulting from treatment with biphasic HA (Restylane) (out of 3,348 injections; 0.03%). One patient was treated with both CaHA and volumizing monophasic HA, and is counted in both groups (

Progress in understanding oral health and HIV/AIDS

Over the last 30 years, there have been significant advances in our scientific knowledge of HIV disease, including prevention, detection, medical management, and attempts at cure. Investigations and observations of the oral cavity in individuals with HIV disease have contributed substantially to scientific discovery and innovation. Challenges remain for managing existing and emerging oral diseases associated with HIV and understanding the contribution of latent oral mucosal reservoirs to HIV eradication.     

Influence of inhibitors of ATP catabolism on myocardial recovery after ischemia

The loss of the catabolic products of adenosine triphosphate in the form of purine nucleosides and oxypurines during ischemia and subsequent reperfusion may limit adenine nucleotide regeneration. This study compared the effects of infusion of inhibitors of the major reactions involved in the degradation of adenosine triphosphate to inosine on the postischemic recovery of high energy phosphate and myocardial function. Isolated rat hearts were made totally ischemic after a 5-min infusion of p1,p5-diadenosine pentaphosphate, alpha, beta-methylene adenosine diphosphate, nitrobenzyl-6-thioinosine, or erythro-9-(2-hydroxy-3-nonyl) adenine, which are inhibitors of adenylate kinase, 5'-nucleotidase, adenosine translocase, and adenosine deaminase, respectively. Following 30 min of ischemia, only hearts infused with alpha, beta-methylene adenosine diphosphate recovered significantly better ventricular function than did the control (P less than 0.05), but all hearts had increased adenosine triphosphate and creatine phosphate regeneration (P less than 0.05). The formation and washout of greater than 30% of the total adenine pool metabolites were not prevented by any drug. Nevertheless all manipulations of adenine metabolism resulted in recruitment of high energy phosphate during preischemic infusion which may have potential benefits in elective ischemic arrest.     

Effect of transforming growth factor-beta 1 on proliferation and induction of hemoglobin accumulation in K-562 cells

The effects of transforming growth factor-beta 1 (TGF-beta 1) on proliferation and hemoglobinization in K-562 cells, a human multipotential hematopoietic cell line, were studied. We found that TGF- beta 1 could induce hemoglobin accumulation in K-562 cells. Various clones were selected on the basis of the inducibility of hemoglobinization by TGF-beta 1. One high response clone (no. 1) and one low response clone (no. 8) were studied in detail. Hemoglobin accumulation peaked on day 5 of culture in the presence of TGF-beta 1 (0.5 ng/mL, 20 pmol/L), when 90% of clone 1 cells, 55% of parent line cells, and less than 10% of clone 8 cells contained hemoglobin. There was a concomitant reduction in proliferation of 60% for clone 1, 40% for the parent line, and 30% for the clone 8 on day 5 of culture. Quantitative analysis showed that the hemoglobin contents in clone 1 after 5-day induction by TGF-beta 1 and hemin were 1.0 pg/cell and 2.9 pg/cell, respectively. The hemoglobin induced by TGF-beta 1 showed the same electrophoretic characteristics as the hemoglobin induced by hemin. The expression of epsilon-globin mRNA was minimally detectable in control cells and was induced in both TGF-beta 1 and hemin treated cells. Other cytokines with potential effects on K-562 cell proliferation and differentiation were also studied. Interleukin-1, interleukin-3, interferon alpha, interferon gamma, and inhibin, tested as single agents, showed minimal effects on proliferation. None of these agents could induce hemoglobinization or inhibit the hemoglobinization induced by TGF-beta 1.     

Molecular and phenotypical investigation of ciprofloxacin resistance among Campylobacter jejuni strains of human origin: high prevalence of resistance in Turkey

Campylobacteriosis is one of the most frequently reported zoonoses worldwide. The well-documented increase in the ciprofloxacin resistance has increased the importance of rapid detection of the resistance. The incidence of ciprofloxacin resistance was investigated using real-time PCR. Identification of one hundred and fifty-eight strains was performed by PCR. Minimum inhibitory concentration (MIC) of ciprofloxacin was determined by Epsilometer test. Following the confirmation of the efficiencies of singleplex real-time PCR methods using two different probes, a cytosine to thymine point mutation at codon 86 was detected by allelic discrimination. Of the 158 strains, 114 (72.2%) were determined to be resistant to ciprofloxacin. The MIC₅₀ and the MIC₉₀ of ciprofloxacin were found to be 8 and ≥32 mg/L, respectively. By real-time PCR, the presence of the mutation was confirmed in all, but one, resistant strains and the absence of the mutation was demonstrated in all, but one, susceptible strains. The rate of resistance is high among C. jejuni strains and ciprofloxacin should not be used in the treatment of such infections in Turkey. A cytosine to thymine mutation is the most frequently detected mechanism for the resistance. Real-time PCR can be used for the quick screening of the resistance.