Recurrent Genomic Gains in Preinvasive Lesions as a Biomarker of Risk for Lung Cancer

Lung carcinoma development is accompanied by field changes that may have diagnostic significance. We have previously shown the importance of chromosomal aneusomy in lung cancer progression. Here, we tested whether genomic gains in six specific loci, TP63 on 3q28, EGFR on 7p12, MYC on 8q24, 5p15.2, and centromeric regions for chromosomes 3 (CEP3) and 6 (CEP6), may provide further value in the prediction of lung cancer. Bronchial biopsy specimens were obtained by LIFE bronchoscopy from 70 subjects (27 with prevalent lung cancers and 43 individuals without lung cancer). Twenty six biopsies were read as moderate dysplasia, 21 as severe dysplasia and 23 as carcinoma in situ (CIS). Four-micron paraffin sections were submitted to a 4-target FISH assay (LAVysion, Abbott Molecular) and reprobed for TP63 and CEP 3 sequences. Spot counts were obtained in 30–50 nuclei per specimen for each probe. Increased gene copy number in 4 of the 6 probes was associated with increased risk of being diagnosed with lung cancer both in unadjusted analyses (odds ratio = 11, p<0.05) and adjusted for histology grade (odds ratio = 17, p<0.05). The most informative 4 probes were TP63, MYC, CEP3 and CEP6. The combination of these 4 probes offered a sensitivity of 82% for lung cancer and a specificity of 58%. These results indicate that specific cytogenetic alterations present in preinvasive lung lesions are closely associated with the diagnosis of lung cancer and may therefore have value in assessing lung cancer risk.     

Importance of solid lipid nanoparticles (SLN) in various administration routes and future perspectives

Solid lipid nanoparticles (SLN) have been reported to be an alternative system to emulsions, liposomes, microparticles and their polymeric counterparts for various application routes since the early 1990s due to their advantages. Various research groups have also increasingly focused on improving their stability in body fluids after administration by coating of particles with hydrophilic molecules such as poly(ethylene)glycol (PEG) derivatives. Altering surface characteristics by coating SLN with hydrophilic molecules improves plasma stability and biodistribution, and subsequent bioavailability of drugs entrapped. Their storage stability is also increased. This paper basicly reviews types of SLN, principles of drug loading and models of drug incorporation. The influence of PEG coating on particle size and surface characteristics is discussed followed by alteration in pharmacokinetics and bioavailability of drugs in order to target the site of action via SLN. The future direction of research and clinical implications of SLN is also considered.     

Plant ABC proteins--a unified nomenclature and updated inventory

The ABC superfamily comprises both membrane-bound transporters and soluble proteins involved in a broad range of processes, many of which are of considerable agricultural, biotechnological and medical potential. Completion of the Arabidopsis and rice genome sequences has revealed a particularly large and diverse complement of plant ABC proteins in comparison with other organisms. Forward and reverse genetics, together with heterologous expression, have uncovered many novel roles for plant ABC proteins, but this progress has been accompanied by a confusing proliferation of names for plant ABC genes and their products. A consolidated nomenclature will provide much-needed clarity and a framework for future research.     

A case of myiasis in a patient with psoriasis from Turkey

Myiasis infestations caused by the larvae of flies mostly belonging to Cyclorapha suborders are frequently encountered in Turkey, which is located in the subtropical zone. The skin is a common site for myiasis, and the infestations are likely to develop in infected tissues and poorly attended wounds of the skin.

The case, a 30-year-old male patient, was diagnosed with psoriasis 18 years ago. He had psoriatic scales on his right big toe and was receiving corticosteroid and immunosuppressive drugs.

A total of 11 fly larvae were removed from the infected right first toe of the patient. Structures of the stigmas seen in the cross-sections taken from the final segments of these larvae were examined and determined as Sarcophaga spp. larvae.

Patients with infected tissues should be extremely cautious about their wound hygiene and take required fly control measures especially during summer as flies can find a suitable environment for sustenance.     

An uncommon association of vacterl complex with hypertrophic pyloric stenosis and horseshoe lung

We report a case of VACTERL complex which had concomitant horseshoe lung, laryngeal cleft, and hypertrophic pyloric stenosis, which has not been previously reported.     

Genetic manipulation of glycine decarboxylation

The glycine-serine interconversion, catalysed by glycine decarboxylase and serine hydroxymethyltransferase, is an important reaction of primary metabolism in all organisms including plants, by providing one-carbon units for many biosynthetic reactions. In plants, in addition, it is an integral part of the photorespiratory metabolic pathway and produces large amounts of photorespiratory CO(2) within mitochondria. Although controversial, there is significant evidence that this process, by the relocation of glycine decarboxylase within the leaves from the mesophyll to the bundle-sheath, contributed to the evolution of C(4) photosynthesis. In this review, some aspects of current knowledge about glycine decarboxylase and serine hydroxymethyltransferase and the role of these enzymes in metabolism, about the corresponding genes and their expression as well as about mutants and anti-sense plants related to these genes or processes will be summarized and discussed. From a comparison of the available information about the number and organization of GDC and SHMT genes in the genomes of Arabidopsis thaliana and Oryza sativa it appears that these and, possibly, other genes related to photorespiration, are similarly organized even in only very distantly related angiosperms.     

D-GLYCERATE 3-KINASE, the last unknown enzyme in the photorespiratory cycle in Arabidopsis, belongs to a novel kinase family

D-GLYCERATE 3-KINASE (GLYK; EC 2.7.1.31) catalyzes the concluding reaction of the photorespiratory C2 cycle, an indispensable ancillary metabolic pathway to the photosynthetic C3 cycle that enables land plants to grow in an oxygen-containing atmosphere. Except for GLYK, all other enzymes that contribute to the C2 cycle are known by their primary structures, and the encoding genes have been identified. We have purified and partially sequenced this yet missing enzyme from Arabidopsis thaliana and identified it as a putative kinase-annotated single-copy gene At1g80380. The exclusive catalytic properties of the gene product were confirmed after heterologous expression in Escherichia coli. Arabidopsis T-DNA insertional knockout mutants show no GLYK activity and are not viable in normal air; however, they grow under elevated CO2, providing direct evidence of the obligatory nature of the ultimate step of the C2 cycle. The newly identified GLYK is both structurally and phylogenetically distinct from known glycerate kinases from bacteria and animals. Orthologous enzymes are present in other plants, fungi, and some cyanobacteria. The metabolic context of GLYK activity in fungi and cyanobacteria remains to be investigated.     

Tissue-specific oxidative stress responses in fish exposed to 2,4-D and azinphosmethyl

Species- and tissue-specific defenses against the possibility of oxidative stress and lipid peroxidation were compared in adult fish, Oreochromis niloticus and Cyprinus carpio, exposed to 2,4-dichlorophenoxyacetic acid (2,4-D), azinphosmethyl and their combination for 96 h. Superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase activities were monitored in kidney, brain and gill. In all exposure groups there was a marked increase in SOD activity in gill tissues in both fish species, while it was at the control level in other tissues. The highest elevation of SOD activity by combined treatment was observed in C. carpio. Individual and combined treatments caused an elevation in catalase and GPx activities in kidney of C. carpio. Catalase activity was unaffected in brain of O. niloticus, while GPx activity was decreased after all treatments. Glutathione S-transferase (GST) activity was higher than the control levels in kidney of both fish exposed to pesticides. No significant changes were observed in malondialdehyde level in kidney and brain of C. carpio. Our results indicate that the toxicities of azinphosmethyl and 2,4-D may be related to oxidative stress. Also, the results show that SOD activity in gill and GST activity in kidney may be used as biomarkers for pollution monitoring and indicate that the activities of certain biomarkers in C. carpio are more sensitive to pesticides than those in O. niloticus.