Biomolecular Level Research Articles

Hybrid 2D nanomaterials as dual-mode contrast agents in cellular imaging.

The design of multifunctional nanofluids is highly desirable for biomedical therapy/cellular imaging applications.[1–4] The emergence of hybrid nanomaterials with specific properties, such as magnetism and fluorescence, can lead to an understanding of biological processes at the biomolecular level.[1] Various hybrid systems have been analyzed in the recent past for several possible biomedical applications.[5–9] Carbon-based hybrid systems such as carbon nanotubes with various nanoparticles are being widely tested for their biological applications because of their ability to cross cell membranes and their interesting thermal and electrical properties.[10,11] Graphene oxide (GO) is a fairly new graphene-based system with a 2D carbon honeycomb lattice decorated with numerous functional groups attached to the backbone: these functional groups make it an excellent platform for further attachment of nanoparticles and synthesis of hybrid materials. Cell viability studies on GO have been recently attempted, showing biocompatibility. [12,13] Moreover, the intrinsic photoluminescence (PL) properties of GO can be utilized for cellular imaging.[13] The large surface area and non-covalent interactions with aromatic molecules make GO an excellent system for biomolecular applications and drug attachment.

Multifunctional stable fluorescent magnetic nanoparticles

Because of their multifunctionality and unique magnetic properties, superparamagnetic iron oxide nanoparticles (SPIONs) have been recognized as very promising materials for various biomedical applications. The main difficulty with the use of SPIONs as multimodal bioimaging agents is their lack of fluorescence. Since cells can act as extremely efficient filters for the elution of surface-bound fluorescent tags with nanoparticles, the surface loaded fluorescence dyes significantly decay after a short period of time. Here, for the first time, we introduce novel, engineered multimodal SPIONs with a permanent fluorescence capability, the study of which can lead to a deeper understanding of biological processes at the biomolecular level, greatly influencing molecular diagnostics, imaging and therapeutic applications.

Studying the Bacterial Flagellar Motor using an Optical Torque Wrench

At the biomolecular level, the physical quantity torque manifests itself in a number of ways e.g. in the conformational changes of biopolymers such as DNA and in actions of both linear and rotary molecular motors. The optical torque wrench, an optical tweezers setup with the capability of applying and measuring both force and torque, has been developed as a versatile setup in tackling biologically relevant issues at high spatial and temporal resolution. Torque control in this optical tweezers setup relies on the manipulation and readout of the polarization state of light used to trap nano-fabricated birefringent cylinders.

Effects of Carbon Nanotube-Tethered Nanosphere Density on Amperometric Biosensing: Simulation and Experiment

Nascent nanofabrication approaches are being applied to reduce electrode feature dimensions from the microscale to the nanoscale, creating biosensors that are capable of working more efficiently at the biomolecular level. The development of nanoscale biosensors has been driven largely by experimental empiricism to date. Consequently, the precise positioning of nanoscale electrode elements is typically neglected, and its impact on biosensor performance is subsequently overlooked. Herein, we present a bottom-up nanoelectrode array fabrication approach that utilizes low-density and horizontally oriented single-walled carbon nanotubes (SWCNTs) as a template for the growth and precise positioning of Pt nanospheres. We further develop a computational model to optimize the nanosphere spatial arrangement and elucidate the trade-offs among kinetics, mass transport, and charge transport in an enzymatic biosensing scenario. Optimized model variables and experimental results confirm that tightly packed Pt nanosphere/...

Characterizing variability in in vivo Raman spectroscopic properties of different anatomical sites of normal tissue in the oral cavity

AbstractRaman spectroscopy is an inelastic light scattering technique that is capable of probing biochemical and biomolecular structures and conformations of tissue. This study aims to characterize the in vivo Raman spectroscopic properties of different normal oral tissues in the fingerprint region (800–1800 cm−1) and to assess distinctive biochemical variations of different anatomical regions in the oral cavity. A specially designed fiber‐optic Raman probe with a ball lens was utilized for real‐time, in vivo Raman measurements of various oral tissue sites (i.e. inner lip, attached gingiva, floor, dorsal tongue, ventral tongue, hard palate, soft palate, and buccal). The semiquantitative non‐negativity‐constrained least squares minimization fitting of reference biochemicals representing oral tissue constituents (i.e. hydroxyapatite, keratin, collagen, DNA, and oleic acid) and partial least squares‐discriminant analysis (PLS‐DA) were employed to assess the significance of inter‐anatomical variability. A total of 402 high‐quality in vivo oral Raman spectra were acquired from 20 subjects. The histological characteristics of different oral tissues were found to have influence on the in vivo Raman spectra and could be grossly divided into three major clusterings: (1) buccal, inner lip, and soft palate; (2) dorsal, ventral tongue, and floor; (3) gingiva and hard palate. The PLS‐DA multiclass algorithms were able to identify different tissue sites with varying accuracies (inner lip 83.1%, attached gingiva 91.3%, floor 86.1%, dorsal tongue 88.8%, ventral tongue 83.1%, hard palate 87.6%, soft palate 83.3%, and buccal mucosa 85.3%), bringing out the similarities among different oral tissues at the biomolecular level. This study discloses that inter‐anatomical variability is significant and should be considered as an important parameter in the interpretation and rendering of Raman diagnostic algorithms for oral tissue diagnosis and characterization. Copyright © 2011 John Wiley & Sons, Ltd.

Disinfection effect and its mechanism of electrolyzed oxidizing water on spores of Bacillus subtilis var. niger

A study was carried out on the disinfection efficiency of electrolyzed oxidizing water (EOW) on spores of Bacillus subtilis var. niger. The results showed a remarkable fungicidal rate of 100% after 20 min duration of 191 mg/L active available chlorine (ACC). The disinfection effect was improved with increased ACC or prolonged disinfection time, while organic interferents exerted a strong concentration-dependent inhibition against the disinfection. The disinfection mechanism was also investigated at bio-molecular level. EOW decreased dehydrogenase activity, intensified membrane permeability, elevated suspension conductivity, and caused leakage of intracellular K+, proteins, and DNA, indicating a damage of cell walls and membranes. Effects of EOW on microbiological ultra-structures were also verified by transmission electronic microscopy (TEM) images, showing that EOW destroyed protective barriers of the microbe and imposed some damages upon the nucleus area.

Bioengineering of the Enterobacter aerogenes strain for biohydrogen production

Enterobacter aerogenes is one of the most widely-studied model strains for fermentative hydrogen production. To improve the hydrogen yield of E. aerogenes, the bioengineering on a biomolecular level and metabolic network level is of importance. In this review, the fermentative technology of E. aerogenes for hydrogen production will be first briefly summarized. And then the bioengineering of E. aerogenes for the improvement of hydrogen yield will be thoroughly reviewed, including the anaerobic metabolic networks for hydrogen evolution in E. aerogenes, metabolic engineering for improving hydrogen production in E. aerogenes and mixed culture of E. aerogenes with other hydrogen-producing bacteria to enhance the overall yield in anaerobic cultivation. Finally, a perspective on E. aerogenes as a hydrogen producer including systems bioengineering approach for improving the hydrogen yield and application of the engineered E. aerogenes in mixed culture will be presented.

Mass spectrometric analysis of long-lived radionuclides in bio-assays

During the past few decades releases of man-made radionuclides into the biosphere have created environmental contamination that has provoked public concern. This has also raised the need to accurately and in a timely manner determine the quantities of radionuclides in environmental samples and in bio-assays in order to assess their potential impact on public health. The wide spectrum of emission sources has resulted in heterogeneous structures and different isotopic compositions of the contamination that, in turn, has produced new and very specific elemental and isotopic features. Nowadays, mass spectrometry is increasingly used for the determination of many long-lived radionuclides with low specific activities in environmental and biological samples. In summary, the merits of particular mass spectrometric methods include (i) low detection limits (ICP-MS, TIMS, etc.), (ii) high precision of the measured isotopic ratios (multi-collector ICP-MS and TIMS), (iii) high selectivity and abundance sensitivity (RIMS, AMS), and (iv) possibility for a spatially resolved isotope analysis (SIMS, LA-ICP-MS). Mass spectrometric analysis of long-lived radionuclides has been employed in radiobiology and biomedical studies, environmental monitoring and remediation, climate research, and forensics. The implementation of imaging inorganic mass spectrometry in proteomic research is highly promising for the study of radionuclide speciation mechanisms in organs and tissue on a bio-molecular level. This paper summarises specific features of major radioactive contaminations that have occurred during the last few decades and discusses the merits of modern mass spectrometric techniques, with examples of the determination of long-lived isotopes of actinides and fission products in biological samples.

High-Grade Acute Organ Toxicity as Positive Prognostic Factor in Adjuvant Radiation and Chemotherapy for Locally Advanced Head and Neck Cancer

To test for an association between high-grade acute organ toxicity during adjuvant radiation and chemotherapy and treatment outcome in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Institutional review board approval was obtained for this retrospective study. From September 1994 to October 2008, 294 HNSCC patients were treated with adjuvant radiation and chemotherapy at the authors' department. They received normofractionated (2 Gy per fraction) irradiation to include associated nodal drainage sites, for a cumulative dose of 60-64 Gy. From January 2002 to December 2009, 91 patients received additional concomitant cisplatin-based chemotherapy. Toxicity during treatment was monitored weekly according to the common toxicity criteria (CTC); any CTC toxicity grade 3 or higher, including mucositis, dysphagia, or skin reaction, was considered high-grade acute organ toxicity. The influence of possible prognostic factors on overall survival and locoregional control was studied by means of uni- and multivariate Cox regression. A statistically significant association was found between high-grade acute organ toxicity and both overall survival and locoregional control. Patients with CTC grade 3 or greater acute organ toxicity had a 5-year overall survival and locoregional control rate of 90% and 97%, respectively, as compared with 24% and 74%, respectively, in patients without such toxicity (P < .01). Multivariate analyses revealed that this association was independent from other factors that may influence treatment toxicity, especially concomitant chemotherapy and/or radiation therapy. The data suggest that normal tissue and tumor tissue may behave similarly with respect to treatment response, as high-grade acute organ toxicity during radiation and chemotherapy was associated with better outcomes in the patient population; therefore, the hypothesis should be further analyzed on the biomolecular and clinical level and with other tumor entities in prospective clinical trials.

Engineered nanoparticles for biomolecular imaging

In recent years, the production of nanoparticles (NPs) and exploration of their unusual properties have attracted the attention of physicists, chemists, biologists and engineers. Interest in NPs arises from the fact that the mechanical, chemical, electrical, optical, magnetic, electro-optical and magneto-optical properties of these particles are different from their bulk properties and depend on the particle size. There are numerous areas where nanoparticulate systems are of scientific and technological interest, particularly in biomedicine where the emergence of NPs with specific properties (e.g. magnetic and fluorescence) for contrast agents can lead to advancing the understanding of biological processes at the biomolecular level. This review will cover a full description of the physics of various imaging methods, including MRI, optical techniques, X-rays and CT. In addition, the effect of NPs on the improvement of the mentioned non-invasive imaging methods will be discussed together with their advantages and disadvantages. A detailed discussion will also be provided on the recent advances in imaging agents, such as fluorescent dye-doped silica NPs, quantum dots, gold- and engineered polymeric-NPs, superparamagnetic iron oxide NPs (SPIONs), and multimodal NPs (i.e. nanomaterials that are active in both MRI and optical methods), which are employed to overcome many of the limitations of conventional contrast agents (e.g. gadolinium).

Tolerance to oxidative stress induced by desiccation in Porphyra columbina (Bangiales, Rhodophyta)

Unravelling the mechanisms underlying desiccation tolerance is crucial in order to understand the position of algal species in the intertidal zone. The alga Porphyra columbina lives in the uppermost part of the rocky intertidal zones around the world and was selected as a model for this study. Naturally desiccated plants were collected during low tide and studied for morphological changes, oxidative burst induction, biomolecule oxidation, antioxidant responses, and photosynthetic status. Naturally hydrated plants collected during high tides were used for comparative purposes. In addition, changes induced by desiccation were assessed in vitro and the capacity to recover from desiccation was determined by rehydrating the fronds in seawater. The global results show that desiccation induces morphological and cellular alterations accompanied by a loss of ∼96% of the water content. Overproduction of reactive oxygen species (ROS) was induced by desiccation and two peaks of H2O2 were detected at 1 and 3 h of desiccation. However, during in vitro rehydration post-desiccation, the ROS quickly returned to the basal levels. At the biomolecular level, only a low production of oxidized proteins was recorded during desiccation, whereas the activity of diverse antioxidant enzymes increased. However, this activity diminished to near basal levels during rehydration. The photosynthetic efficiency (Fv/Fm) during desiccation declined by 94–96% of the values recorded in hydrated plants. This reduction was generated by the low levels of trapped energy flux per cross-section (TRo/CS), electron transport flux per CS (ETo/CS), and density of reaction centres (RC/SCo) as well as the chlorophyll content. The inverse pattern was observed for the levels of phycocyanin and phycoerythrin content. Fv/Fm and the photosynthetic indicators were restored to normal levels after only 5 min of rehydration. The results indicate that desiccation in P. columbina causes overproduction of ROS that is efficiently attenuated. The morphological and photosynthetic changes could be operating as tolerance mechanisms due to the fact that these responses principally prevent biomolecular alteration and cellular collapse. Thus, the activation of different physiological mechanisms helps to explain the high tolerance to desiccation of P. columbina and, at least in part, the position of this species at the highest level in the intertidal zone.

Diabetes Mellitus: Clinical and Biochemical Perspectives

Diabetes mellitus is a disease in which the body cannot produce or properly use insulin, a hormone necessary for the uptake of glucose in cells. According to the American Diabetes Association, 23.6 million people in the United States (7.8% of the population) have diabetes. There are three distinct types of diabetes – type I, type II, and gestational – but this project will look specifically at types I and II which are characterized by failure to produce insulin and by insulin resistance respectively. Both type I and type II diabetes leave glucose free to circulate in the bloodstream since cells cannot take up this glucose without insulin present. High concentrations of glucose in the bloodstream have been shown to cause acute and long‐term health complications such as diabetic ketoacidosis, glycosuria, polyuria, nerve and tissue damage, retinopathy, stroke, and kidney disease, all of which we will present from a clinical perspective. We will also examine diabetes mellitus from the biomolecular level by investigating the relationship between hyperglycemia, PKCε activation, and β cell dysfunction. Additionally, we will research one particular diabetic complication – retinopathy – at the biomolecular level. Results will be discussed in terms of abnormal renal vasodilatation and vascular permeability through PKC‐dependent mechanisms.

Mechanical behavior of human mesenchymal stem cells during adipogenic and osteogenic differentiation

Human mesenchymal stem cells (hMSCs) have gained widespread attention in the field of tissue engineering but not much is known about the changes of mechanical properties during the process of cell lineage commitment and the mechanisms of these behaviors. It is believed that exploring the inter-relations between stem cells mechanical properties and lineage commitment will shed light on the mechanobiology aspect of differentiation. hMSCs were cultured in adipogenic and osteogenic mediums and the elastic moduli were monitored using micropipette aspiration. It was found that hMSCs undergoing osteogenesis have an instantaneous Young’s modulus of 890±219Pa and an equilibrium Young’s modulus of 224±40Pa, each is about 2-fold higher than the control group. Interestingly, cells cultured in adipogenic medium exhibited a slight increase in the cellular modulus followed by a decrease relative to that of the control group. Gene expression study was employed to gain insights into this phenomenon. Concomitant up regulation of actin binding filamin A (FLNa) and γ-Tubulin with the cellular elastic modulus indicated their important role in mechanical regulation during hMSCs differentiation. Statistical results showed that cell shape and cell area changed with cellular mechanical properties, which means that cell morphology has a close relation with cell elastic modulus in the initial stage of differentiation. Collectively, these results provide a quantitative description of hMSCs mechanical behavior during the process of differentiation as well as the possible accompanying mechanism at the biomolecular level.

Tattoo: a navigational tool, a lighthouse for biomolecular level precision in surgical endoscopy. Newton’s apple or Eve’s?

Unchanged for more than half a century, the World Health Organization (WHO) defines health as a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity. Laparoscopic surgery has successfully managed the physical aspect of disease, enhanced mental well-being by its aesthetic virtues and by being less painful, and enhanced the social value by enabling early resumption of normal activity profile. The ongoing evolution of this revolutionary technique keeps bettering outcomes on all parameters. Surgical outcomes are the primary determinant of patient satisfaction [1]. Surgery leaves a scar not only on the body but on the mind as well [2]. Avoiding disruption of a tattoo is a welcome development that is sure to enhance the mental and psychosocial well-being of our patients [3]. The laparoscopic surgeon has continued to challenge his best outputs in a precise pursuit for perfection to better the best. Laparoscopic surgeons, who were ostracized in the early 1990s and called names such as ‘‘boys with toys’’ nearly killing their patients and disparagers married to ‘‘Nintendo surgery,’’ have come a long way to become the envy of once hostile brotherhood [4]. Consorting technology, laparoscopic surgeons have never failed to question and reshape themselves holistically with ever-evolving paradigms. Rising like a Phoenix from a breed of dying species, the laparoscopic surgeon has evolved with a larger canvas, the description of which goes by various names, i.e., cyber surgeon, endosurgeon, space surgeon, molecular surgeon, or biosurgeon [5]. This progress has been nurtured and sustained by societies, such as The Society of American Gastrointestinal and Endoscopic Surgeons and The European Association for Endoscopic Surgery, and above all by the Journal of Surgical Endoscopy. Surgery is a craft no different than art, because both of them are the result of some imitation and some variation [6]. Most renaissance intellectuals, including Leonardo da Vinci, had a common source of inspiration, as is the case with the biomedical scientists and the endosurgeon, the ambassador of the marriage of a craft with the art [6]. Surgical endoscopy is the common thread for all the good work that has contributed to the present status leading to improved patientperceived outcomes on physical, social, and mental parameters. Avoidance of tattoo disruption is one such benefit of laparoscopic surgery [3]. It not only preserves the tattoo but also the basic tenets of informed consent. It preempts the fiducial, coercive moments in the communication for an informed consent. Tattoos have adorned humankind for more than 5,000 years. Despite ridicule from orthodoxy (‘‘Ye shall not make any cuttings in your flesh for the dead, nor print any marks upon you’’ Leviticus 19:28), tattoos have gained social acceptance as status symbols, declaration of love/ sensuality/sexuality, or signs of religious beliefs. Tattoos, seen as a trivial appendage by some have become a fashion statement of visual expression of individuality to be seen as an extension of the wearer’s personality. Tattoos occupy the grey zone between virtue and vice on the perceptive social horizon. They evoke a potpourri of imagery in different souls, from sensual to intellectual to medicinal. It is something like the image of an apple that reminds us of either Eve or Newton or an iPod or simply the goodness of the fruit. It is in this light that the article by Gilliam et al. B. B. Agarwal (&) Dr. Agarwal’s Surgery & Yoga, F81 & 82, Street No. 4, Virender Nagar, New Delhi 10058, India e-mail: endosurgeon@gmail.com

Therapeutic potential of low-intensity ultrasound (part 1): thermal and sonomechanical effects.

In this first part of the review, we will focus on and discuss various aspects of low-intensity ultrasound (US), with emphasis on mild thermal effects, apoptosis induction, and sonomechanical effects. Mild thermal effects of US have been commonly applied to physical therapy. Though US has clear beneficial effects, the advantage of using US over other heating modalities remains unclear. US has also been used in vivo and clinically in the treatment of wounds and fractures, with promising results. On the biomolecular level, studies have shown that US can induce apoptosis and that certain conditions can provide optimal apoptosis induction. As to potential therapeutic applications, in addition to the thermal and other physical effects, apoptosis induction by US may offer direct and rapid treatment of tumors or cancer tissues. Technological advances and rapidly accelerating research in this field are providing an ever-increasing array of therapeutic options for lowintensity US.

Fuzzy ensemble clustering based on random projections for DNA microarray data analysis

Two major problems related the unsupervised analysis of gene expression data are represented by the accuracy and reliability of the discovered clusters, and by the biological fact that the boundaries between classes of patients or classes of functionally related genes are sometimes not clearly defined. The main goal of this work consists in the exploration of new strategies and in the development of new clustering methods to improve the accuracy and robustness of clustering results, taking into account the uncertainty underlying the assignment of examples to clusters in the context of gene expression data analysis. We propose a fuzzy ensemble clustering approach both to improve the accuracy of clustering results and to take into account the inherent fuzziness of biological and bio-medical gene expression data. We applied random projections that obey the Johnson-Lindenstrauss lemma to obtain several instances of lower dimensional gene expression data from the original high-dimensional ones, approximately preserving the information and the metric structure of the original data. Then we adopt a double fuzzy approach to obtain a consensus ensemble clustering, by first applying a fuzzy k-means algorithm to the different instances of the projected low-dimensional data and then by using a fuzzy t-norm to combine the multiple clusterings. Several variants of the fuzzy ensemble clustering algorithms are proposed, according to different techniques to combine the base clusterings and to obtain the final consensus clustering. We applied our proposed fuzzy ensemble methods to the gene expression analysis of leukemia, lymphoma, adenocarcinoma and melanoma patients, and we compared the results with other state of the art ensemble methods. Results show that in some cases, taking into account the natural fuzziness of the data, we can improve the discovery of classes of patients defined at bio-molecular level. The reduction of the dimension of the data, achieved through random projections techniques, is well-suited to the characteristics of high-dimensional gene expression data, thus resulting in improved performance with respect to single fuzzy k-means and with respect to ensemble methods based on resampling techniques. Moreover, we show that the analysis of the accuracy and diversity of the base fuzzy clusterings can be useful to explain the advantages and the limitations of the proposed fuzzy ensemble approach.

Clinical relevance of predictive physiologically based pharmacokinetic methods

Background: The prediction of human pharmacokinetics from data generated in relevant in vitro screens, and/or from pharmacokinetics determined in preclinical species, is of rapidly increasing interest throughout drug discovery, development and beyond. Objective: To provide a brief overview of the methods available for pharmacokinetic prediction and describe some of the advantages to be obtained from its application. Methods: Because of the relative degree of realism in the models, and the corresponding richness of the data available for model development, the technique of physiologically based pharmacokinetic (PBPK) modelling offers the best means of performing clinically relevant pharmacokinetic prediction. A small number of selected examples from the literature that illustrate significant applications of PBPK modelling are described. Results/conclusion: The development of reliable clinical pharmacokinetic prediction is critically dependent on, and will follow on from, further improvements in the quantitative determination of relevant processes at the biomolecular level. When combined with efficacy and toxicity data to predict in vivo pharmacological and toxic responses, the PBPK model will prove to be an indispensable tool in drug discovery and development.

Gene expression modeling through positive boolean functions

In the framework of gene expression data analysis, the selection of biologically relevant sets of genes and the discovery of new subclasses of diseases at bio-molecular level represent two significant problems. Unfortunately, in both cases the correct solution is usually unknown and the evaluation of the performance of gene selection and clustering methods is difficult and in many cases unfeasible. A natural approach to this complex issue consists in developing an artificial model for the generation of biologically plausible gene expression data, thus allowing to know in advance the set of relevant genes and the functional classes involved in the problem. In this work we propose a mathematical model, based on positive Boolean functions, for the generation of synthetic gene expression data. Despite its simplicity, this model is sufficiently rich to take account of the specific peculiarities of gene expression, including the biological variability, viewed as a sort of random source. As an applicative example, we also provide some data simulations and numerical experiments for the analysis of the performances of gene selection methods.

Chronic Myeloid Leukemia in Two Patients with Gastrointestinal Stromal Tumor.

Imatinib competitively binds to the ATP binding site of Bcr-Abl kinase and inhibits Abl tyrosine kinase activity. Most patients with chronic myeloid leukemia (CML) achieve clinically relevant hematologic and cytogenetic responses to imatinib. It is also a potent inhibitor of a receptor-type c-Kit tyrosine kinase. Therefore, it was examined for therapeutic efficacy against malignant Gastrointestinal Stromal Tumor (GIST), which is a rare tumor of the gastrointestinal tract and is mainly caused by aberrant expression of a mutated c-Kit that is constitutively active without binding of a ligand, stem cell factor. We report two rare cases of double cancer involving CML and GIST. The first case is a 66-year-old Japanese male patient who was presented to our hospital with leukothrombocytosis on February 27, 2006. The patient was diagnosed to be suffering from CML by the presence of Philadelphia chromosome. Several days later, he was admitted with acute peritonitis. A ruptured tumor on 80 cm oral side of ileum end was found by an emergency partial ilectomy. Microscopically, spindle-shaped and round epithelioid cells were growing externally from the intestinal muscular propia. Immunohistochemical analysis showed that the tumor cells were positive for c-kit and CD34 and negative for S-100 protein and desmin. The tumors were identified as GIST. Imatinib was administered to treat CML on the 8th postoperative day. The second case is a 57-year-old Japanese female patient who was presented to our hospital with marked thrombocytosis on March 6, 2006. The patient was diagnosed to be suffering from CML by the presence of Philadelphia chromosome. One year ago, she underwent distal gastrectomy for submucosal tumor. Pathological examination revealed proliferation of submucosal spindle-shaped cells with elongated cigar-shaped nuclei arranged in fascicles. Immunohistochemical stains confirmed the diagnosis of GIST.These two cases provided a valuable opportunity for treating GIST with CML. We look forward to active effect of imatinib, not only in CML treatment but also in preventing recurrence of GIST. The occurrence mechanism of either CML or GIST at the biomolecular level has been established. However, we can show no relation between these malignancies. Therefore, it is natural for us to understand accidental coincidence. We should follow-up these patients carefully. Accumulation of such cases may contribute to clarify more precise mechanism of tumorgenesis.

Transcription of ethylene perception and biosynthesis genes is altered by putrescine, spermidine and aminoethoxyvinylglycine (AVG) during ripening in peach fruit (Prunus persica)

The time course of ethylene biosynthesis and perception was investigated in ripening peach fruit (Prunus persica) following treatments with the polyamines putrescine (Pu) and spermidine (Sd), and with aminoethoxyvinylglycine (AVG). Fruit treatments were performed in planta. Ethylene production was measured by gas chromatography, and polyamine content by high-performance liquid chromatography; expression analyses were performed by Northern blot or real-time polymerase chain reaction. Differential increases in the endogenous polyamine pool in the epicarp and mesocarp were induced by treatments; in both cases, ethylene production, fruit softening and abscission were greatly inhibited. The rise in 1-aminocyclopropane-1-carboxylate oxidase (PpACO1) mRNA was counteracted and delayed in polyamine-treated fruit, whereas transcript abundance of ethylene receptors PpETR1 (ethylene receptor 1) and PpERS1 (ethylene sensor 1) was enhanced at harvest. Transcript abundance of arginine decarboxylase (ADC) and S-adenosylmethionine decarboxylase (SAMDC) was transiently reduced in both the epicarp and mesocarp. AVG, here taken as a positive control, exerted highly comparable effects to those of Pu and Sd. Thus, in peach fruit, increasing the endogenous polyamine pool in the epicarp or in the mesocarp strongly interfered, both at a biochemical and at a biomolecular level, with the temporal evolution of the ripening syndrome.