The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a genetherapytarget. Significant advancements have been made in understanding...Full Text Available
The 37/67-kd laminin receptor, LAMR, is a multifunctional protein that associates with the 40S ribosomal subunit and also localizes to the cell membrane to interact with the extracellular matrix. LAMR...Full Text Available
The technology of genetargeting through homologous recombination has been extremely useful for elucidating gene functions in mice. The application of this technology was thought impossible in the large...Full Text Available
The ability to achieve tumor selective expression of therapeutic genes is an area that needs improvement for cancer genetherapy to be successful. One approach to address this is through the...Full Text Available
A technique for delivering genes carried by recombinant retroviruses into specific cell types could have numerous applications in oncology, developmental biology, and genetherapy. As a first step toward this remote goal the authors designed a procedure allowing in vitro cell targeting by retroviruses. Biotinylated antibodies against the viral envelope protein on one side, and against specific cell membrane markers on the other side, were bridged by streptavidin and used to link the virus to the host. The method was successfully used to infect human cells with ecotropic murine retroviruses by means of major histocompatibility complex class I and class II antigens and appears easily adaptable to other cell, membrane markers. Moreover, the sequential protocol they design, although allowing infection of human cells, requires less stringent safety constraints than would handling of amphotropic virus stocks.
Ewing's sarcoma is a small round-cell tumor typically arising in the bones, rarely in soft tissues, of children and adolescents. Ewing's sarcoma has retained the most unfavorable prognosis of all primary musculoskeletal tumors. Prior to the use of multi-drug chemotherapy, long-term survival was less than 10%. The development of multi-disciplinary therapy with chemotherapy, irradiation, and surgery has increased current long-term survival rates in most clinical centers to greater than 50%. In addition, the preferred method of tumor resection has changed; limb salvage has nearly replaced amputation of the affected limb. Limb salvage procedures can be performed in place of amputation without compromising patient survival rates. Recent studies have revealed that the pathognomonic translocations involving the EWS gene on chromosome 22 and an ETS-type gene, which is most commonly the Fli1 gene on chromosome ...
All microRNA (miRNA) target—finder algorithms return lists of candidate targetgenes. How valid is that output in a biological setting? Transcriptome analysis has proven to be a useful approach...Full Text Available
In animal models, single-gene mutations in genes involved in insulin/IGF and target of rapamycin signalling pathways extend lifespan to a considerable extent. The genetic, genomic and epigenetic influences...Full Text Available
The findings reported in this study highlight several important features of the development of hematopoietic stem cells after transplantation into irradiated recipients. First, they demonstrate the existence of a class of primitive multipotential stem cells that can function for a significant portion of the lifetime of a mouse (15 mo). In addition, they clearly show that these primitive stem cells can be infected with recombinant retroviruses and thus would be appropriate targets for genetherapy in somatic tissues. Second, our data indicate that the progeny of some, but not all, of the primitive stem cells have fully expanded into the various hematopoietic lineages by 2 mo after reconstitution. Finally, our analysis of the secondary recipients provides strong evidence suggesting that the primitive stem cell population can actually clonally expand. Our current experiments are aimed at determining the extent to which this ...
Human antibodies targeting prostate cancer cell surface epitopes may be useful for imaging and therapy. The objective of this study was to evaluate the tumor targeting of an internalizing human...Full Text Available
Histone Arg methylation and Lys acetylation have been found to cooperatively regulate the expression of p53 targetgenes. Peptidylarginine deiminase 4 (PAD4) is an enzyme that citrullinates...Full Text Available
An electron accelerator unit is described for electron beam therapy, comprising: a source of an electron beam; means for finally directing at least a portion of the beam to a therapy site, the directing means being mechanically independent of, and electrically isolated from, the source, and having a target area; and means for aligning the source with the directing means, the aligning means comprising means for projecting at least one beam of light from the source toward the target area.
An electron accelerator unit is described for electron beam therapy, comprising: a source of an electron beam; means for finally directing at least a portion of the beam to a therapy site, the directing means being mechanically independent of, and electrically isolated from, the source, and having a target area; and means for aligning the source with the directing means, the aligning means comprising means for projecting at least one beam of light from the source toward the target area.
URA5 genes encode orotidine-5′-monophosphate pyrophosphorylase (OMPpase), an enzyme involved in pyrimidine biosynthesis. We cloned the Histoplasma capsulatum URA5...Full Text Available
Optimal sample handling techniques for tissue preparation and storage, RNA extraction and quantification, and targetgene detection are crucial for reliable gene expression analysis. Methods...Full Text Available
Gene silencing is a useful technique for elucidating biological function of genes by knocking down their expression. A recently developed artificial microRNAs (amiRNAs) exploits an endogenous...Full Text Available
Background: EGFR (epidermal growth factor receptor) and VEGF (vascular endothelial growth factor) inhibitors confer clinical benefit in metastatic colorectal cancer when combined with chemotherapy. An emerging strategy to improve outcomes in rectal cancer is to integrate biologically active, targeted agents as triple therapy into chemoradiation protocols. Material and methods: cetuximab and bevacizumab have now been incorporated into phase I-II studies of preoperative chemoradiation therapy (CRT) for rectal cancer. The rationale of these combinations, early efficacy and toxicity data, and possible molecular predictors for tumor response are reviewed. Computerized bibliographic searches of Pubmed were supplemented with hand searches of reference lists and abstracts of ASCO and ASTRO meetings. Results: the combination of cetuximab and CRT can be safely applied without dose compromises of the respective treatment components. ...
BackgroundPolyethyleneimine (PEI), which can interact with negatively charged DNA through electrostatic interaction to form nanocomplexes, has been widely attempted to use as a gene...Full Text Available
Epidermal growth factor receptor (EGFR) related therapies – mainly tyrosine kinase inhibitors (TKIs) such as erlotinib and gefitinib, but also monoclonal antibodies targeting EGFR, for example,...Full Text Available
The heterogeneity of metastatic breast cancer mandates the need to select therapies taking into account tumor and patient characteristics. Chemotherapy is indicated in the palliative setting especially...Full Text Available
The success of monoclonal antibodies in clinical practice is dependent on good design. Finding a suitable target is the most important part as other properties of the antibody can be altered by genetic...Full Text Available
The potential of radiolabelled phenylpiperazines as agents for the detection and therapy of tumours of neural crest origin was evaluated by in vitro pharmacological studies with human neuroblastoma...Full Text Available
PurposeWe conducted a comparative study of Clinical Target Volume (CTV) definition of pelvic lymph nodes by multiple GU radiation oncologists looking at the levels...Full Text Available
PURPOSE: Hepatocellular carcinoma (HCC) is a highly virulent malignancy with no effective treatment thus requiring innovative and effective targetedtherapies. The oncogene Astrocyte elevated gene-1 (AEG-1) plays a seminal role in hepatocarcinogenesis and profoundly downregulates insulin-like growth factor binding protein-7 (IGFBP7). The present study focuses on analyzing potential tumor suppressor functions of IGFBP7 in HCC and the relevance of IGFBP7 downregulation in mediating AEG-1 function.EXPERIMENTAL DESIGN: IGFBP7 expression was detected by immunohistochemistry in HCC tissue microarray and real-time PCR and ELISA in human HCC cell lines. Dual Fluorescence in situ hybridization was performed to detect loss of heterozygosity at IGFBP7 locus. Stable IGFBP7-overexpressing clones were established in the background of AEG-1-overexpressing human HCC cells and were analyzed for in vitro proliferation and senescence and in ...
Electron beam therapy has often been used for radiation therapy of carcinomas of the buccal mucosa, though side effects, including stomatitis and dermatitis, are known to exist. We experimented using the additional back scatter and transit with the phantom under a lead plate within the irradiation field, in order to better focus the dose on the target volume moreover, we fabricated a mouthpiece fitted with a lead plate shaped to the target volume, and with respect to the influence of the mouthpiece on stomatitis and dermatitis, obtained good clinical results. (author).
Electron beam therapy has often been used for radiation therapy of carcinomas of the buccal mucosa, though side effects, including stomatitis and dermatitis, are known to exist. We experimented using the additional back scatter and transit with the phantom under a lead plate within the irradiation field, in order to better focus the dose on the target volume moreover, we fabricated a mouthpiece fitted with a lead plate shaped to the target volume, and with respect to the influence of the mouthpiece on stomatitis and dermatitis, obtained good clinical results. (author).
Conformal radiation therapy represents a considerable and attractive challenge in oncology. Its aim is mainly to improve local control by increasing the dose with an acceptable rate of complications. This work overviews the world literature on this subject. The technical and theoretical requirements are highlighted. These requirements include a precise definition of the target volume by digital imaging (essentially CT scan), but also clear view of the target volume and the organs at risk, a specific collimation of the beam, 3-D dose calculations, optimization procedures, and a rigid immobilization of the patient with verification of his position. Moreover, the clinical applications of conformal radiation therapy are reviewed and discussed. (authors). 80 refs., 1 tab.
We investigate a method for gene delivery to vascular smooth muscle cells using ultrasound triggered delivery of plasmid DNA from electrostatically coupled cationic microbubbles. Microbubbles...Full Text Available
MicroRNAs (miRNAs) are short non-coding RNAs that play a central role in regulation of gene expression by binding to targetgenes. Many miRNAs were associated with the function of the central nervous...Full Text Available
BackgroundGene expression profiling and the analysis of protein-protein interaction (PPI) networks may support the identification of disease bio-markers and potential drug targets....Full Text Available
We have characterized the kinetic response of genetargets throughout the murine genome to transcriptional modulation by the glucocorticoid receptor (GR). In contrast to a model in which multiple genes...Full Text Available
Short-hairpin RNA (shRNA)–mediated gene knockdown is a powerful tool for targetedgene silencing and an emerging novel therapeutic strategy. Recent publications, however, reported unexpected...Full Text Available
Despite high local control rate in Ewing's sarcoma the exact indication of radiation therapy is still controversial as well as the choice of the target volume and the optimal dose of radiation. The importance of the quality of radiotherapy has been stressed in recently published data and has shown a significant impact on long term local control with adequate radiation therapy. The dramatic improvement of precision allowed by the conformal therapy and three dimensional dosimetry allow to expect a decrease of late effects expected for second malignancies. However, late sequelae and radio-induced osteosarcoma still remain the major side effects after radiotherapy. The authors discuss the results of the main trials on Ewing's sarcoma on the choice of dose and target volume. Surgery is still the preferred choice for small tumors if the foreseen outcome is identical. (authors). 28 refs.
A nonviral vector for highly efficient site-specific integration would be desirable for many applications in transgenesis, including genetherapy. In this study we directly compared the genomic integration...Full Text Available
Atypical hemolytic uremic syndrome (aHUS) is a heterogeneous disease that is caused by defective complement regulation in over 50% of cases. Mutations have been identified in genes encoding both complement...Full Text Available
Recent reports confirm that, due to the presence of long-lived, latently infected cell populations, eradication of human immunodeficiency virus type 1 (HIV-1) from infected patients by using antiretroviral...Full Text Available
The etiology of major depression remains unknown, but dysfunction of serotonergic signaling has long been implicated in the pathophysiology of this disorder. p11 is an S100 family member recently...Full Text Available
Human blinding disorders are often initiated by hereditary mutations that insult rod and/or cone photoreceptors and cause subsequent cellular death. Generally, the disease phenotype can be predicted...Full Text Available
BackgroundRecessive mutations in guanylate cyclase-1 (Gucy2d) are associated with severe, early onset Leber congenital amaurosis-1(LCA1). Gucy2d...Full Text Available
SummaryEpigenetic drugs have been shown to enhance gene expression and drug sensitivity in ovarian cancer cell lines and animal models. Based on promising pre-clinical studies,...Full Text Available
Recombinant adenoviruses have been widely used for various applications, including protein expression and genetherapy. We herein report a new and simple cloning approach to an efficient and robust...Full Text Available
Targeted genome capture combined with next-generation sequencing was used to analyze 2.9 Mb of the DFNB79 interval on chromosome 9q34.3, which includes 108 candidate genes. Genomic...Full Text Available
AbstractThe optimal definition of the size, shape and location of gross tumour volume is one of the most important steps in the planning of radiation therapy, and necessitates a proper...Full Text Available
Monogenic autoinflammatory diseases encompass a distinct and growing clinical entity of multisystem inflammatory diseases with known genetic defects in the innate immune system. The diseases...Full Text Available
BackgroundStem cell characteristics are an important feature of human cancer cells and play a major role in the therapy resistance of tumours. Strategies to target cancer stem cells...Full Text Available
BackgroundIntrafractional motion results in local over- and under-dosage in particle therapy with a scanned beam. Scanned beam delivery offers the possibility to compensate target...Full Text Available
Neuropilin-1 (NRP1) acts as a co-receptor for class 3 semaphorins and vascular endothelial growth factor and is an attractive angiogenesis target for cancer therapy. In addition to the transmembrane...Full Text Available
Using an adenoviral system as a delivery mediator of therapeutic gene, we investigated the therapeutic effects of the use of combined MDR1 shRNA and human NIS (hNIS)...Full Text Available
Purpose: The purpose of this study was to evaluate the efficacy and toxicity of replication-competent adenovirus-mediated double suicide genetherapy in an adjuvant setting with external beam radiation therapy (EBRT) in an experimental prostate cancer model in preparation for a Phase I clinical study in humans. Methods: For efficacy studies, i.m. DU145 and intraprostatic LNCaP C4-2 tumors were established in immune-deficient mice. Tumors were injected with the lytic, replication-competent Ad5-CD/TKrep adenovirus containing a cytosine deaminase (CD)/herpes simplex virus thymidine kinase (HSV-1 TK) fusion gene. Two days later, mice were administered 1 week of 5-fluorocytosine + ganciclovir (GCV) prodrug therapy and fractionated doses of EBRT (trimodal therapy). Tumor control rate of trimodal therapy was compared to that of EBRT alone. For ...
The main goal of local drug delivery is to increase the concentration of a specific therapeutic agent in a target tissue with minimal nontarget distribution. Compared to systemic therapy, local drug delivery provides a high level of therapeutic efficacy with minimal systemic effects. The current primary imaging modality for drug delivery has been x-ray angiography, but it has major limitations including anatomical ambiguity and inability to visualize the targeted tissues. Due to these inherent problems, MR guidance has been explored as an alternative imaging modality for guiding and monitoring of drug therapy. Recently, interventional MR (XMR) systems have been implemented that have both dual x-ray and MRI capabilities in a single suite and allow for real-time interventional procedures to ...
p53 plays a critical role in tumor suppression. As a transcription factor, in response to stress signals, p53 regulates its targetgenes and initiates stress responses, including cell cycle arrest,...Full Text Available
The development of new methods for gene addition to mammalian genomes is necessary to overcome the limitations of conventional genetic engineering strategies. Although a variety of DNA-modifying enzymes...Full Text Available
Inducible gene expression appears to be an essential event that couples light to entrainment of the master mammalian circadian clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus....Full Text Available
As the result of genetic alterations and tumor hypoxia, many cancer cells avidly take up glucose and generate lactate through lactate dehydrogenase A (LDHA), which is encoded by a targetgene of c-Myc...Full Text Available
BackgroundASCL1 role in pancreatic endocrine tumourigenesis has not been established. Recently it was suggested that ASCL1 negatively controls expression of the...Full Text Available
Several Bartonella species have now been implicated as human pathogens. The recovery of these fastidious organisms in the clinical microbiology laboratory remains difficult, and current...Full Text Available
This study used a PCR-based approach targeting 16S rRNA gene fragments to determine the occurrence and association of the three bovine digital dermatitis (BDD) treponeme phylogroups within lesions found...Full Text Available
BackgroundFormation of site specific genomic double strand breaks (DSBs), induced by the expression of a pair of engineered zinc-finger nucleases (ZFNs), dramatically increases the...Full Text Available
BackgroundMale infertility is a common cause of reproductive failure in humans. In mice, targeted deletions of the genes coding for FKBP6 or FKBP52, members of the FK506 binding...Full Text Available
A conserved multi-subunit complex (MybMuvB, MMB), regulates transcriptional activity of many different targetgenes in Drosophila somatic cells. A paralogous complex, tMAC, controls...Full Text Available
Glioblastoma multiforme is the most aggressive form of human brain tumor, which has no effective cure. Previously, we have demonstrated that overexpression of the C-terminal fragment of the human telomerase reverse transcriptase (hTERTC27) inhibits the growth and tumorigenicity of human cervical cancer HeLa cells. In this study, the therapeutic effect and molecular mechanisms of hTERTC27-mediated cancer genetherapy were further explored in vivo in established human glioblastoma xenografts in nude mice. We showed that intratumoral injection of adeno-associated virus carrying hTERTC27 (rAAV-hTERTC27) is highly effective in reducing the growth of the subcutaneously transplanted glioblastoma tumors. Histological analyses showed that rAAV-hTERTC27 treatment leads to profound necrosis, apoptosi...
Background: the authors report on the conception and first clinical application of a donut-shaped high-dose configuration for proton therapy (PT). This approach allows one to intensify target volume dose coverage for targets encompassing a critical, dose-limiting structure - like here, the cauda equina -, whilst delivering minimal dose to other healthy structures surrounding the target, thereby reducing the integral dose. Methods and results: intensity-modulated PT methods (IMPT) for spot scanning were applied to create and deliver a donut-shaped high-dose configuration with protons, allowing treating > 75% of the target with at least 95% of the prescribed dose of 72.8 CGE, whilst restricting dose to the cauda equina to 60-65 CGE. Integral dose was lower by a factor of 3.3 as compared to intensity-modulated radiotherapy with photons (IMXT). Conclusion: IMPT and spot scanning ...
Background: the authors report on the conception and first clinical application of a donut-shaped high-dose configuration for proton therapy (PT). This approach allows one to intensify target volume dose coverage for targets encompassing a critical, dose-limiting structure - like here, the cauda equina -, whilst delivering minimal dose to other healthy structures surrounding the target, thereby reducing the integral dose. Methods and results: intensity-modulated PT methods (IMPT) for spot scanning were applied to create and deliver a donut-shaped high-dose configuration with protons, allowing treating > 75% of the target with at least 95% of the prescribed dose of 72.8 CGE, whilst restricting dose to the cauda equina to 60-65 CGE. Integral dose was lower by a factor of 3.3 as compared to intensity-modulated radiotherapy with photons (IMXT). Conclusion: IMPT and spot scanning ...
RNA interference (RNAi) is an effective tool for studying gene function in oocytes, but no studies have targeted somatic cells of primary cultured cumulus cell-oocyte complexes (COCs). This...Full Text Available
MicroRNAs are short (∼22 nucleotides) noncoding RNAs that regulate the stability and translation of mRNA targets. A number of computational algorithms have been developed to help predict which...Full Text Available
The heat-shock gene, Hsp90, was targeted as a new variable genomic region to supplement other DNA-based tests for identification and discrimination of Globodera pallida, G. rostochiensis and G. tabacum tabacum. Populations of the potato cyst nematodes, G. pallida and G. rostochiensis (PCN), originating from Canada, France, Belgium and USA, together with two populations of G. tabacum tabacum from the USA and France were used for the amplification of a fragment of the Hsp90 gene. General and specific primers and probes for each species were derived from the consensus and non-consensus regions of the aligned sequences, respectively. A triplex conventional PCR assay, using a general forward and reverse or three specific reverse primers, as well as a real-time PCR using general primers and spec...
The long and resource intensive process of drug discovery and development is confronted with the basic challenge of providing effective and safe therapies at reasonably low costs. The better the mechanism of a disease is known, the higher the probability to find an appropriate therapy. Also, the better and earlier a disease can be diagnosed and characterized, the higher the chance to be able to interfere in this process with a chemical entity. This reasoning sets the framework for the use of imaging in drug discovery. We discuss the relevance of magnetic resonance imaging and spectroscopy to derive anatomical, functional, metabolic and target-related information in the context of pharmacological research in vivo. (author)
Many existing agents for diabetes therapy are unable to restore or maintain normal glucose homeostasis or prevent the eventual emergence of hyperglycemia-related complication. Therefore, agents based on novel mechanisms are sought to complement and extend the current therapeutic approaches. Based on the initial paper research, we focused on active STAT3 as an attractive pharmacological target for type 2 diabetes. The subsequent text mining with a unique query to identify suppressors but not activators of STAT3 revealed the ERK2/STAT3 pathway as a novel diabetes target. The description of ERK2 inhibitors as diabetes target had not been found in our text mining research at present. The mechanism-based peptide inhibitor for ERK2 was identified using the knowledge of the KIM sequence, which ha...
The uncoupling protein (UCP) is a proton/anion transporter found in the inner mitochondrial membrane of brown adipocyte. Although UCP has nor been detected in mitochondria from any other tissue, it shares structural and catalytic properties with several other mitochondrial carrier proteins. Although UCP was discovered only recently it is one of the most extensively studied mitochondrial carrier proteins.More recently, the mouse, rat, and human genes encoding for UCP have been isolated and sequenced. The availability of these various tools has led to several significant observations. UCP gene expression is strongly controlled at the level of transcription by signals that are activated after the stimulation of brown adipocytes by norepinephrine. The comparison of UCP gene with the genes encoding the adenine nucleotide translocator revealed the existence of structural and evolutionary homologies. Moreover, ...
This book examines the applications of Monte Carlo (MC) calculations in therapeutic nuclear medicine, from basic principles to computer implementations of software packages and their applications in radiation dosimetry and treatment planning. It is written for nuclear medicine physicists and physicians as well as radiation oncologists, and can serve as a supplementary text for medical imaging, radiation dosimetry and nuclear engineering graduate courses in science, medical and engineering faculties. With chapters is written by recognised authorities in that particular field, the book covers the entire range of MC applications in therapeutic medical and health physics, from its use in imaging prior to therapy to dose distribution modelling targeted radiotherapy. The contributions discuss the fundamental concepts of radiation dosimetry, radiobiological aspects of targeted radionuclide therapy and the ...
This study emphasizes the need for a systematic and in-depth connection between the progress in quantum theory of energetic ion collisions and applications to hadron therapy. Scattering theory for fast ion beams has reached its stage of development where accurate and robustly applicable methodologies can advantageously be exported to applied fields such as space research, fusion energy program, medicine, etc. In particular, distorted wave collision theories at high energies readily provide total, partial and fully differential cross sections for inelastic collisions of ionic projectiles with any target system. By numerous and thorough testings, such theoretical cross sections were found to exhibit excellent agreement with experimental data on atomic targets. Adequate extensions of these me...
Antibodies directed against markers on cancer cells are gaining in importance for the purpose of targeting diagnostic and therapeutic agents. In the past, this approach has had very limited success principally because the classical methods for producing antibodies from blood serum of animals immunized with cancer cells or extracts were unsatisfactory. The situation has changed dramatically since 1975 following the design of procedures for 'immortalizing' antibody-producing cells (lymphocytes) by fusing them with cultured myeloma cells to form hybridomas which continuously secrete antibodies. Since these hybridomas produce antibodies coded for by a single antibody-producing cell, the antibodies are called monoclonal. Building on these advances in biomedical research, it is now possible to reproducibly manufacture monoclonal antibodies on a scale suitable for use in cancer detection and therapy.
Hepatocellular carcinoma (HCC) represents a major health problem as it afflicts an increasing number of patients worldwide. Albeit most of the risk factors for HCC are known, this is a deadly syndrome with a life expectancy at the time of diagnosis of less than 1?year. Definition of the molecular principles governing the neoplastic transformation of the liver is an urgent need to facilitate the clinical management of patients, based on innovative methods to detect the disease in its early stages and on more efficient therapies. In the present study, we have combined the analysis of a murine model and human samples of HCC to identify genes differentially expressed early in the process of hepatocarcinogenesis, using a microarray-based approach. Expression of 190 genes was impaired in murine ...
Purpose : To detect differentially expressed genes in the patients with uterine cervical cancer during the radiation therapy. Materials and Methods : In patients with biopsy proven uterine cervical cancer, we took a tumor tissue just before radiation therapy and at 40 minutes after external irradiation of 1.8 Gy. Total RNAs isolated from non-irradiated and irradiated tumor tissue samples were analyzed using the differential-display reverse transcription-polymerase chain reaction (DDRT-PCR). Complementary DNA (cDNA) fragments corresponding to differentially expressed messenger RNAs(mRNAs) were eluted, and cloned. The differential expression of the corresponding mRNAs was confirmed by reverse northern blot. Differentially expressed cDNA bands were sequenced. Nucleotide sequence data were analyzed in the Gene Bank and EMBL databases via the BLAST network server to identify homologies to known ...
Our inability to associate distant regulatory elements with the genes that they regulate has largely precluded their examination for sequence alterations contributing to human disease. One major obstacle is the large genomic space surrounding targetedgenes in which such elements could potentially reside. In order to delineate gene regulatory boundaries we used whole-genome human-mouse-chicken (HMC) and human-mouse-frog (HMF) multiple alignments to compile conserved blocks of synteny (CBS), under the hypothesis that these blocks have been kept intact throughout evolution at least in part by the requirement of regulatory elements to stay linked to the genes that they regulate. A total of 2,116 and 1,942 CBS>200 kb were assembled for HMC and HMF respectively, encompassing 1.53 and 0.86 Gb of human sequence. To support the existence of complex long-range regulatory domains ...
Caffeine and related xanthines were identified as potent stimulators for the bacterial cellulose production in A. xylinum. These compounds are present in several plants whose infusions are useful as culture-medium supplements for this acetobacterium. The proposed target for these native purine-like inhibitory substances is the novel diguanyl nucleotide phosphodiesterase(s) that participates in the bacterial cellulogenic complex.
We describe the isolation and genetic characterization of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced mutations in the phage P22 mnt repressor gene cloned in plasmid pBR322. Mutations in the mnt repressor gene or its operator on this plasmid, pPY98, confer a tetracycline resistance phenotype, whereas the wild-type plasmid confers tetracycline sensitivity. Cells carrying pPY98 were briefly exposed to MNNG to give 20 to 40% survival and a 50- to 100-fold increase in tetracycline-resistant cells. DNA sequence analysis showed that 29 to 30 MNNG-induced mutations were GC-to-AT transitions and one was an AT-to-GC transition. About 80% of the mutations are in three hotspots. This mutation spectrum is consistent with the proposed mechanism of mutagenic action of MNNG, which involves mispairing of an alkylated base, O/sup 6/-methylguanine. The mnt gene may be a useful target for determining ...
The purpose of this study was to investigate whether the expression of specific genes in peripheral blood can be used as surrogate marker(s) to detect and distinguish target organ toxicity induced by chemicals in rats. Rats were intraperitoneally administered a single, acute dose of a well-established hepatotoxic (acetaminophen) or a neurotoxic (methyl parathion) chemical. Administration of acetaminophen (AP) in the rats resulted in hepatotoxicity as evidenced from elevated blood transaminase activities. Similarly, administration of methyl parathion (MP) resulted in neurotoxicity in the rats as evidenced from the inhibition of acetyl cholinesterase activity in their blood. Administration of either chemical also resulted in mild hematotoxicity in the rats. Microarray analysis of the global ...
Pork identification in four types of food products, which are sausages and the casings, bread and biscuits, using species-specific polymerase chain reaction (PCR) detection of a conserved region in the mitochondrial (mt) 12S ribosomal RNA (rRNA) gene was developed. Genomic DNA of the food products were successfully extracted except for the casing samples, where no genomic DNA was detected. The extracted genomic DNA was then subjected to PCR amplification targeting the specific regions of the 12S rRNA gene. The genomic DNA from the food products were found to be of good quality and produced clear PCR products on the amplification of 12S rRNA gene of 387 base pairs (bp) from pork species. The species-specific PCR identification yielded excellent results for identification of pork derivatives...
Background In chordates, retinoid metabolism is an important target of short-chain dehydrogenases/reductases (SDRs). It is not known whether SDRs play a role in retinoid metabolism of protostomes, such as Drosophila melanogaster. Methods Drosophila genome was searched for genes encoding proteins with ?50% identity to human retinol dehydrogenase 12 (RDH12). The corresponding proteins were expressed in Sf9 cells and biochemically characterized. Their phylogenetic relationships were analyzed using PHYLIP software. Results A total of six Drosophila SDR genes were identified. Five of these genes are clustered on chromosome 2 and one is located on chromosome X. The deduced proteins are 300 to 406 amino acids long and are associated with microsomal membranes. They recognize all-trans-retinaldehyd...
Transgenic plants offer advantages for biomolecule production because plants can be grown on a large scale and the recombinant macromolecules can be easily harvested and extracted. We introduced an Aspergillus phytase gene into canola (Brassica napus) (line 9412 with low erucic acid and low glucosinolates) by Agrobacterium-mediated transformation. Phytase expression in transgenic plant was enhanced with a synthetic phytase gene according to the Brassica codon usage and an endoplasmic reticulum (ER) retention signal KDEL that confers an ER accumulation of the recombinant phytase. Secretion of the phytase to the extracellular fluid was also established by the use of the tobacco PR-S signal peptide. Phytase accumulation in mature seed accounted for 2.6% of the total soluble proteins. The enzy...
Recent technological developments have facilitated intensified searches for genetic markers under selection in nonmodel species. Here, we present an approach for the identification of candidate gene variation in nonmodel organisms. We report on the characterization of 82 single nucleotide polymorphisms (SNPs) and on the development of a specific genotyping assay for 30 SNPs in 18 candidate genes for growth and reproduction in Atlantic cod (Gadus morhua). These markers can be used for scanning natural populations for signatures of selection in both contemporary and archived historical samples, for example in retrospective studies assessing the effects of environmental changes, such as increasing temperatures, and selection imposed by high fishing pressure. Furthermore, these gene markers may be of interest to aquaculture, serving as a starting point for linking phenotypic traits important for productivity with genotypes and ...
This report concerns investigations in the title conducted by 8 groups of National Institute of Radiological Sciences (NIRS) during the period of 1998-2000. The groups are for investigation of: Effects of p53 tumor suppressor gene in radiation-induced leukemia, Role of atm-gene in dose rate effect of ionizing radiation, Function of DNA-dependent protein kinase catalytic subunit (DNA-PK{sub cs}), Functional complementation of radiation-sensitive mutant M10 cell line by human XRCC4 cDNA expression, Role of radiation-induced apoptosis in digital defects in embryonic mice, Functional analysis of S-phase specific novel nuclear protein NP95 by genetargeting, Role of chemokine in T cell development and lymphomagenesis, and establishment of production techniques of gene-modified mice using embryonic stem cells for genetic analysis of radiation-sensitive genes. The ...
Patients with acute myocardial infarction (AMI) and diabetes mellitus, as well as patients admitted with elevated blood glucose without known diabetes, have impaired outcome. Therefore intensive glucose-lowering therapy with insulin (IGL) has been proposed in diabetic or hyperglycaemic patients and has been shown to improve survival and reduce incidence of adverse events. The current manuscript provides an overview of randomised controlled trials investigating the effect of IGL. Furthermore, systematic glucose?insulin?potassium infusion (GIK) has been studied to improve outcome after AMI. In spite of positive findings in some early studies, GIK did not show any beneficial effects in recent clinical trials and thus this concept has been abandoned. While IGL targeted to achieve normoglycaemi...
Purpose: The aim of this study was to assess interinstitutional variations in planning for stereotactic body radiation therapy (SBRT) for lung cancer before the start of the Japan Clinical Oncology Group (JCOG) 0403 trial.Methods and Materials: Eleven institutions created virtual plans for four cases of solitary lung cancer. The created plans should satisfy the target definitions and the dose constraints for the JCOG 0403 protocol.Results: FOCUS/XiO (CMS) was used in six institutions, Eclipse (Varian) in 3, Cadplan (Varian) in one, and Pinnacle3 (Philips/ADAC) in one. Dose calculation algorithms of Clarkson with effective path length correction and superposition were used in FOCUS/XiO; pencil beam convolution with Batho power law correction was used in Eclipse and Cadplan; and collapsed co...
The low in vivo transduction efficiency of recombinant adeno-associated virus (rAAV) and the undesirably strong immunogenicity of adenovirus (rAdv) have limited their clinical utilization in cancer genetherapy. We have previously demonstrated that intratumoral injection of rAAV expressing a C-terminal polypeptide of human telomerase reverse transcriptase (rAAV-hTERTC27) effectively inhibits the growth of glioblastoma xenografts in nude mice. To further improve its efficacy, we combined rAAV-hTERTC27 with rAdv and investigated the efficiency of the cocktail vectors in vivo. At a nontherapeutic dose (1 x 108 plaque-forming units (PFUs)), rAdv-null and rAdv-hTERTC27 were equipotent in enhancing the therapeutic efficacy of rAAV-hTERTC27 (1.5 x 1011?v.g.), and complete tumor regression w...
The Myc oncoprotein is a potent inducer of cell growth, cell cycle progression, and apoptosis. While many direct Myc targetgenes have been identified, the molecular determinants of Myc’s transcriptional...Full Text Available
BackgroundEstrogen receptors alpha (ERα) and beta (ERβ) are transcription factors (TFs) that mediate estrogen signaling and define the hormone-responsive phenotype...Full Text Available
AIM: To evaluate the biological and clinical characteristics of miR-622 in gastric cancer.METHODS: We analyzed the expression of miR-622 in 57 pair matched gastric neoplastic and adjacent non-neoplastic...Full Text Available
Transdifferentiation of an individual's own cells into functional differentiated cells to replace an organ's lost function would be a personalized approach to therapeutics. In this two part series, we will describe the progress toward establishing functional transdifferentiated adrenal cortical cells. In this article (Part 2), we describe the disorders of the adrenal cortex, therefore establishing why there is the need for personalized cell-based therapy for individuals with these disorders. We then present our pilot studies of cell transdifferentiation toward an adrenal cortical fate using genes described in the first article of this pair (Part 1).
The low in vivo transduction efficiency of recombinant adeno-associated virus (rAAV) and the undesirably strong immunogenicity of adenovirus (rAdv) have limited their clinical utilization in cancer genetherapy. We have previously demonstrated that intratumoral injection of rAAV expressing a C-terminal polypeptide of human telomerase reverse transcriptase (rAAV-hTERTC27) effectively inhibits the growth of glioblastoma xenografts in nude mice. To further improve its efficacy, we combined rAAV-hTERTC27 with rAdv and investigated the efficiency of the cocktail vectors in vivo. At a nontherapeutic dose (1 x 10(8) plaque-forming units (PFUs)), rAdv-null and rAdv-hTERTC27 were equipotent in enhancing the therapeutic efficacy of rAAV-hTERTC27 (1.5 x 10(11) v.g.), and complete tumor regression was achieved in 25% of the treated animals. Importantly, the combination of rAAV-hTERTC27 and a therapeutic dose (2.5 x 10(9) PFU) of rAdv-hTERTC27 significantly ...
The purpose of this study was to compare 2 adaptive radiotherapy strategies with helical tomotherapy. A patient having mesothelioma with mediastinal nodes was treated using helical tomotherapy with pretreatment megavoltage CT (MVCT) imaging. Gross tumor volumes (GTVs) were outlined on every MVCT study. Two alternatives for adapting the treatment were investigated: (1) keeping the prescribed dose to the targets while reducing the dose to the OARs and (2) escalating the target dose while maintaining the original level of healthy tissue sparing. Intensity modulated radiotherapy (step-and-shoot IMRT) and 3D conformal radiotherapy (3DCRT) plans for the patient were generated and compared. The primary lesion and nodal mass regressed by 16.2% and 32.5%, respectively. Adapted GTVs and reduced plan...
A novel compact CT-guided intensity modulated proton radiotherapy (IMPT) system is described. The system is being designed to deliver fast IMPT so that larger target volumes and motion management can be accomplished. The system will be ideal for large and complex target volumes in young patients. The basis of the design is the dielectric wall accelerator (DWA) system being developed at the Lawrence Livermore National Laboratory (LLNL). The DWA uses fast switched high voltage transmission lines to generate pulsed electric fields on the inside of a high gradient insulating (HGI) acceleration tube. High electric field gradients are achieved by the use of alternating insulators and conductors and short pulse times. The system will produce individual pulses that can be varied in intensity, energy and spot width. The IMPT planning system will optimize delivery characteristics. The system will be capable of being sited in a conventional linac vault ...
Glioblastoma multiforme is the most aggressive form of human brain tumor, which has no effective cure. Previously, we have demonstrated that overexpression of the C-terminal fragment of the human telomerase reverse transcriptase (hTERTC27) inhibits the growth and tumorigenicity of human cervical cancer HeLa cells. In this study, the therapeutic effect and molecular mechanisms of hTERTC27-mediated cancer genetherapy were further explored in vivo in established human glioblastoma xenografts in nude mice. We showed that intratumoral injection of adeno-associated virus carrying hTERTC27 (rAAV-hTERTC27) is highly effective in reducing the growth of the subcutaneously transplanted glioblastoma tumors. Histological analyses showed that rAAV-hTERTC27 treatment leads to profound necrosis, apoptosis, infiltration of polymorphonuclear neutrophils and reduced microvessel density in the tumor samples. To study the molecular mechanism of ...
Anxiety disorders are a highly prevalent and disabling class of psychiatric disorders. This review focuses on new directions in neurobiological research and implications for the development of novel psychopharmacological treatments. Neuroanatomical and neuroimaging research in anxiety disorders has centered on the role of the amygdala, reciprocal connections between the amygdala and the prefrontal cortex, and, most recently, alterations in interoceptive processing by the anterior insula. Anxiety disorders are characterized by alterations in a diverse range of neurochemical systems, suggesting ample novel targets for drug therapies. Corticotropin-releasing factor (CRF) concentrations are elevated in a subset of anxiety disorders, which suggests the potential utility of CRF receptor antagoni...
Dyspnea is the most distressing symptom experienced by those suffering from advanced stages of chronic obstructive pulmonary disease (COPD). Activity-related dyspnea in COPD is multifactorial but is associated with increased central neural drive, impaired dynamic respiratory mechanics and abnormal respiratory muscle function. Each of these components can potentially be targeted for pharmacotherapy. Recent advances in the pharmacotherapy of COPD include the development of new long-acting bronchodilators which, when combined, provide sustained improvements in dyspnea. Additionally, novel applications of older therapies such as opiates, furosemide, helium-oxygen, and statins show early promise as dyspnea-relieving interventions in COPD. Effective pharmacological manipulation of the affective ...
... or she will start intensive rehabilitation. This includes physical therapy and occupational therapy. Physical and occupational therapies aim at strengthening the remaining ...
Receptor interacting protein 140 (RIP140) is a coregulator for numerous nuclear receptors and transcription factors and primarily exerts gene-repressive activities on various targetgenes. We previously identified a spectrum of posttranslational modifications on RIP140 that augment its property and biological activity. In T(3)-triggered biphasic regulation of cellular retinoic acid binding protein 1 (Crabp1) gene along the course of fibroblast-adipocyte differentiation, we found TRAP220(MED1) critical for T(3)-activated chromatin remodeling whereas RIP140 essential for T(3)-repressive chromatin remodeling of this gene promoter. In this current study, we aim to examine whether and how RIP140 replaces TRAP220(MED1) on the CrabpI promoter in differentiating adipocyte cultures. We find increasing recruitment of RIP140 to this promoter, with corresponding reduction in TRAP220(MED1) ...
Hox genes encode a family of transcriptional regulators that operate differential developmental programs along the anteroposterior axis of bilateral animals. Regulatory changes affecting Hox gene expression are believed to have been crucial for the evolution of animal body plans. In Drosophila melanogaster, Hox expression is post-transcriptionally regulated by microRNAs (miRNAs) acting on target sites located in the 3' untranslated regions (3'UTRs) of Hox mRNAs. Notably, recent work has shown that during D. melanogaster development Hox genes produce mRNAs with variable 3'UTRs (short and long forms) in different sets of tissues as a result of alternative polyadenylation; importantly, Hox short and long 3'UTRs contain very different target sites for miRNAs. Here, we use a computational approach to explore the evolution of Hox 3'UTRs treated with especial regard to miRNA regulation. ...
Short synthetic single-stranded oligodeoxyribonucleotides (ssODNs) can be used to introduce subtle modifications into the genome of mouse embryonic stem cells (ESCs). We have previously shown that effective application of ssODN-mediated genetargeting in ESC requires (transient) suppression of DNA mismatch repair (MMR). However, whereas transient down-regulation of the mismatch recognition protein MSH2 allowed substitution of 3 or 4 nucleotides, 1 or 2 nucleotide substitutions were still suppressed. We now demonstrate that single- or dinucleotide substitution can effectively be achieved by transient down-regulation of the downstream MMR protein MLH1. By exploiting highly specific real-time PCR, we demonstrate the feasibility of substituting a single basepair in a non-selectable gene. Howev...
Nineteen fungal strains having an ability to oxidize elemental sulfur in mineral salts medium were isolated from deteriorated sandstones of Angkor monuments. These fungi formed clearing zone on agar medium supplemented with powder sulfur due to the dissolution of sulfur. Representative of the isolates, strain THIF01, was identified as Fusarium solani on the basis of morphological characteristics and phylogenetic analyses. PCR amplification targeting 16S rRNA gene and analyses of full 16S rRNA gene sequence indicated strain THIF01 harbors an endobacterium Bradyrhizobium sp.; however, involvement of the bacterium in the sulfur oxidation is still unclear. Strain THIF01 oxidized elemental sulfur to thiosulfate and then sulfate. Germination of the spores of strain THIF01 was observed in a liqui...
To more accurately measure fluorescent signals from microarrays, we calibrated our acquisition and analysis systems by using groundtruth samples comprised of known quantities of red and green gene-specific DNA probes hybridized to cDNA targets. We imaged the slides with a full-field, white light CCD imager and analyzed them with our custom analysis software. Here we compare, for multiple genes, results obtained with and without preprocessing (alignment, color crosstalk compensation, dark field subtraction, and integration time). We also evaluate the accuracy of various image processing and analysis techniques (background subtraction, segmentation, quantitation and normalization). This methodology calibrates and validates our system for accurate quantitative measurement of microarrays. Specifically, we show that preprocessing the images produces results significantly closer to the known ground-truth for these samples.
Please cite this paper as: Ectopic mineralization of connective tissue in Abcc6-/- mice: effects of dietary modifications and a phosphate binder - a preliminary study. Experimental Dermatology 2008; 17: 203-207. Abstract: Pseudoxanthoma elasticum (PXE), a heritable multisystem disorder, is caused by mutations in the ABCC6 gene. We have developed a murine model for PXE by targeted inactivation of the corresponding mouse gene. A feature of this mouse model is ectopic mineralization of connective tissue capsule surrounding the bulb of vibrissae. This study was designed to investigate the effect of dietary sevelamer hydrochloride (Renagel), a phosphate binder, and specific mineral modifications on ectopic mineralization of connective tissue in Abcc6-/- mice. Three groups were fed a specific di...
Data are presented to support the hypothesis that the initial step in the morphologic transformation of irradiated rodent (BALB/3T3) cells is a frequent cellular event involving a large fraction of the irradiated population. This process appears to involve DNA damage, but not to represent a targeted mutation in specific structural gene(s). Morphologic transformation and immortalization appear to be distinct steps in the overall process of transformation. In contradistinction to rodent cells, immortalization is a very rare event in human diploid cells which is induced at extremely low frequencies. The hypothesis is presented that immortality develops among clones of cells bearing stable chromosomal rearrangements which emerge during the proliferation of a population of radiation damaged cells.
In radiation therapy with hadron beams, conformal irradiation to a tumour can be achieved by using the properties of incident ions such as the high dose concentration around the Bragg peak. For the effective utilization of such properties, it is necessary to evaluate the volume irradiated with hadron beams and the deposited dose distribution in a patient's body. Several methods have been proposed for this purpose, one of which uses the positron emitters generated through fragmentation reactions between incident ions and target nuclei. In the previous paper, we showed that the maximum likelihood estimation (MLE) method could be applicable to the estimation of beam end-point from the measured positron emitting activity distribution for mono-energetic beam irradiations. In a practical treatment, a spread-out Bragg peak (SOBP) beam is used to achieve a uniform biological dose distribution in the whole target volume. ...
Purpose: The aim of this study was to assess interinstitutional variations in planning for stereotactic body radiation therapy (SBRT) for lung cancer before the start of the Japan Clinical Oncology Group (JCOG) 0403 trial. Methods and Materials: Eleven institutions created virtual plans for four cases of solitary lung cancer. The created plans should satisfy the target definitions and the dose constraints for the JCOG 0403 protocol. Results: FOCUS/XiO (CMS) was used in six institutions, Eclipse (Varian) in 3, Cadplan (Varian) in one, and Pinnacle3 (Philips/ADAC) in one. Dose calculation algorithms of Clarkson with effective path length correction and superposition were used in FOCUS/XiO; pencil beam convolution with Batho power law correction was used in Eclipse and Cadplan; and collapsed cone convolution superposition was used in Pinnacle3. For the target volumes, the overall coefficient of variation was 16.6%, and the ...
A technique capable of measuring the electron energy fluence spectra in a scattering medium was designed. These measurements were performed by setting a bremsstrahlung conversion target on the surface of a phantom, at an intermediate depth, and at a depth equal to electron mean range. The bremsstrahlung produced by the deceleration of electrons in the target was passed through an air channel in the phantom and passed forward by a pinhole collimator into a Na(Tl) detector. The measured pulse height data were unfolded to correct for the distortion of the spectrometer system by using the FORIST unfolding code. The unfolded bremsstrahlung spectra represent the electron energy fluence spectra convolution with the bremsstrahlung produced in the target. To generate the electron energy fluence spectra, the unfolded bremsstrahlung spectra were deconvoluted by using the MAZE2 unfolding code. CYLTRAN, a coupled electron-photon Monte ...
The neuronal nicotinic acetylcholine receptor {alpha}7 subunit is a member of a family of ligand-gated ion channels, and is the only subunit know to bind {alpha}-bungarotoxin in mammalian brain. {alpha}-Bungarotoxin binding sites are known to be more abundant in the hippocampus of mouse strains that are particularly sensitive to nicotine-induced seizures. The {alpha}7 receptor is highly permeable to calcium, which could suggest a role in synaptic plasticity in the nervous system. Auditory gating deficiency, an abnormal response to a second auditory stimulus, is characteristic of schizophrenia. Mouse strains that exhibit a similar gating deficit have reduced hippocampal expression of the {alpha}7 subunit. We have cloned and sequenced the full length cDNA for the mouse {alpha}7 gene (Acra-7) and characterized its gene structure. The murine {alpha}7 shares amino acid identity of 99% and 93% with the rat and human {alpha}7 subunits, respectively. ...
Two candidate small interfering RNAs (siRNAs) corresponding to severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike gene were designed and in vitro transcribed to explore the possibility of silencing SARS-CoV S gene. The plasmid pEGFP-optS, which contains the codon-optimized SARS-CoV S gene and expresses spike-EGFP fusion protein (S-EGFP) as silencing target and expressing reporter, was transfected with siRNAs into HEK 293T cells. At various time points of posttransfection, the levels of S-EGFP expression and amounts of spike mRNA transcript were detected by fluorescence microscopy, flow cytometry, Western blot, and real-time quantitative PCR, respectively. The results showed that the cells transfected with pEGFP-optS expressed S-EGFP fusion protein at a higher level compared with those transfected with pEGFP-S, which contains wildtype SARS-CoV spike gene ...
The liver is a primary target of growth hormone (GH). GH signals are mediated by the transcription factor signal transducer and activator of transcription 5 (STAT5). Here, we focus on recent discoveries about the role of GH-STAT5 signaling in hepatic physiology and pathophysiology. We discuss roles of the GH-STAT5 axis in body growth, lipid metabolism, and the cell cycle pertaining to hepatosteatosis, fibrosis, and hepatocellular carcinoma. Finally, we discuss recent discoveries about the role of GH-STAT5 in sex-specific gene expression and bile acid, steroid, and drug metabolism.
Neurotensin (NT) and its high affinity receptor (NTR1) are involved in several neoplastic processes. Thus, NT-based radiopharmaceuticals are potential tracers for targeted diagnosis and therapy of NTR-positive tumours. A new analogue based on NT(8-13), NT-XIX, with the three enzymatic cleavage sites stabilised, was synthesised and tested. The synthesis was performed by Boc strategy. Labelling with "9"9"mTc/"1"8"8Re was performed using the tricarbonyl technique. Metabolic stability was tested in vitro and in vivo. NT-XIX was further characterised in vitro in HT-29 cells and in vivo in nude mice with HT-29 xenografts. NT-XIX showed much longer half-lives than non-stabilised analogues. Binding to NTR1 was highly specific, although the affinity was lower than that of natural NT. Bound activity rapidly internalised into HT-29 cells and 50% remained trapped after 24 h. In the time-course biodistribution, the highest uptake was found in the tumour at ...
In the treatment of prostatic cancer using a newly proposed intermittent multiportal therapy (DIMT), acute reactions, change in tumor marker levels, and complications more than 6 months after treatment were evaluated. From June 1989 to September 1990, 26 patients with prostatic cancer (stage A2, 3 patients; B, 9; C, 2; D, 10; recurrence, 2) were treated. Fifteen patients were followed up for more than one year, with a mean period of 11.6 months. The treatment schedule is 52.5 Gy in 16 fractions in 4 weeks for radical treatment, and 30.0 Gy in 8 fractions in 2 weeks for palliative treatment. The 360 degree rotation about the patient was divided into 16 fractions, and 2 opposing fractions were used in one day as parallel opposed portals to treat the target volume. The fractions were serially treated one per day, so that 8 treatment days produced a total dose of distribution similar to that for conventional conformational ...
The feasibility of containing genetically engineered bacteria with enhanced dehalogenating properties for in situ bioremediation was investigated. (1) An agarose matrix microbead protocol and a detection system for contained microorganisms or DNA were developed. Multiplex Polymerase Chain Reaction (PCR) allowed tracking of a consortium of encapsulated organisms or several genetargets from a single species. Gene sequences encoding the enzymes responsible for initiating the biodegradation of toluene, octane, and 2,4-D were detected by multiplex PCR and nucleic acid probes from similar to 1-10 biodegradative cells/g soil. Improved DNA extraction methods resulted in PCR reactions detecting similar to 6 cells/g soil. (2) The pcpB gene (for the broad-spectrum detoxicant pentachlorophenol (PCP) hydroxylase) isolated from Flavobacterium sp. strain ATCC 39723 was used in attempts to develop an improved ...
BACKGROUND Accumulating evidence suggests that various epigenetic aberrations play definite roles in the pathogenesis of endometriosis. We investigated the histone acetylation status in endometriosis and the application of the histone deacetylase inhibitors (HDACIs) for the treatment of endometriosis. METHODS The levels of acetylated histones in the endometriotic cyst stromal cells (ECSCs) and normal endometrial stromal cells (NESCs) were evaluated. The effects of the HDACIs on cell proliferation, the cell cycle, apoptosis of ECSCs and NESCs, and the expression of genes related to these cellular events were investigated. The effects of HDACIs on histone acetylation in chromatin of the promoter region of the cell cycle regulatory genes in ECSCs were also investigated. RESULTS The acetylated histone levels were significantly lower in ECSCs than in NESCs (P endometriosis and that HDACIs reactivated epigenetically silenced ...
Aims: The present study explored the integrative effect of genes encoding methadone pharmacokinetic and pharmacodynamic pathways on methadone maintenance doses in Han Chinese Patients. Materials & methods: Genomic DNA was extracted from 321 opioid-dependent patients and 202 healthy controls, and realtime-PCR and PCR-RFLP were conducted to determine the genotypes. Results: Pair-wise comparisons revealed that carriers of the variants ABCB1 3435C>T or CYP2B6 516G>T alleles were more likely to require a higher methadone dose than noncarriers (both p G or 939C>T allele had a two-fold chance of requiring a lower methadone dose than noncarriers (p = 0.001). Proportional odds regression with adjustment of cofactors demonstrated that ...
The work scope of 'Biological Research for the Radiation Protection' had contained the research about ornithine decarboxylase and its controlling proteins, thioredoxin, peroxiredoxin, S-adenosymethionine decarboxylase, and glutamate decarboxylase 67KD effect on the cell death triggered ionizing radiation and H_2O_2(toxic agents). In this study, to elucidate the role of these proteins in the ionizing radiation (or H_2O_2)-induced apoptotic cell death, we utilized sensesed (or antisensed) cells, which overexpress (or down-regulate) RNAs associated with these proteins biosynthesis, and investigated the effects of these genes on the cytotoxicity caused by ionizing radiation and H_2O_2(or paraquat). We also investigated whether genisteine(or thiamine) may enhance the cytotoxic efficacy of tumor cells caused by ionizing radiation (may enhance the preventing effect radiation or paraquat-induced damage) because such compounds are able to potentiate the cell-killing or cell ...
Background and purpose: the recent RTOG guidelines for future clinical developments in gynecologic malignancies included the investigation of dose escalation in the paraaortic (PO) region which is, however, very difficult to target due to the presence of critical organs such as kidneys, liver, spinal cord, and digestive structures. The aim of this study was to investigate intensity-modulated radiotherapy's (IMRT) possibilities of either increasing, in a safe way, the dose to 50-60 Gy in case of macroscopic disease or decreasing the dose to organs at risk (OR) when treatment is given in an adjuvant setting. Material and methods: the dosimetric charts of 14 patients irradiated to the PO region at the department of radiation oncology, university hospital of Liege, Belgium, in 2000 were analyzed in order to compare six-field conformal external-beam radio-therapy (CEBR) and five-beam IMRT approaches. Both CEBR and IMRT investigations were planned to ...
Megavoltage photon intensity-modulated radiation therapy (IMRT) is typically used in the treatment of prostate cancer at our institution. Approximately 1% to 2% of patients with prostate cancer have hip prostheses. The presence of the prosthesis usually complicates the planning process because of dose perturbation around the prosthesis, radiation attenuation through the prosthesis, and the introduction of computed tomography artifacts in the planning volume. In addition, hip prostheses are typically made of materials of high atomic number, which add uncertainty to the dosimetry of the prostate and critical organs in the planning volume. When the prosthesis is bilateral, treatment planning is further complicated because only a limited number of beam angles can be used to avoid the prostheses. In this case study, we will report the observed advantages of using noncoplanar beams in the delivery of IMRT to a prostate cancer patient with bilateral hip prostheses. The ...
Electron beam therapy of lesions such as cutaneous metastatic carcinoma and reticulum cell sarcoma is performed via multiple portals for a wide irradiation field. However, the dose distribution in border areas is generally uneven, resulting in hot and cold dose areas depending on the intervals of the portals. We performed electron irradiation by the pendulum technique, especially on curved areas, and evaluated the technique in various respects. Pendulum electron beam irradiation is indicated when the length of the cone must be reduced in order to deliver the target volume near the skin surface as well as to avoid the occurrence of hot spots deep in the body. We prepared a 15cm rotating cone by cutting a 30cm fixed irradiation cone. The modification posed no disadvantages in terms of extent and flatness of the beam, or stability during rotation. After determining the relationship between the rotation speed and the dose, the technique was ...
Glycyrrhiza glabra root is one of the common traditional Chinese medicines and used as flavoring and sweetening agents for tobaccos, chewing gums, candies, toothpaste and beverages. While glycyrrhizin is one of the main components in the extract of G. glabra root and has been characterized, the other components have not been well characterized. The mechanism of growth activation of breast cancer MCF-7 cells, including the activation of Erk1/2 and Akt, and the transcriptional regulation of estrogen-responsive genes, was examined by means of sulforhodamine B, luciferase reporter gene, real-time RT-PCR and Western blotting assays after the induction of the cells with the extract of G. glabra root. The extract has similar activity to that induced by 17beta-estradiol (E(2)), although glycyrrhizin did not show such an activity. Moreover, the estrogen receptor alpha-dependent neurite outgrowth induced by the extract was similar to that by E(2), ...
The GntR-like protein NorG has been shown to affect Staphylococcus aureus genes involved in the resistance to quinolones and ?-lactams, such as those encoding the NorB and AbcA transporters. To identify the targetgenes regulated by NorG, we carried out transcriptional profiling assays using S. aureus RN6390 and its isogenic norG::cat mutant. Our data showed that NorG positively affected the transcription of global regulators mgrA, arlS, and sarZ. The three putative drug efflux pump genes most positively affected by NorG were the NorB efflux pump (5.1-fold), the MmpL-like protein SACOL2566 (5.2-fold), and the BcrA-like drug transporter SACOL2525 (5.7-fold). The S. aureus predicted MmpL protein showed 53% homology with the MmpL lipid transporter of Mycobacterium tuberculosis, and the putative SACOL2525 protein showed 87% homology with the bacitracin drug transporter BcrA of Staphylococcus hominis. Two ...
To evaluate the role of phytochelatins and metallothioneins in heavy metal tolerance of black mangrove Avicennia germinans, 3-month-old seedlings were exposed to cadmium or copper for 30 h, under hydroponic conditions. Degenerate Mt2 and PCS primers were synthesized based on amino acid and nucleotide alignment sequences reported for Mt2 and PCS in other plant species found in GenBank. Total RNA was isolated from A. germinans leaves and two partial fragments of metallothionein and phytochelatin synthase genes were isolated. Gene expression was evaluated with reverse transcripatase-polymerase chain reaction (RT-PCR) amplification technique. Temporal analysis showed that low Cd{sup 2+} and Cu{sup 2+} concentrations caused a slight (but not significant) increase in AvMt2 expression after a 16 h exposure time, while AvPCS expression showed a significant increase under the same conditions but only after 4 h. Results strongly suggest that the rapid ...
To evaluate the role of phytochelatins and metallothioneins in heavy metal tolerance of black mangrove Avicennia germinans, 3-month-old seedlings were exposed to cadmium or copper for 30 h, under hydroponic conditions. Degenerate Mt2 and PCS primers were synthesized based on amino acid and nucleotide alignment sequences reported for Mt2 and PCS in other plant species found in GenBank. Total RNA was isolated from A. germinans leaves and two partial fragments of metallothionein and phytochelatin synthase genes were isolated. Gene expression was evaluated with reverse transcripatase-polymerase chain reaction (RT-PCR) amplification technique. Temporal analysis showed that low Cd"2"+ and Cu"2"+ concentrations caused a slight (but not significant) increase in AvMt2 expression after a 16 h exposure time, while AvPCS expression showed a significant increase under the same conditions but only after 4 h. Results strongly suggest that the rapid increase ...
Abstract Male infertility continues to be a clinical challenge of increasing significance. While male factors such as decreased semen quality are responsible for 25% of all infertility issues, the etiology of suboptimal semen quality is poorly understood. Many physiological, environmental, and genetic factors have been implicated, including oxidative stress. Oxidative stress is induced by reactive oxygen species (ROS), or free radicals, and although ROS are required for critical aspects of sperm function, excessive levels of ROS can negatively impact sperm quality. The origin of ROS generation, and the etiologies of increased ROS in men with suboptimal sperm quality have only recently been elucidated, offering multiple targets for potential therapy. Here, we present a critical review of th...
Cancer cells recruit monocytes, macrophages and other inflammatory cells by producing abundant chemoattractants and growth factors, such as macrophage colony-stimulating factor (M-CSF/CSF-1) and monocyte chemoattractant protein-1 (MCP-1/CCL2), to promote tumor growth and dissemination. An understanding of the mechanisms that target cancer cells and regulate tumor microenvironment is essential in designing anticancer therapies. Here, we showed that serum amyloid-A (SAA) and cathelicidin (LL-37) stimulated M-CSF and MCP-1 expression with or without lipopolysaccharide (LPS) administration; conversely, lipoxin-A4 (LXA4) and annexin-A1 (ANXA1) inhibited LPS-induced M-CSF and MCP-1 production by human (HepG2) and mouse (H22) hepatocellular carcinoma cells (HCCs). The effects of LXA4, ANXA1, SAA ...
Positron emission tomography (PET) is the gold standard for non-invasive assessment of myocardial viability and allows accurate detection of coronary artery disease by assessment of myocardial perfusion. Magnetic resonance imaging (MRI) provides high resolution anatomical images that allow accurate evaluation of ventricular structure and function together with detection of myocardial infarction. Potential hybrid PET/MR tomography may potentially facilitate the combination of information from these imaging modalities in cardiology. Furthermore, the combination of anatomical MRI images with the high sensitivity of PET for detecting molecular targets may extent the application of these modalities to the characterization of atherosclerotic plaques and to the evaluation of angiogenetic or stem cell therapies, for example. This article reviews studies using MRI and PET in parallel to compare their performance in cardiac applications together with the ...
A computer-based beam dosimetry measurement system for boron neutron capture therapy provides accurate, sensitive, and rapid readout and recording of all beam dose components, epithermal and thermal neutron flux, and gamma-ray dose rate. This dosimetric system includes input from the characterization of the epithermal neutron beam developed at the Massachusetts Institute of Technology, actual BPA pharmacokinetic data from a specific human subject being irradiated, output of MacNCTPLAN, a treatment planning system developed by the authors group, and input from the five on-line beam detectors. The purpose of this system and associated readout systems is to ensure that the desired dose is delivered to the subject within acceptable dose tolerances, e.g., {+-}5% of the target dose, and that any perturbations in the neutron beam that may occur during irradiation can be rapidly evaluated and the appropriate measures taken.
A computer-based beam dosimetry measurement system for boron neutron capture therapy provides accurate, sensitive, and rapid readout and recording of all beam dose components, epithermal and thermal neutron flux, and gamma-ray dose rate. This dosimetric system includes input from the characterization of the epithermal neutron beam developed at the Massachusetts Institute of Technology, actual BPA pharmacokinetic data from a specific human subject being irradiated, output of MacNCTPLAN, a treatment planning system developed by the authors group, and input from the five on-line beam detectors. The purpose of this system and associated readout systems is to ensure that the desired dose is delivered to the subject within acceptable dose tolerances, e.g., #+-#5% of the target dose, and that any perturbations in the neutron beam that may occur during irradiation can be rapidly evaluated and the appropriate measures taken.
In Europe, the use of anti-EGFR monoclonal antibodies is restricted to Kirsten RAS (KRAS) wild-type colorectal tumors. Information on the KRAS status of the patients tumor is thus key for clinical practice; however, there is little guidance or definition on which KRAS mutations to assess and how to assess them. To ensure the consistency and the quality of KRAS test results in Europe, an interlaboratory control network needs to be set up. This pilot study aimed to identify the variables that need to be assessed in a quality control scheme and to provide a first assessment in a selected set of laboratories. Fourteen different tumor cases were circulated between 13 laboratories by a central laboratory acting as the referent for the mutation status determination. This study illustrated that of...
Radiolabeled lipiodol has been used for targeting liver cancer. We developed a lipiodol solution of {sup 188}Re-TDD (2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithiol) and investigated its feasibility for the treatment of liver cancer. The lipiodol solution of {sup 188}Re-TDD was well-retained in the lipiodol phase in vitro. After injection through the tail veins of mice, high lung-uptake was investigated which is evidence of embolizing activity. We also found high accumulation in hepatoma after injection through the hepatic arteries of hepatoma-bearing rats. In conclusion, the lipiodol solution of {sup 188}Re-TDD is a promising agent for liver cancer therapy.
Upconversion nanoparticles (UCNPs) with unique multi-photon excitation photoluminescence properties have recently been intensively explored as novel contrast agents for low-backgroundbiomedical imaging. In this work, we functionalize UCNPs with a polyethylene glycol (PEG) grafted amphiphilic polymer. The PEGylated UCNPs are loaded with a commonly used chemotherapy molecule, doxorubicin (DOX), by simple physical adsorption via a supramolecular chemistry approach for intracellular drug delivery. The loading and releasing of DOX from UCNPs are controlled by varying pH, with an increased drug dissociation rate in acidic environment, favorable for controlled drug release. Upconversion luminescence (UCL) imaging by a modified laser scanning confocal microscope reveals the time course of intracel...
A combination of sustained release (SR) naltrexone (32mg/day) and bupropion SR (360mg/day) plus behavioral counseling was evaluated for the treatment of smoking cessation and mitigation of nicotine withdrawal and weight gain. Thirty overweight or obese nicotine-dependent subjects were enrolled in a 24-week, open-label study; 85% and 63% completed 12 and 24weeks, respectively. The target quit date was Week 4. Week 4-12 continuous abstinence rate was 48%, 78% of subjects achieved CO 10ppm, serum cotinine decreased from 185 to 48mg/L, and tobacco use decreased from 129 to 14 cigarettes/week. Similar results were seen at Week 24. Body weight was essentially unchanged (Week 12: -0.1%; Week 24: +0.4%). Except for a transient significant increase 1week after the target quit date (p<0.05), nicotin...
Abstract The authors provide a survey of how images are used in radiation therapy to improve the precision of radiation therapy plans, and delivery of radiation treatment. In contrast...Full Text Available
Signal-to-noise-ratio (SNR) thresholds for microarray data analysis were experimentally determined with an oligonucleotide array that contained perfect match (PM) and mismatch (MM) probes based upon four genes from Shewanella oneidensis MR-1. A new SNR calculation, called signal to both standard deviations ratio (SSDR) was developed, and evaluated along with other two methods, signal to standard deviation ratio (SSR), and signal to background ratio (SBR). At a low stringency, the thresholds of SSR, SBR, and SSDR were 2.5, 1.60 and 0.80 with oligonucleotide and PCR amplicon as target templates, and 2.0, 1.60 and 0.70 with genomic DNA as target templates. Slightly higher thresholds were obtained at the high stringency condition. The thresholds of SSR and SSDR decreased with an increase in the complexity of targets (e.g., target types), and the presence of background DNA, and a ...
Full text: DNA rearrangement events leading to chromosomal aberrations are central to ionizing radiation-induced cell death. Although DNA double-strand breaks are probably the lesion that initiates formation of chromosomal aberrations, little is understood about the molecular mechanisms that generate and modulate DNA rearrangement. Examination of the sequences that flank sites of DNA rearrangement may provide information regarding the processes and enzymes involved in rearrangement events. Accordingly, we developed a method using inverse PCR that allows the detection and sequencing of putative radiation-induced DNA rearrangements in defined regions of the human genome. The method can detect single copies of a rearrangement event that has occurred in a particular region of the genome and, therefore, DNA rearrangement detection does not require survival and continued multiplication of the affected cell. Ionizing radiation-induced DNA rearrangements were detected in several different ...
BackgroundDespite an ever-improving understanding of the molecular biology of cancer, the treatment of most cancers has not changed dramatically in the past three decades and drugs that do not discriminate between tumor cells and normal tissues remain the mainstays of anticancer therapy. Since Hsp90 is typically involved in cell proliferation and survival, this is thought to play a key role in cancer, and Hsp90 has attracted considerable interest in recent years as a potential therapeutic target.MethodsWe focused on the interaction of Hsp90 with its cofactor protein p60/Hop, and engineered a cell-permeable peptidomimetic, termed "hybrid Antp-TPR peptide", modeled on the binding interface between the molecular chaperone Hsp90 and the TPR2A domain of Hop.ResultsIt was demonstrated that this designed hybrid Antp-TPR peptide inhibited the interaction of Hsp90 with the TPR2A domain, inducing cell death of breast, pancreatic, renal, lung, prostate, ...
PNAS-4, a novel pro-apoptotic gene activated during the early response to DNA damage, can inhibit proliferation via apoptosis when overexpressed in some tumor cells. Recent studies have indicated that honokiol can induce apoptosis, inhibit angiogenesis, and suppress tumor growth. In the present study, we investigated whether mouse PNAS-4 (mPNAS-4) could augment the apoptosis of tumor cells induced by honokiol in vitro, and whether the antiangiogenic activity of honokiol and induction of apoptosis by mPNAS-4 could work cooperatively to improve the antitumor efficacy in vivo. In vitro, mPNAS-4 inhibited proliferation of murine colorectal carcinoma CT26 and Lewis lung carcinoma LL2 cells through induction of apoptosis, and significantly augmented the apoptosis of CT26 and LL2 cells induced by honokiol. Compared with treatment with mPNAS-4 or honokiol alone, in vivo systemic administration of an expression plasmid encoding mPNAS-4 and low-dose honokiol significantly ...
A tk{sup +/-} mouse embryonic stem (ES) cell line, designated 1G2, has been created in which one allele of the thymidine kinase (tk) gene was inactivated by targeted homologous recombination. This line is an analog of the mouse lymphoma tk{sup +/-} L5178Y cell line, which is used widely to assess the mutagenicity of chemical agents. Treatment of 1G2 cells with the alkylating agent N-ethyl-N-nitrosourea (ENU) resulted in a dose-related increase in tribluorothymidine-resistant colonies. Mutant frequencies of 152 and 296 per 10{sup 6} cells were determined for 0.1 and 0.3 mg/ml doses of ENU, compared with a spontaneous mutant frequency of 15 per 10{sup 6} cells. The data indicate that tk{sup +/-} 1G2 ES cells may be useful for the creation of a transgenic mouse model for assessing in vivo mutation using an endogenous autosomal gene. 45 refs., 2 figs., 1 tab.
RNA interference (RNAi) plays an important role in regulating gene expression in eukaryotes. Previously, we generated Arabidopsis and tobacco plants expressing double-stranded RNA (dsRNA) targeting a cotton bollworm (Helicoverpa armigera) P450 gene, CYP6AE14. Bollworms fed on transgenic dsCYP6AE14 plants showed suppressed CYP6AE14 expression and reduced growth on gossypol-containing diet (Mao et?al., in Nat Biotechnol 25: 1307?1313, 2007). Here we report generation and analysis of dsRNA-expressing cotton (Gossypium hirsutum) plants. Bollworm larvae reared on T2 plants of the ds6-3 line exhibited drastically retarded growth, and the transgenic plants were less damaged by bollworms than the control. Quantitative reverse-transcription polymerase chain reaction (RT-PCR) showed that the CYP6AE1...
Abstract Many solute carrier transporters that interact with anticancer agents and contribute to their pharmacokinetics have been shown to be differentially upregulated in cancer cells as a result of adaptive response to altered nutritional requirements. This review focuses on pathophysiological function of membrane transporters responsible for the influx of physiological substances including oligopeptides, amino acids, and organic cations and anions, and summarizes the recent knowledge regarding mechanisms in their gene expressions. Broad substrate specificity of enhanced oligopeptide H+/peptide cotransporter 1 activity in cancer cells is useful for tumor tissue-specific delivery of chemotherapeutic agents and positron emission tomography diagnostic probes. Amino acid transporters such as...
Abstract Development of inhibitors and vaccines that mitigate rumen-derived methane by targeting methanogens relies on knowledge of the methanogens present. We investigated the composition of archaeal communities in the rumens of farmed sheep (Ovis aries), cattle (Bos taurus) and red deer (Cervus elaphus) using denaturing gradient gel electrophoresis (DGGE) to generate fingerprints of archaeal 16S rRNA genes. The total archaeal communities were relatively constant across species and diets, and were less variable and less diverse than bacterial communities. There were diet- and ruminant-species-based differences in archaeal community structure, but the same dominant archaea were present in all rumens. These were members of three coherent clades: species related to Methanobrevibacter ruminan...
The recent breakthrough in the generation of rat embryonic stem cells (rESCs) opens the door to application of genetargeting to create models for the study of human diseases. In addition, the in vitro differentiation system from rESCs into derivatives of three germ layers will serve as a powerful tool and resource for the investigation of mammalian development, cell function, tissue repair, and drug discovery. However, these uses have been limited by the difficulty of in vitro differentiation. The aims of this study were to establish an in vitro differentiation system from rESCs and to investigate whether rESCs are capable of forming terminal-differentiated cardiomyocytes. Using newly established rESCs, we found that embryoid body (EB)-based method used in mouse ESC (mESC) differentiation...
DNA methylation is considered as a potential cause of aberrations in regulation of gene expression during carcinogenesis. Therefore, changes in DNA methylation patterns may be targets for chemoprevention. In the present study, we investigated effects of all-trans retinoic acid (ATRA), vitamin D3, and resveratrol alone and in combination with adenosine analogues: 2-chloro-2'-deoxyadenosine (2CdA) and 9-beta-d-arabinosyl-2-fluoroadenine (F-ara-A), on methylation and expression of retinoic acid receptor beta 2 (RARbeta2) in MCF-7 and MDA-MB-231 breast cancer cell lines. Alterations in methylation and expression levels after treatment of cells with the tested compounds were evaluated by methylation-sensitive restriction analysis (MSRA) and real-time PCR, respectively. RARbeta2 promoter in the ...
Histone deacetylase (HDAC) inhibitors have been actively exploited as potential anticancer agents. To identify genetargets of HDAC inhibitors, we found that HDAC inhibitors such as sodium butyrate, scriptaid, apicidin and oxamflatin induced the expression of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a potential cyclooxygenase-2 (COX-2) antagonist and tumor suppressor, in a time and concentration dependent manner in A549 and H1435 lung adenocarcinoma cells. Detailed analyses indicated that HDAC inhibitors activated the 15-PGDH promoter-luciferase reporter construct in transfected A549 cells. A representative HDAC inhibitor, scriptaid, and its negative structural analog control, nullscript, were further evaluated at the chromatin level. Scriptaid but not nullscript induced a signific...
Optimization of nonviral gene delivery typically focuses on the design of particulate carriers that are endowed with desirable membrane targeting, internalization, and endosomal escape properties. Topographical control of cell transfectability, however, remains a largely unexplored parameter. Emerging literature has highlighted the influence of cell-topography interactions on modulation of many cell phenotypes, including protein expression and cytoskeletal behaviors implicated in endocytosis. Using high-throughput screening of primary human dermal fibroblasts cultured on a combinatorial library of microscale topographies, we have demonstrated an improvement in nonviral transfection efficiency for cells cultured on dense micropit patterns compared to smooth substrates, as verified with flow...
Background: Quantifying HIV levels in mucosal secretions is essential to study compartmentalized expression of HIV and facilitate development of intervention strategies to prevent disease progression and transmission. Objectives: To develop a sensitive, reliable, and cost-effective technique to quantify HIV from blood and vaginal secretions that is compatible with efficient implementation in clinical research environments. Study design: A sensitive, reliable, internally-controlled real-time reverse transcriptase (RT) PCR assay, which uses the HIV-1 pol gene as a target (Hpol assay) was developed to quantify HIV levels in plasma and genital secretions, and compared to the widely used Roche Amplicor(TM) HIV-1 Monitor assay. In addition, a simplified method of sample collection and processing...
Purpose: We present an update analysis of the multiinstitutional Ewing's sarcoma study CESS 86. Methods and Materials: From January 1986 through June 1991, 177 patients with localized Ewing's sarcoma of bone, aged 25 years or less, were recruited. Chemotherapy consisted of four 9-week courses of vincristine, actinomycin D, cyclophosphamide, and adriamycin (VACA) in low-risk tumors (extremity tumors =# 100 cm"3). Local therapy was an individual decision in each patient and was either radical surgery (amputation, wide resection) or resection plus postoperative irradiation with 45 Gy or definitive radiotherapy with 60 Gy (45 Gy plus boost). Irradiated patients were randomized concerning the type of fractionation in either conventional fractionation (once daily 1.8-2.0 Gy, break of chemotherapy) or hyperfractionated split-course irradiation simultaneously with the VACA/VAIA chemotherapy (twice daily 1.6 Gy, break of 12 days after 22.4 Gy and 44.8 Gy, total dose and ...
In this work, we query the Chlamydomonas reinhardtii copper regulon at a whole-genome level. Our RNA-Seq data simulation and analysis pipeline validated a 2-fold cutoff and 10 RPKM (reads per kilobase of mappable length per million mapped reads) (~1 mRNA per cell) to reveal 63 CRR1 targets plus another 86 copper-responsive genes. Proteomic and immunoblot analyses captured 25% of the corresponding proteins, whose abundance was also dependent on copper nutrition, validating transcriptional regulation as a major control mechanism for copper signaling in Chlamydomonas. The impact of copper deficiency on the expression of several O2-dependent enzymes included steps in lipid modification pathways. Quantitative lipid profiles indicated increased polyunsaturation of fatty acids on thylakoid membrane digalactosyldiglycerides, indicating a global impact of copper deficiency on the photosynthetic apparatus. Discovery of a putative plastid copper chaperone ...
Abstract MicroRNAs (miRNAs) play important roles in global gene regulation. Researchers in recombinant protein production have proposed miRNAs as biomarkers and cell engineering targets. However, miRNA expression remains understudied in Chinese Hamster Ovary cells, one of the most commonly used host cell systems for therapeutic protein production. To profile highly conserved miRNA expression, we used the miRCURY- miRNA array for screening miRNAs in CHO cells. The selection criteria for further miRNA profiling included positive hybridization signals and experimentally validated predicted regulatory targets. On the basis of screening, we selected 16 miRNAs for quantitative RT-PCR profiling. We profiled miR expression in parental CHO DG44 and CHO K1 cell lines as well as four recombinant DG44...
Background and purpose: the recent RTOG guidelines for future clinical developments in gynecologic malignancies included the investigation of dose escalation in the paraaortic (PO) region which is, however, very difficult to target due to the presence of critical organs such as kidneys, liver, spinal cord, and digestive structures. The aim of this study was to investigate intensity-modulated radiotherapy's (IMRT) possibilities of either increasing, in a safe way, the dose to 50-60 Gy in case of macroscopic disease or decreasing the dose to organs at risk (OR) when treatment is given in an adjuvant setting. Material and methods: the dosimetric charts of 14 patients irradiated to the PO region at the department of radiation oncology, university hospital of Liege, Belgium, in 2000 were analyzed in order to compare six-field conformal external-beam radio-therapy (CEBR) and five-beam IMRT approaches. Both CEBR and IMRT investigations were ...
Synthetic gene networks can be used to control gene expression and cellular phenotypes in a variety of applications. In many instances, however, such networks can behave unreliably due to gene expression...Full Text Available
Background: Determinants of warfarin use and anticoagulation levels in atrial fibrillation (AF) patients have not been clarified thoroughly. Methods and Results: A total of 6,324 patients with non-valvular AF and congestive heart failure, hypertension, age, diabetes, prior stroke (CHADS(2)) score ?1 were used to investigate determinants of warfarin use, and 6,932 patients with AF receiving warfarin were used to investigate determinants of international normalized ratio (INR) of prothrombin time. Target INR levels for non-valvular AF patients were 1.6-2.6 for patients aged ?70 years and 2-3 for patients aged transient ischemic attack (TIA), and had higher CHADS(2) scores than those not receiving warfarin. Determinants of warfarin use were age (?60 years), AF type (persistent and permanent), and comorbidities (congestive heart failure, diabetes mellitus, and prior stroke or TIA). Use of antiplatelet drugs was a negative determinant of warfarin use. Only 53% of ...
Basal cell carcinoma (BCC) is the most frequent cutaneous neoplasm, with a generally favorable clinical behavior. Sometimes, indeed, it recurs after therapy and/or metastasizes. As point mutations in the coding sequence of the p53 tumor suppressor gene have been implicated in the progression of many human tumors, we studied the expression of p53 protein on this neoplasia. We tested immunohistochemically the positivity for p53 protein (NCL-p53-CM1, YLEM) on 19 cases of morphologically "non aggressive" BCC (BCC1) and on 19 "aggressive" BCC (BCC2), all with one or more relapses and 3 with distant metastases also. Results were related to clinico-pathological and follow-up data. All but one BCC2 were found positive for p53 protein. Conversely, only 2 cases of BCC1 exhibited low immunoreactivity for p53 protein, with high statistical differences between the two groups. No correlation was found between the immunoreactivity, age of patients, and site ...
The retinal degeneration 10 (rd10) mouse is a well-characterized model of autosomal recessive retinitis pigmentosa (RP), which carries a spontaneous mutation in the ? subunit of rod cGMP-phosphodiesterase (PDE?). Rd10 mouse exhibits photoreceptor dysfunction and rapid rod photoreceptor degeneration followed by cone degeneration and remodeling of the inner retina. Here, we evaluate whether gene replacement using the fast-acting tyrosine-capsid mutant AAV8 (Y733F) can provide long-term therapy in this model. AAV8 (Y733F)-smCBA-PDE? was subretinally delivered to postnatal day 14 (P14) rd10 mice in one eye only. Six months after injection, spectral domain optical coherence tomography (SD-OCT), electroretinogram (ERG), optomotor behavior tests, and immunohistochemistry showed tha...
The subjects covered in this Symposium range through almost every clinical medical specialty. From an average of one paper in each of the past three Symposiums, the explosive interest in cerebral amyloidosis has led to the presentation of 12 papers on this subject in the present volume. The genetically predisposed familial amyloidotic processes, such as the polyneuropathies and familial Mediterranean fever have also stimulated extensive and intriguing investigations which have revealed the striking effect of a single amino acid substitution in transforming a normal protein into a lethal ''amyloidogenic'' one. This Symposium clearly depicts the advances since the first amyloid fibril protein was definitively identified and defined 14 years ago. Since all amyloid fibril proteins so far described are variants of normal proteins, attention to gene abnormalities now becomes a significant focus as well as the pathogenic sequences which lead in these cases to twisted ...
A new area-wide pest control strategy using the pink bollworm, Pectinophora gossypiella (Saunders) (Lepidoptera: Gelechiidae), genetically transformed with a conditionally lethal gene, is under development. Conditional lethality of several transgenic pink bollworm strains was demonstrated in a series of laboratory rearing experiments. Pink bollworms were transformed with genetic constructs using the RIDL technology (Release of Insects with a Dominant Lethal gene) for development of an autocidal biological control system for possible supplement or replacement of radiation based sterile insect release. LA1124 is a lethal construct controlled by a tetracycline repressible transactivator protein (tTA), in which binding of tTA to its specific target sequence tetO drives production of more tTA. In the absence of tetracycline, this leads to lethality by high expression of tTA. When tetracycline is present, tTA does not bind tetO, ...
The incidence of hilar cholangiocarcinoma is very rare worldwide. Radical resection is the only prognostic factor for long survival in patients with hilar cholangiocarcinoma. Postoperative radiation therapy can improve local control and survival rates for patients with palliative resection, but it remains controversial in patients with radical resection. Biliary drainage can effectively release bile duct obstruction for the majority of patients with locally advanced disease, and may even prolong survival when combined with radiation therapy. Radiation therapy includes extrernal beam therapy alone, external beam therapy with intraluminal brachytheapy and new radiation technique, such as three dimentional conformal therapy and intensity modulated radiation therapy. The propective randomized clinical study is needed for further investigation in ...
Therapeutic hypothermia is a promising method for controlling intracranial pressure (ICP) in severely brain-injured patients. However, clinical data regarding the effect of brain hypothermia on overall outcome of these patients is limited. This may be because there are specific pitfalls associated with the clinical management of induced hypothermia in patients with severe traumatic brain injury (TBI). These pitfalls may be avoided by preventing specific risk factors when cooling is induced and with rewarming. However, these risk factors have not been well systematically discussed in the literature. In this paper, three categories of clinical issues regarding the management of brain hypothermia are discussed: (1) stress-induced secondary brain injury mechanisms; (2) technical aspects of intensive care unit (ICU) cooling management; and (3) rewarming rates and methods. For patients with a Glasgow Coma Scale (GCS) score of less than 8, management of stress-induced insulin-resistant ...
A method has been developed for calibration of CT-numbers to volumetric electron density distributions using tissue substitutes of known elemental composition and experimentally determined electron density. This information have been used in a dose calculation method based on photon and electron interaction processes. The method utilizes a convolution integral between the photon fluence matrix and dose distribution kernels. Inhomogeneous media are accounted for using the theorems of Fano and O'Connor for scaling dose distribution kernels in proportion to electron density. For clinical application of a calculated dose plan, a method for prediction of accelerator output have been developed. The methods gives the number of monitor units that has to be given to obtain a certain absorbed dose to a point inside an irregular, inhomogeneous object. The method for verification of dose distributions outlined in this study makes it possible to exclude the treatment related variance contributions, ...
Current antidotal regimens for organophosphorus compound (OP) poisoning consist of a combination of pretreatment with a spontaneously reactivating AChE inhibitor such as pyridostigmine bromide, and postexposure therapy with anticholinergic drugs such as atropine sulfate and oximes such as 2-PAM chloride (Gray, 1984). Although these antidotal regimens are effective in preventing lethality of animals from OP poisoning, they do not prevent postexposure incapacitation, convulsions, performance deficits, or, in many cases, permanent brain damage (Dunn and Sidell, 1989). These problems stimulated the development of enzyme bioscavengers as a pretreatment to sequester highly toxic OPs before they reach their physiological targets. Several studies over the last two decades have demonstrated that exogenously administered human serum butyrylcholinesterase (Hu BChE) can be used successfully as a safe, efficacious, and single prophylactic treatment to ...
Beams may be viewed as directed and focussed flow of energy and information, carried by particles and electromagnetic radiation fields (ie, photons). Often, they interact with each other (eg, in high energy colliders) or with other forms of matter (eg, in fixed targets, sychrotron radiation, neutron scattering, laser chemistry/physics, medical therapy, etc.). The whole art and science of beams revolve around the fundamental quest for, and ultimate implementation of, mechanisms of production, storage, control and observation of beams -- always directed towards studies of the basic structures and processes of the natural world and various practical applications. Tremendous progress has been made in all aspects of beam physics and technology in the last decades -- nonlinear dynamics, superconducting magnets and rf cavities, beam instrumentation and control, novel concepts and collider praradigms, to name a few. We illustrate this progress with a ...
What genes are related to AEC syndrome? AEC syndrome is caused by mutations in the TP63 gene. This gene provides instructions for making a protein known as p63, which plays an...
Purpose: Photodynamic therapy (PDT) is based on the interaction of a photosensitizing (PS) agent, light, and oxygen. Few new PS agents are being developed to the in vivo stage, partly because of the difficulty in finding the right treatment conditions. Response surface methodology, an empirical modeling approach based on data resulting from a set of designed experiments, was suggested as a rational solution with which to select in vivo PDT conditions by using a new peptide-conjugated PS targeting agent, neuropilin-1. Methods and Materials: A Doehlert experimental design was selected to model effects and interactions of the PS dose, fluence, and fluence rate on the growth of U87 human malignant glioma cell xenografts in nude mice, using a fixed drug-light interval. All experimental results were computed by Nemrod-W software and Matlab. Results: Intrinsic diameter growth rate, a tumor growth parameter independent of the initial volume of the ...
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and has very limited therapeutic options. Recently, it has been found that hyaluronic acid (HA) shows selective binding to CD44 receptors expressed in most cancer histotypes. Since the trend in cancer treatment is the use of targeted radionuclide therapy, the aim of this research was to label HA with rhenium-188 and to evaluate its potential use as a hepatocarcinoma therapeutic radiopharmaceutical. Methods: {sup 188}Re-HA was prepared by a direct labelling method to produce a ReO(O-COO){sub 2}-type coordination complex. {sup 188}Re-HA protein binding and its stability in saline, phosphate buffer, human serum and cysteine solutions were determined. Biokinetic and dosimetric data were estimated in healthy mice (n=60) using the Medical Internal Radiation Dose methodology and mouse model beta-absorbed fractions. To evaluate liver toxicity, alanine aminotranferase (AST) and ...
BackgroundTransarterial chemoembolization (TACE) therapy is an effective locoregional treatment in hepatocellular cancer (HCC) patients. For early modification of therapy, markers...Full Text Available
Forty-four patients with histologically proven Hodgkin's disease underwent initial treatment with extended-field radiation therapy. Nineteen of these patients also received combination chemotherapy....Full Text Available
The importance of intact host defense mechanisms for successful antimicrobial therapy was investigated in an animal model. Recovery from lobar pneumococcal pneumonia as a result of penicillin therapy...Full Text Available
Radionuclide bone metastases therapy is a major achievement of nuclear medicine. Development of less radiotoxic and more effective radiopharmaceuticals is therefore a challenge for radiopharmacists and industry. This paper reviews the application of rhenium-188 HEDP as a reactor- or generator-produced nuclide for bone metastases therapy. (author)
The rice blast resistance (R) gene Pi-ta mediates gene-for-gene resistance against strains of the fungus Magnaporthe grisea that express avirulent...Full Text Available
BackgroundInferring regulatory interactions between genes from transcriptomics time-resolved data, yielding reverse engineered gene regulatory networks, is of paramount importance...Full Text Available
The "ovalbumin Y" gene, one of three which constitute the ovalbumin gene family in chicken has been completely sequenced. The exact location of exons can be derived from the comparison with the ovalbumin...Full Text Available
BackgroundGene duplication is the primary force of new gene evolution. Deciphering whether a pair of duplicated genes has evolved divergent functions is often challenging. The zebrafish...Full Text Available
BackgroundMicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression by binding to the messenger RNA (mRNA) of protein coding genes. They control gene expression by either...Full Text Available
The functional gene and three intronless pseudogenes for human triosephosphate isomerase were isolated from a recombinant DNA library and characterized in detail. The functional gene spans 3.5 kilobase...Full Text Available
Molecular analysis of the amo gene cluster in Nitrosococcus oceani revealed that it consists of five genes, instead of the three known genes, amoCAB....Full Text Available
We develop a statistical framework to study the relationship between chromatin features and gene expression. This can be used to predict gene expression of protein coding genes, as well as microRNAs....Full Text Available
We proposed a faster pedigree-based generalized multifactor dimensionality reduction algorithm, called PedG-MDR II (PII), to detect gene-gene interactions underlying complex traits. Inherited...Full Text Available
The current therapy for extrinsic and intrinsic asthma, together with that of ‘wheezing bronchitis’, is presented, with special attention to bronchodilators and adrenocorticosteroids....Full Text Available
PurposeTo determine the dosimetric impact of inter-fraction anatomical movements in prostate cancer patients receiving proton therapy.Full Text Available
1 Recommendations for correct therapy with digoxin from twenty-five sources are reviewed. 2 Some recommendations may be unsuitable for use with high bioavailability...Full Text Available
... radiation during clinical therapy and exposures due to radiation accidents or attacks, in which the doses are uncontrolled ... only be used off-label in victims of radiation accidents or attacks. The idea...
Boron Neutron Capture Therapy (BNCT) is a promising binary treatment modality for high-grade primary brain tumors (glioblastoma multiforme, GM) and other cancers. BNCT employs a boron-10 containing compound that preferentially accumulates in the cancer cells in the brain. Upon neutron capture by {sup 10}B energetic alpha particles and triton released at the absorption site kill the cancer cell. In order to gain penetration depth in the brain Fairchild proposed, for this purpose, the use of energetic epithermal neutrons at about 10 keV. Phase I/II clinical trials of BNCT for GM are underway at the Brookhaven Medical Research Reactor (BMRR) and at the MIT Reactor, using these nuclear reactors as the source for epithermal neutrons. In light of the limitations of new reactor installations, e.g. cost, safety and licensing, and limited capability for modulating the reactor based neutron beam energy spectra alternative neutron sources are being contemplated for wider ...
Full text: Radiotherapy treatment planning (RTP) relies heavily on medical imaging. Until recently, the most important planning tool was the treatment simulator. The kilovoltage radiographic capabilities in a treatment simulator enabled the boundaries of treatment fields to be visualized with respect to bony anatomic landmarks. Perhaps the most important advance in treatment planning in recent years is the ability to visualize the passage of the beams with respect to a more accurate geometrical representation of the tumor and other soft tissue structures. This 'virtual simulation' uses a computer-based representation of a patient to determine the extent of the disease and the location of radiation sensitive normal tissue. Computer tomographic (CT) imaging produces a high-resolution three-dimensional representation of anatomy that can be correlated with other image sets such as magnetic resonance images (MRI) of function. Positron emission tomographic (PET) imaging is beginning to be ...
The structural organization of the genes encoding Bungarus multicinctus protease inhibitor-like proteins (PILPs), PILP-1, PILP-2 and PILP-3, are reported in this study. Unlike PILP-2 and PILP-3, recombinant PILP-1 exhibited inhibitory activity on trypsin. PILP genes and B chain genes shared identical organization with three exons interrupted by two introns in similar positions. On the contrary, intron 1 of these genes had a similar size, a notable variation with the size of intron 2 was observed. It was found that two regions at the second intron of B1 chain and B2 chain genes were absent in that of PILP genes. Noticeably, intronic insertion in the second intron of B chain genes appeared in the promoter region of PILP-1 gene, but not in that of PILP-2 and PILP-3 genes. Comparative analyses of PILP ...
We have constructed a 27-kDa hTERT C-terminal polypeptide (hTERTC27) devoid of domains required for telomerase activity and demonstrated that it is capable of nuclear translocation/telomere-end targeting. Here we showed that expression of a low level of hTERTC27 renders hTERT positive HeLa cells sensitive to H(2)O(2)-induced oxidative stress and subsequent cell senescence. The senescence-associated gene, the cyclin/cdk inhibitor p21(Waf1), was up-regulated. This occurs without changing the expression of endogenous hTERT, causing significant telomere shortening or inhibiting telomerase activity. Results from this study suggest for the first time that in addition to telomerase activity, the C-terminus of hTERT also plays a role in hTERT-mediated cellular resistance to oxidative stress. PMID:12565825
Radiation therapy has shown definite technical improvement due to application of proton beam irradiation. Clinical results of proton beam therapy also suggested enlargement of indication ranges in radial treatment and decrease of post radiation damages of the treatment of cancers in deep-seated organs. Inprovement of result in cancer therapy could be expected by this treatment technique in the future.
BackgroundTo compare two strategies of dynamic intensity modulated radiation therapy (dIMRT) with 3-dimensional conformal radiation therapy (3DCRT) in the setting of hypofractionated...Full Text Available
Radiotherapy can be very significant as the treatment for ocular lesions, eyes need to be preserved as properly as possible on their functions and cosmetics. The application of conventional X ray therapy has been gradually abandoned as conventional X ray therapy ceased to be accepted as the general treatment for malignant tumors. Consequently the necessity of electron beam therapy has been rising even as the substituted method for conventional X ray therapy. The department of radiology of Gunma University was obliged to establish a new therapy for ocular lesions, and has been trying electron beam therapy since 1973. It is concluded that electron beam therapy is not at all inferior to conventional X ray therapy as reported above. Basic therapeutic methods for ocular lesions are the following: 1) For epidermoid carcinoma, ...
The detection of foot-and-mouth disease (FMD) virus from various kinds of field samples (tissue extract and cell culture isolate) was studied using the polymerase chain reaction (PCR) technique. The gene selected for diagnosis was the polymerase gene and an amplification target product of 454 bp in length was produced using AP5/AP6 primer sets. The PCR product was further examined by NcoI endonuclease digestion. The presence of the internal restriction site was confirmed by demonstration of two small fragments of 330 bp and 124 bp in length. Forty-nine samples that gave positive and negative results by ELISA typing and were positive by the PCR test were tested by NcoI digestion to confirm the results. About 10% of PCR products could not be confirmed by the method. Furthermore the FMD RNA polymerase gene could be detected by the PCR method in samples negative in both ELISA typing and the virus isolation ...
This paper reported on a study in which designs for Chinese and Indian fixed-dome anaerobic digesters were modified in an effort to produce smaller and more affordable digesters. While these types of systems are common in tropical regions of developing countries, they have not been used in colder climates because of the low biogas yield during the winter months. Although there is evidence that sufficient biogas production can be maintained in colder temperatures through design and operational changes, there is a lack of knowledge about the seasonal changes in the composition of the microbial communities in ambient temperature digesters. More knowledge is needed to design and operate systems for maximum biogas yield in temperate climates. The purpose of this study was to cultivate a microbial community that maximizes biogas production at psychrophilic temperatures. The study was conducted on a 300 gallon experimental anaerobic digester on the campus of Ohio State University. ...
The accuracy of dose computation within the lungs depends strongly on the performance of the calculation algorithm in regions of electronic disequilibrium that arise near tissue inhomogeneities with large density variations. There is a lack of data evaluating the performance of highly developed analytical dose calculation algorithms compared to Monte Carlo computations in a clinical setting. We compared full Monte Carlo calculations (performed by our Monte Carlo dose engine MCDE) with two different commercial convolution/superposition (CS) implementations (Pinnacle-CS and Helax-TMS's collapsed cone model Helax-CC) and one pencil beam algorithm (Helax-TMS's pencil beam model Helax-PB) for 10 intensity modulated radiation therapy (IMRT) lung cancer patients. Treatment plans were created for two photon beam qualities (6 and 18 MV). For each dose calculation algorithm, patient, and beam quality, the following set of clinically relevant dose-volume values was reported: ...
Isolation and expansion of neural stem cells (NSCs) of human origin are crucial for successful development of cell therapy approaches in neurodegenerative diseases. Different epigenetic and genetic immortalization strategies have been established for long-term maintenance and expansion of these cells in vitro. Here we report the generation of a new, clonal NSC (hc-NSC) line, derived from human fetal cortical tissue, based on v-myc immortalization. Using immunocytochemistry, we show that these cells retain the characteristics of NSCs after more than 50 passages. Under proliferation conditions, when supplemented with epidermal and basic fibroblast growth factors, the hc-NSCs expressed neural stem/progenitor cell markers like nestin, vimentin and Sox2. When growth factors were withdrawn, proliferation and expression of v-myc and telomerase were dramatically reduced, and the hc-NSCs differentiated into glia and neurons (mostly glutamatergic and GABAergic, as well as ...
Transposons are promising systems for somatic gene integration because they can not only integrate exogenous genes efficiently, but also be delivered to a variety of organs using a range of transfection...Full Text Available
The genome sequence of the Mamavirus, a new Acanthamoeba polyphaga mimivirus strain, is reported. With 1,191,693 nt in length and 1,023 predicted protein-coding genes, the Mamavirus...Full Text Available
BackgroundVariation of gene number among species indicates that there is a general process of new gene origination. One of the major mechanism providing raw materials for the origin...Full Text Available
The gram-positive pathogen Streptococcus pyogenes was recently reported to possess a homologue of the luxS gene that is responsible for the production of autoinducer...Full Text Available
Activation-induced deaminase (AID) initiates somatic hypermutation, gene conversion and class switch recombination by deaminating variable and switch region DNA cytidines to uridines. AID is predominantly...Full Text Available
Previous studies have been conducted in gene expression profiling to identify groups of genes that characterize the colorectal carcinoma disease. Despite the success of previous attempts to identify...Full Text Available
Reverse engineering of gene regulatory networks has been an intensively studied topic in bioinformatics since it constitutes an intermediate step from explorative to causative gene expression...Full Text Available
Variant alleles of the mannose binding lectin (MBL) gene are associated with increased susceptibility to infection and polymorphisms of tumour necrosis factor and lymphotoxin alpha genes (TNF, LTA)...Full Text Available
We have examined the expression and structure of several genes belonging to two classes of vegetative specific genes of the simple eukaryote, Dictyostelium discoideum. In amebae grown on bacteria, deactivation...Full Text Available
BackgroundDifferent microarray studies have compiled gene lists for predicting outcomes of a range of treatments and diseases. These have produced gene lists that have little overlap,...Full Text Available
OBJECTIVE—Identification of arterial genes and pathways altered in obesity and diabetes.RESEARCH DESIGN AND METHODS—Aortic gene expression profiles of...Full Text Available
A plasmid carrying the bacteriophage lambda lysis genes under lac control was subjected to hydroxylamine mutagenesis, and mutations eliminating the host lethality of the S gene were selected. DNA sequence...Full Text Available
BackgroundMicroarray data are often used for patient classification and gene selection. An appropriate tool for end users and biomedical researchers should combine user friendliness...Full Text Available
Despite the recent success of genome-wide association studies (GWASs) in identifying loci consistently associated with coronary artery disease (CAD), a large proportion of the genetic components of...Full Text Available
Most human diseases are related in some way to the loss or gain in gene functions. Regulation of gene expression is a complex process. In addition to genetic mechanisms, epigenetic causes are...Full Text Available
The Japanese medaka fish Oryzias latipes has an XX/XY sex-determination system. The Y-linked sex-determination gene DMY is a duplicate of the autosomal gene DMRT1, which encodes a DM-domain-containing...Full Text Available
BackgroundCells dynamically adapt their gene expression patterns in response to various stimuli. This response is orchestrated into a number of gene expression modules consisting...Full Text Available
We have isolated a second gene (MLS1), which in addition to DAL7, encodes malate synthase from S. cerevisiae. Expression of the two genes is specific for their physiological roles in carbon and nitrogen...Full Text Available
The protein kinase CK2 (formerly casein kinase II) is thought to be involved in light-regulated gene expression in plants because...Full Text Available
BmpA, BmpB, BmpC, and BmpD are homologous Borrelia burgdorferi lipoproteins of unknown functions, encoded by the bmp genes of paralogous chromosomal gene family 36....Full Text Available
In filamentous fungi, RNA silencing is an attractive alternative to disruption experiments for the functional analysis of genes. We adapted the gene encoding the autofluorescent DsRed protein as a reporter...Full Text Available
With the advent of intensity-modulated radiation therapy (IMRT), the inclusion of heterogeneity corrections is further complicated by the conformal delivery of many small beams forming steep dose gradients. Radiation treatment planning has evolved to take into account even small changes in tissue density so that the dose to tumor can be further optimized. However, different treatment planning systems incorporate different heterogeneity correction algorithms, and it is unclear whether any of these algorithms are superior to others in terms of accurately predicting delivered radiation doses relative to measurement in a clinical setting. The purpose of this study was to determine the accuracy of heterogeneity dose calculations from two widely used IMRT treatment planning systems (Pinnacle and Corvus) against measurement. These two systems handle heterogeneity dose corrections by means of a collapsed-cone convolution superposition algorithm and a finite-size ...
We report the identification and characterization of a new Drosophila clock-regulated gene, takeout (to). to is a member of a novel...Full Text Available
Recessive mutations of the early phase change (epc) gene in maize affect several aspects of plant development. These mutations were identified initially because of...Full Text Available
Gene expression is a fundamentally stochastic process, with randomness in transcription and translation leading to significant cell-to-cell variations in mRNA and protein levels. This variation...Full Text Available
The ras oncogenes function by indirectly controlling expression of a subset of yet-undefined genes that are crucial for cell growth and differentiation. In a differential display strategy, numerous...Full Text Available
These proceedings collect papers on the subject of lymphokines. Topics include: DNA-cloning of mouse and human lymphokine genes, inteferons, interleukins, gene expression, tumor necrosis factors, and recombinant DNA.
PASTICCINO (PAS) genes are required for coordinated cell division and differentiation during plant development. In loss-of-function pas mutants,...Full Text Available
Mutations in the Drosophila gene drop-dead (drd) result in early adult lethality and neurodegeneration, but the molecular identity of the drd...Full Text Available
Cis-acting regulatory sequences are required for the proper temporal and spatial control of gene expression. Variation in gene expression is highly heritable and a significant determinant...Full Text Available
For a given linac design, the dosimetric characteristics of a photon beam are determined uniquely by the energy and radial distributions of the electron beam striking the x-ray target. However, in the usual commissioning of a beam from measured data, a large number of variables can be independently tuned, making it difficult to derive a unique and self-consistent beam model. For example, the measured dosimetric penumbra in water may be attributed in various proportions to the lateral secondary electron range, the focal spot size and the transmission through the tips of a non-divergent collimator; the head-scatter component in the tails of the transverse profiles may not be easy to resolve from phantom scatter and head leakage; and the head-scatter tails corresponding to a certain extra-focal source model may not agree self-consistently with in-air output factors measured on the central axis. To reduce the number of adjustable variables in beam modelling, we replace ...
To assess the efficacy and resulting complications of tetracycline sclerotherapy in renal, hepatic, ovarian, and perivesical cysts. We retrospectively reviewed 23 cases of benign cysts (16 renal, 4 hepatic, 2 ovarian, and 1 perivesical) in 22 patients in whom the condition was diagnosed or confirmed by either ultrasound, CT, or cytology, and who underwent percutaneous tetracycline sclerotherapy. Using a 21-gauge Chiba needle, the target cyst was punctured under ultrasound guidance. Prior to the injection of 1500 mg of tetracycline diluted in 5 ml of normal saline, almost all the cystic content was aspirated, and at the end of the procedure the tetracycline was left in the cyst. During a period of between 3 and 22 months, 18 of the 23 cases were followed up. In six of the 18 cases followed up, the cysts either decreased in size by 10%, or collapsed completely. In seven cases a collapse of over 50% was noted, and in the remaining five the cyst recurred. In one of ...
Stereotactic radiosurgery (SRS) precisely delivers high-dose radiation to a small target (usually less than 3-4 cm in diameter), in a single session with steep dose-fall, employing various radiation methods. SRS provides good tumor control for small brain metastases from various primary cancers, with minimal untoward effects on surrounding normal brain. This excellent tumor control prevents neurological death and maintains good activity of daily life. Although surgery with whole-brain radiation therapy (WBRT) remains an important option for patients with a solitary brain metastasis, SRS with or without WBRT should be considered in patients with a limited number of small tumors and a good prognosis. Many reports, as well as both retrospective and prospective reviews, have shown WBRT before or after SRS to improve local control and reduce new distant lesion emergence. However, upfront WBRT does not improve survival. There are two major delivery ...
This study examined whether cognitive behavioural therapy (CBT) could prevent the development or worsening of panic-spectrum psychopathology and anxiety symptoms in chronic obstructive pulmonary disease (COPD). 41 patients with COPD, who had undergone pulmonary rehabilitation, were randomised to either a four-session CBT intervention condition (n = 21) or a routine care condition (n = 20). Assessments were at baseline, post-intervention, and at 6-, 12- and 18-month follow-ups. Primary outcomes were the rates of panic attacks, panic disorder and anxiety symptoms. Secondary outcomes were depressive symptoms, catastrophic cognitions about breathing difficulties, disease-specific quality of life and hospital admission rates. There were no significant differences between the groups on outcome measures at baseline. By the 18-month follow-up assessment, 12 (60%) routine care group participants had experienced at least one panic attack in the previous 6 months, with two ...
Humoral immune response to human epidermal growth factor receptor 2 (HER-2/neu or ErbB-2) has been detected in sera of breast cancer patients and shown to be an appropriate prognostic marker (Taylor et al., 2007). However, since Trastuzumab (Herceptin) is a widely used monoclonal antibody as cancer therapy agent for tumors over-expressing HER-2, there is a need for an efficient way to detect host-generated antibodies against HER-2 without the confounding effect of Herceptin. Here we describe a screening method developed to decipher between host antibodies against HER-2 and that of Herceptin. By producing a series of truncation mutants within the epitope of Herceptin, we were able to inhibit this binding. We demonstrated also that by a three amino acid substitution (PPF?SSS) we were able to abrogate Herceptin binding while generating a highly conserved HER-2 extracellular domain (ECD). By producing a stable cell line that expresses this mutated form of the human ...
The Anisotropic Analytical Algorithm (AAA) is a new pencil beam convolution/superposition algorithm proposed by Varian for photon dose calculations. The configuration of AAA depends on linear accelerator design and specifications. The purpose of this study was to investigate the accuracy of AAA for an Elekta SL25 linear accelerator for small fields and intensity modulated radiation therapy (IMRT) treatments in inhomogeneous media. The accuracy of AAA was evaluated in two studies. First, AAA was compared both with Monte Carlo (MC) and the measurements in an inhomogeneous phantom simulating lung equivalent tissues and bone ribs. The algorithm was tested under lateral electronic disequilibrium conditions, using small fields (2x2 cm"2). Good agreement was generally achieved for depth dose and profiles, with deviations generally below 3% in lung inhomogeneities and below 5% at interfaces. However, the effects of attenuation and scattering close to the bone ribs were not ...
The implementation of a three-dimensional conformal radiotherapy facility in the radiotherapy department of the Heinrich Heine University is described. Complex radiotherapy techniques with commercially available networked systems are introduced to improve clinical work. Over 18 month we have gained clinical experience with a PHILIPS Multileaf Collimator (MLC) mounted on a SL 25 linear accelerator. For a limited period the MLC was used as a conventional blocking device. The standard MLC-shapes are controlled with a stand-alone computer system. In addition, a three-dimensional treatment planning system (3-D-TPS / TMS-Radix, Helax AB) based on convolution/superposition algorithms was recently installed. Treatment optimization is achieved using static field arrangements with complete volumetric computerized tomographic patient data for 3-D-TPS. Conformal adaptation of the 95%-isodose to the Planning Target Volume (PTV, ICRU 50) results in MLC-field-shaping concerning ...
A new leaf-sequencing approach has been developed that is designed to reduce the number of required beam segments for step-and-shoot intensity modulated radiation therapy (IMRT). This approach to leaf sequencing is called continuous-intensity-map-optimization (CIMO). Using a simulated annealing algorithm, CIMO seeks to minimize differences between the optimized and sequenced intensity maps. Two distinguishing features of the CIMO algorithm are (1) CIMO does not require that each optimized intensity map be clustered into discrete levels and (2) CIMO is not rule-based but rather simultaneously optimizes both the aperture shapes and weights. To test the CIMO algorithm, ten IMRT patient cases were selected (four head-and-neck, two pancreas, two prostate, one brain, and one pelvis). For each case, the optimized intensity maps were extracted from the Pinnacle"3 treatment planning system. The CIMO algorithm was applied, and the optimized aperture shapes and weights were ...
Experimental excitation functions for deuteron-induced reactions up to 20 MeV on high purity natural hafnium were measured with the activation method using a stacked foil irradiation technique. Metallic hafnium foils with thickness of 10 #mu#m were stacked together with 50 #mu#m thick aluminium and 12 #mu#m thick titanium foils. The aluminium foils served as energy absorber while the titanium foils were used to monitor the energy and intensity of the bombarding deuteron beam. From a detailed remeasurement of the complete excitation function of the "n"a"tTi(d,x)"4"8V monitor reaction it was possible to adopt the proper incident energy and beam intensity by comparing the results with the recommended values. High resolution off-line gamma-ray spectrometry was applied to assess the activity of each foil. From the measured activity independent and/or cumulative elemental or isotopic cross section data for production of Ta, Hf and Lu radioisotopes by (d,x) reactions were determined. No ...
The side effects of cancer therapy on normal tissues limit the success of therapy. Generation of reactive oxygen species (ROS) has been implicated for numerous chemotherapeutic agents including doxorubicin...Full Text Available
BackgroundIt remains unclear if certain antiretroviral medications, particularly abacavir, compromise response to hepatitis C virus (HCV) therapy. Such data can inform...Full Text Available
BackgroundAdolescents have been identified as a high-risk group for poor adherence to and defaulting from combination antiretroviral therapy (cART) care. However, data on outcomes...Full Text Available
A simple device is described which is used to determine treatment distance and beam direction in electron therapy employing one collimation. A technique for the production of irregular field templates and localization films is given.
ObjectivesTo investigate the effect of group cognitive behavioural therapy (CBT) for fatigue self-management, compared with groups receiving fatigue information alone, on fatigue...Full Text Available
BackgroundTo assess the relationship between improved regional and global myocardial function in patients with ischemic cardiomyopathy in response to β-blocker therapy or...Full Text Available
Current adherence assessments typically detect missed doses long after they occur. Real-time, wireless monitoring strategies for antiretroviral therapy may provide novel opportunities to proactively...Full Text Available
BackgroundThe aim of this study was to compare and to validate different dose calculation algorithms for the use in radiation therapy of small lung lesions and to optimize the treatment...Full Text Available
BackgroundThe lack of adequate randomized clinical trials (RCT) has hindered identification of new therapies that are safe and effective for patients with primary focal segmental...Full Text Available
Adaptive radiation therapy (ART) is the incorporation of daily images in the radiotherapy treatment process so that the treatment plan can be evaluated and modified to maximize the amount of radiation...Full Text Available
Photodynamic therapy (PDT) is an established endoscopic technique for ablating Barrett’s esophagus with high-grade dysplasia or early-stage intraepithelial neoplasia. The most common clinically...Full Text Available
BackgroundArtemisinin-based combination therapy, currently considered the therapy of choice for uncomplicated Plasmodium falciparum malaria in endemic countries,...Full Text Available
Several compact proton accelerator systems for use in proton therapy have recently been proposed. Of paramount importance to the development of such an accelerator system is the maximum kinetic energy...Full Text Available
The effect of Photofrin-based photodynamic therapy (PDT) and adjuvant treatment with serum vitamin D3-binding protein-derived macrophage-activating factor (DBPMAF) was examined using a mouse SCCVII...Full Text Available
BackgroundHerpes simplex virus (HSV) suppressive therapy reduces genital and plasma HIV-1 RNA over periods up to three months but the longer-term effect is unknown.Full Text Available
Somatic cell nuclear transfer or therapeutic cloning has provided great hope for stem cell-based therapies. However therapeutic cloning has been experiencing both ethical and technical difficulties....Full Text Available
ObjectiveTo evaluate the effect of different concomitant disease modifying antirheumatic drugs (DMARDs) on the persistence with antitumour necrosis factor (anti-TNF) therapies in...Full Text Available
Suppressed IL-12 production and maladaptive immune activation, both of which are ameliorated by successful highly active antiretroviral therapy (HAART), are thought to play important roles in the immunopathogenesis...Full Text Available
Purpose: Understanding the kinetics of tumor growth∕shrinkage represents a critical step in quantitative assessment of therapeutics and realization of adaptive radiation therapy....Full Text Available
Purpose:The risks and benefits of continuing bisphosphonate therapy beyond 5 years in patients with primary osteoporosis have not been well established.Methods:We...Full Text Available
Some studies suggest that giving radiation therapy after surgery for hilar cholangiocarcinoma improves the survival rate; however, many of these studies did not specify numbers of subjects or provide an impartial analysis. Thus, we evaluated the effectiveness of radiation therapy as adjuvant treatment after surgery and attempted to establish appropriate adaptation standards. We reviewed the records of 69 patients who underwent surgery for hilar cholangiocarcinoma between June 1980 and April 1998. Thirty-nine patients were treated with surgery followed by radiation therapy and 30 were treated with surgery alone. The clinicopathologic features that might have influenced prognosis were similar in the patients who received radiation therapy and those who did not. Radiation as adjuvant therapy did not have a beneficial effect on overall survival (P=0.554, log-rank test); however, it ...
Multiple disease-specific systematic reviews on the effectiveness of physical therapy intervention for shoulder dysfunction have been inconclusive. To date, there have been two systematic reviews that...Full Text Available
IntroductionThe optimal dialysis dose for the treatment of acute kidney injury (AKI) is controversial. We sought to evaluate the relationship between renal replacement therapy (RRT)...Full Text Available
... and at that point she had already failed physical therapy, which someone else had prescribed, and so ... MRI, we may try a brief course of physical therapy to see if they feel better, but ...
PurposeA dosimetric comparison between multiple static-field intensity-modulated radiation therapy (IMRT), multi-arc intensity-modulated arc therapy (IMAT) and single-arc...Full Text Available
ObjectiveTo report the efficacy and safety of combined photodynamic therapy (PDT) and intravitreal bevacizumab (IVB) injection in the treatment of idiopathic polypoidal choroidal...Full Text Available
Premature circuit clotting is a major problem in daily practice of continuous renal replacement therapy (CRRT), increasing blood loss, workload, and costs. Early clotting is related to bioincompatibility,...Full Text Available
This study was an evaluation of the performance of self-applied, blue light, light-emitting diode therapy in the treatment of mild-to-moderate inflammatory acne on the face, concerning: 1) time to improvement...Full Text Available
This joint statement was developed by the CMA and the Canadian Pharmaceutical Association, a national association of pharmacists, and includes the goal of drug therapy, strategies for collaboration...Full Text Available
BackgroundPostnatal glucocorticoid therapy in premature infants diminishes chronic lung disease, but it also increases the risk of hypertension in adulthood. Since glucocorticoid...Full Text Available
Adjuvant therapy aims to prevent outgrowth of residual disease but can induce serious side effects. Weighing conflicting treatment effects and communicating this information with patients is not elementary....Full Text Available
In many radiotherapy clinics, geometric uncertainties in the delivery of 3D conformal radiation therapy and intensity modulated radiation therapy of the prostate are reduced by aligning the...Full Text Available
The proton therapy gives an irradiation adapted to the shape and the depth of tumors ( eyes, head and neck) with a millimetric, even sub millimetric precision for the ophthalmological tumors. It is equally an excellent tool for the pediatrics tumors. For numerous treatments in France the proton therapy is associated to the photons treatments (x radiation). however, others physical treatments could modulate the medical offer, such thermal therapy or treatments by ultrasonic waves. (N.C.)
The Monte Carlo transport codes LAHET and MCNP were used to calculate energy fluence spectra at three neutron therapy facilities. The results compare very favourably with measured data. Kerma spectra and the ratio of ICRU muscle tissue kerma to A-150 kerma, along the carbon to oxygen kerma ratio, were determined. Absorbed dose rate calculations are in reasonable agreement with measured values. Use of these codes to study modifications to existing therapy beams is briefly discussed. (author).
The anesthetic agents methohexital (Brevital), Innovar, and ketamine (Ketaject) were examined for their effect on seizure duration following electroconvulsive stimulation in a rat model of electroconvulsive therapy (ECT). Compared to unanesthetized control animals, methohexital anesthesia shortened seizure duration by 42%, ketamine anesthesia tended to increase seizure duration, and Innovar anesthesia had no effect on duration of seizures. PMID:7349626
IntroductionBreast cancer is the most diagnosed and second leading cause of cancer deaths in the U.S. female population. An estimated 5 to 10 percent of all breast cancers are inherited, caused by mutations in the breast cancer susceptibility genes (BRCA1/2). As many as 90% of all mutations are nonsense mutations, causing a truncated polypeptide product. A popular and low cost method of mutation detection has been the protein truncation test (PTT), where target regions of BRCA1/2 are PCR amplified, transcribed/translated in a cell-free protein synthesis system and analyzed for truncated polypeptides by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography. We previously reported a novel High Throughput Solid-Phase PTT (HTS-PTT) based on an enzyme-linked immunosorbent assay (ELISA) format that eliminates the need for radioactivity, SDS-PAGE and subjective interpretation of the results. Here, we report the next ...
With the aim of an experimental check on the validity of the theory of molecular recognition, the authors have carried out the chemical-enzymatic synthesis and cloning of the gene of human calcitonin and also of the genes of antisense polypeptides to human calcitonin and miniproinsulin. It has been shown that recombinant plasmids obtained on the basis of these synthetic genes are capable of ensuring the biosynthesis of the given polypeptides in E. coli cells as hybrid proteins with the IgG-binding domain of staphylococcal protein A.
A 13.1-kb DNA fragment carrying Pseudomonas denitrificans cob genes has been sequenced. The nucleotide sequence and genetic analysis revealed that this fragment contained five different cob genes named...Full Text Available
Procedures are described for the use of synthetic oligonucleotides for Southern blot experiments and gene bank screening, and the effect of various mismatches on the efficiency of hybridization is demonstrated. The following topics are discussed: sensitivity vs. specificity, hybridization of a 12-mer to the lambda endolysin gene; hybridization of oligonucleotide probes to the E. coli lac operator; hybridization of synthetic probes to the CYC1 gene of yeast; and cloning eucaryotic genes. (HLW)
We have isolated the human prointerleukin 1 (proIL-1) beta gene from leukocyte and fetal liver libraries. The nucleotide sequence and its gene organization reveals that the proIL-1 beta gene is composed...Full Text Available
Today you will learn about the parts of DNA and what DNA, genes and chromosomes are. Today you will learn what DNA, genes and chromosomes are and the parts of the DNA molecule. Look at all of the websites, take whatever notes you need to. At the end of the assignment, be able to describle DNA, the parts of DNA, genes and chromosomes. Covers Biology Core Curriculum, ...
The maintenance of a balance between cell gain and cell loss is essential for proper liver function. The exact role of aryl hydrocarbon receptor (AhR) in regulating cell proliferation and apoptosis of liver cells remains unclear, since ligand-dependent activation of AhR has been shown to induce cell cycle arrest, proliferation, differentiation or apoptosis, depending on the cellular model used. AhR can directly interact with retinoblastoma protein in hepatic cells, forming protein complexes that can efficiently block cell cycle progression by inducing G1 arrest, or to induce the expression of inhibitors of cyclin-dependent kinases, such as p271. On the other hand, it has been suggested that AhR could play a stimulatory role in cell proliferation, either directly or by mediating a release from contact inhibition. It is now generally accepted that progenitor cells exist in the liver, are activated in various liver diseases and can form a potential target cell ...
The loss of #alpha#-globin gene transcriptional activity rarely occurs as an acquired abnormality during the evolution of myeloproliferative disease or preleukemia. To test whether the mutation responsible for the loss of #alpha#-globin gene expression (hemoglobin H disease) in these patients is linked with the #alpha#-globin genes on chromosome 16, the authors transferred chromosome 16 from preleukemic patients with acquired hemoglobin H disease to mouse erythroleukemia cells and measured the transcriptional activity of the human #alpha#-globin genes. After transfer to mouse erythroleukemia cells, the expression of human #alpha#-globin genes from the peripheral blood or marrow cells of preleukemic patients with acquired hemoglobin H disease was similar to that of human #alpha#-globin genes transferred to mouse erythroleukemia cells from normal donors. These ...
The patient positioning and repositioning control in radiation therapy all along the treatment can be conducted using a variety of X-ray sources and imaging detector devices. The development of image guided radiation therapy techniques leads to more frequent use of this imaging control. In this article we summarize the current methods for measuring the dose delivered by X-ray imaging devices used in radiation therapy, as well as basic proposals to take account of these imaging doses for prescribing, recording and reporting radiation therapy treatment. (authors)
AbstractBackground: So far, infliximab (IFX) therapy for the treatment of Crohn's disease (CD) has generally been guided by clinical symptoms. Data on treatment response as ascertained by endoscopy in IFX therapy are scarce. The aims of this study were to measure the endoscopic response rate during IFX induction and maintenance therapy in luminal CD, and also evaluate the role of endoscopy in monitoring IFX therapy. Methods: Data obtained from 71 patients with active luminal CD and treated with IFX were analyzed retrospectively. The endoscopy findings were scored according to mucosal activity as: 0 (remission), 1-2 (mild), 3-4 (moderate), and 5-6 (severe). A positive endoscopic response was determined by a decrease in score of at least two points and mucosal healing was assigned a score of...
Computational prediction of microRNA targets remains a challenging problem. The existing rule-based, data-driven and expression profiling approaches to target prediction are mostly approached from the...Full Text Available
In order to identify novel high value antibacterial targets it is desirable to delineate whether the inactivation of the target enzyme will lead to bacterial death or stasis. This knowledge is particularly...Full Text Available
Purpose: A retrospective analysis was undertaken to determine the indications for, the efficacy of, and the long-term complications of two courses of total skin electron beam therapy for mycosis fungoides. Methods and Materials: A retrospective analysis of 15 patients with the pathologic diagnosis of mycosis fungoides treated in the Department of Radiation Oncology at Stanford University Medical Center between 1968 and 1990 was performed. All patients received two courses of high-dose electron beam therapy to the skin. The mean dose for the total skin treatment for the first course was 32.6 Gy and 23.4 Gy for the second course of treatment. Results: Following the first course of total skin electron beam therapy, 11 of 15 had a complete response, with a mean duration of 11.6 months. All patients received adjuvant therapies between the first and second courses of high-dose total skin electron beam ...
Little clinical evidence has been provided to show the minimization of radiation resistance of tumors using high linear energy transfer radiation. We therefore investigated the radiobiological and molecular pathological aspects of carbon beam therapy. A total of 27 patients with squamous cell carcinoma (SCC) of the cervix were treated using a carbon beam and 50 control patients with SCC of the cervix using a photon beam. The expression of Ki-67, p53, and p27 proteins before radiotherapy and 5 and 15 days after therapy initiation were investigated using immunohistochemistry. Similar changes were observed in Ki-67 labeling index (LI) and p53 LI during carbon and photon beam therapies. However, for carbon beam therapy, the mean p27 LI significantly decreased from 25.2% before treatment to 18.6% on the 5th day after treatment initiation, followed by a significant increase to 36.1% on the 15th day. In ...
Radiation therapy has had a significant and an expanded role in the management of cancer of the pancreas during the last decade. In particular, for locally advanced disease, radiation therapy has improved the median survival of patients to 1 year. Intraoperative electron beam therapy has been applied to unresectable and resectable pancreatic cancer in an attempt to enhance local control of disease and to improve patient survival. This paper presents a survey of the role of radiation therapy in treatment of cancer of the pancreas, provides information on the radiobiological aspects of this treatment modality and details the physical and dosimetric characteristics of intraoperative radiation therapy with electrons. Presented are the design specifics of an applicator system, central axis beam data, applicator parameters, dose distribution data, shielding, treatment planning and means ...
Radiation therapy has had a significant and an expanded role in the management of cancer of the pancreas during the last decade. In particular, for locally advanced disease, radiation therapy has improved the median survival of patients to 1 year. Intraoperative electron beam therapy has been applied to unresectable and resectable pancreatic cancer in an attempt to enhance local control of disease and to improve patient survival. This paper presents a survey of the role of radiation therapy in treatment of cancer of the pancreas, provides information on the radiobiological aspects of this treatment modality and details the physical and dosimetric characteristics of intraoperative radiation therapy with electrons. Presented are the design specifics of an applicator system, central axis beam data, applicator parameters, dose distribution data, shielding, treatment planning and means ...
Computational fluid dynamics(CFD) code FLUENT was used to simulate the thermal hydraulic processes occurring in conceptual design of the accelerator-driven subcritical reactor(ADSR) liquid lead target. The purpose of the analysis is to investigate the thermal hydraulic characteristics of liquid lead as ADSR target material with various target geometries and injection locations of proton beam. In the calculation analysis, the local temperature of the liquid lead target rises to the boiling temperature very rapidly. When the proton beam is injected from the bottom of the target system, the duration time to reach the boiling temperature is longer and the temperature distribution is flatter than other cases.
Methods: Systemic irradiation of neuroaxis is an essential part in the management of medulloblastoma, stPNET and intracranial germ cell tumors. The introduction of quality assurance programs in radiooncology assures a precise radiotherapy of target volumes and is a prerequisite to improve survival. Results: Hyperfractionated radiotherapy has the potential of increasing dose to tumor more safely without increasing the risk for late adverse effects. Pilot studies revealed excellent tumor control in medulloblastoma with acceptable acute toxicity and a long-term survival of up to 96%. In medulloblastoma stereotactic radiation techniques reveal an acceptable toxicity and promising results in tumor control in recurrent disease or as primary treatment. They are now part of future treatment protocols in case of persisting residual tumor. Radiotherapy alone in pure germinoma is continuously yielding high cure rates. In secreting germ cell tumors cisplatin containing ...
Experimental and computational investigations were performed in order to better understand the mechanical response of rigid targets with various geometries to the detonation of shallow buried explosives. The motion of the targets was measured by use of high-speed digital video photography. This work involved flat targets, targets that were downwardly convex, and targets that were downwardly concave with explosive charges located at various positions beneath the targets. It was observed that, in general, angled hulls - whether downwardly concave or convex - tended to reduce the amount of momentum imparted to the center of mass of the targets. Computations were performed by use of an arbitrary Langrangian-Eulerian treatment in a nonlinear finite element code. A model based on quasi-static te...
In an effort to develop octahedral metal complexes as chemotherapeutic and diagnostic agents targeted to DNA, it is critical to optimize the properties of their cellular uptake. Appending d-octaarginine...Full Text Available
The design of the absorber blocks for internal and external dumping of the SPS proton beam is discussed. In addition, the external target stations for slow and fast extracted proton beams are described.
... L. Sutton. 2000. Is the aquatic weed hygrophila, Hygrophila polysperma (Polemoniales: Acanthaceae), a suitable target for classical biological ... ...
Nato SCI-12 on Camouflage Evaluation Workshop on Search and Target Acquisition The Netherlands, June 1999. Image Discrimination Models for Object Detection ...
By W. Wayne Scott. Langley Research Center. SUMMARY. Thin- and thick-target bremsstrahlung spectra are presented for electron energies up to 7.0 MeV. ...
Drosophila melanogaster has long been at the forefront of studies of transcriptional regulation in animals. Many fundamental ideas--such as cis control elements that act over long distances, the regulation of development by hierarchical cascades of transcription factors, dosage compensation, and position effect variegation--originated from studies of the fruit fly. The recent completion of the euchromatic DNA sequence of Drosophila is another breakthrough. The sequence data highlight important unanswered questions. For example, only one-fifth of the 124 Mb of Drosophila euchromatic DNA codes for protein. The function of the remaining 100 Mb of mostly unique DNA is largely unknown. Some proportion of this non-reading frame DNA must encode the functional recognition sites targeted by the approximately 700 sequence-specific DNA binding proteins that regulate transcription in Drosophila, but what proportion? Most or very little? Promoter sequences by definition contain ...
The human olfactomedin 4 gene (OLFM4) encodes an olfactomedin-related glycoprotein. OLFM4 is normally expressed in a limited number of tissues, including the prostate, but its biological functions in prostate are largely unknown. In this study, we found that OLFM4 messenger RNA was reduced or undetectable in prostate cancer tissues and prostate cancer cell lines. To study the effects of OLFM4 on prostate cancer progression, we transfected PC-3 prostate cancer cells with OLFM4 to establish OLFM4-expressing PC-3 cell clones. The OLFM4-expressing PC-3 cell clones were found to have decreased proliferation and invasiveness compared with vector-transfected control PC-3 cells in vitro. In addition, nude mice injected with OLFM4-expressing PC-3 cells demonstrated reduced tumor growth and bone invasion and metastasis compared with mice injected with vector-transfected control cells. Mechanistic studies revealed that OLFM4 may exhibit its anticancer effects through ...
Endocrine disrupting chemicals can induce malformations and impairment of reproductive function in experimental animals and may have similar effects in humans. Recently, the environmental obesogen hypothesis was proposed, suggesting that environmental chemicals contribute to the development of obesity and insulin resistance. These effects could be related to chemical interaction with nuclear receptors such as the peroxisome proliferator activated receptors (PPARs). As several testosterone-reducing drugs are PPAR activators, we aimed to examine whether four PPAR agonists were able to affect fetal testosterone production and masculinization of rats. Additionally, we wished to examine whether these chemicals affected fetal plasma levels of insulin and leptin, which play important roles in the developmental programming of the metabolic system. Pregnant Wistar rats were exposed from gestation day (GD) 7-21 to diisobutyl phthalate (DiBP), butylparaben, perfluorooctanoate, or rosiglitazone ...
Pancreatitis-associated protein (PAP) is a secretory pancreatic protein present in small amounts in normal pancreas and overexpressed during the acute phase of pancreatitis. In this paper, the authors describe the cloning, characterization, and chromosomal mapping of the human PAP gene. The gene spans 2748 bp and contains six exons interrupted by five introns. The gene has a typical promoter containing the sequences TATAAA and CCAAT 28 and 52 bp upstream of the cap site, respectively. They found striking similarities in genomic organization as well as in the promoter sequences between the human and rat PAP genes. The human PAP gene was mapped to chromosome 2p12 using rodent-human hybrid cells and in situ chromosomal hybridization. This localization coincides with that of the reg/lithostathine gene, which encodes a pancreatic secretory protein structurally ...
The National Ignition Facility (NIF) is a proposed Department of Energy facility which will contribute to the resolution of important Defense Program and inertial fusion energy issues for energy production in the future. The NIF will consist of a laser system with 192 independent beamlets transported to a target chamber. The target chamber is a multi-purpose structure that provides the interface between the target and the laser optics. The chamber must be capable of achieving moderate vacuum levels in reasonable times; it must remain dimensionally stable within micron tolerances, provide support for the optics, diagnostics, and target positioner; it must minimize the debris from the x-ray and laser light environments; and it must be capable of supporting external neutron shielding. The chamber must also be fabricated from a low neutron activation material. The fusion reaction in the ...
To gain insight into the changes in the transcriptome of soybean roots during soybean cyst nematode (SCN) infection, we conducted genome-wide gene expression profiling using serial analysis of gene expression (SAGE) combined with Solexa sequencing. More than 3 million tags were generated from the SCN-infected and uninfected roots, and 366941 and 314591 clean UniTags were obtained from SCN-infected and uninfected samples, respectively. In the SCN-infected sample, 48249 UniTags represented 18114 reference genes. In the uninfected control, 46290 UniTags represented 19323 reference genes. Comparison of tag frequencies identified 1405 genes that were expressed at greater levels in SCN-infected roots than in uninfected roots, and 1191 genes that were expressed at lower levels. Quantitative real-...
Purpose/Objective: With the advent of computed tomography and magnetic resonance imaging, the three dimensional representation of the patient anatomy has become an invaluable resource for better diagnosis and delineation of the target volume and sensitive structures in radiation therapy. Although the therapeutic linear accelerator industry has made available highly sophisticated equipment, the aggressiveness in dose prescription and delivery has to be complimented by accurate dose computation methods. We have adopted a convolution/superposition algorithm for the calculation of absolute dose that fully accounts for the external shape and internal structure of the patient for photon treatment radiotherapy. In this paper, we will discuss the principles of the convolution algorithm and we will show how the computed dose compares to clinically relevant treatment techniques. Materials and Methods: A computer controlled data acquisition system and a ...
We proposed a solid and a mercury target concepts through the preliminary conceptual design. To feasible these concepts, analysis and experimental works are being carried out. This paper introduces an outline of present status of target R and D such as heat transfer augmentation experiments for the solid target, mercury flow tests with a loop of maximum flow rate of 15L/min, flow pattern measurements for a cold source moderator etc. as well as preliminary conceptual design works. (author)
In the CERN approach to the design of a neutrino factory, the repetition frequency of the proton beam is high enough to consider stationary solid targets as a viable solution for multi-MW beams. The target consists of high density tantalum spheres of 2 mm diameter which can efficiently be cooled by passing a high mass flow He-gas stream through the voids between the Ta-granules. Very small thermal shocks and stresses will arise in this fine grained structure due to the relatively long burst of 3.3 ms from the SPL-proton linac. In a quadruple target system where each target receives only one quarter of the total beam power of 4 MW, conservative temperature levels and adequate lifetimes of the target are estimated in its very high radiation environment. A conceptual design of the integration of the target into the magnetic horn-pion-collector is presented.
For over 50 years, electron beams have been an important modality for providing an accurate dose of radiation to superficial cancers and disease and for limiting the dose to underlying normal tissues and structures. This review looks at many of the important contributions of physics and dosimetry to the development and utilization of electron beam therapy, including electron treatment machines, dose specification and calibration, dose measurement, electron transport calculations, treatment and treatment-planning tools, and clinical utilization, including special procedures. Also, future changes in the practice of electron therapy resulting from challenges to its utilization and from potential future technology are discussed. (review)
Prostate cancer can be successfully treated using dynamic adaptive external beam radiation techniques along with interstitial brachytherapy to deliver curative therapies with low urinary, rectal and erectile function morbidity. Through the use of sophisticated, state-of-the art radiographic imaging for staging and treatment planning, a precise, individual design for treatment is accomplished. Symptom management and patient education are of paramount importance and are integrated throughout the treatment process.
BackgroundMicroarray studies can supplement QTL studies by suggesting potential candidate genes in the QTL regions, which by themselves are too large to provide a limited selection...Full Text Available
Extending genome wide association analysis by the inclusion of gene expression data may assist in the dissection of complex traits. We examined piebald, a pigmentation phenotype in both human and Merino...Full Text Available
The use of Sleeping Beauty transposons as somatic mutagens to discover cancer genes in hematopoietic tumors and sarcomas has been documented. Here, we discuss the future of Sleeping...Full Text Available
BackgroundDinoflagellates are unicellular, often photosynthetic protists that play a major role in the dynamics of the Earth's oceans and climate. Sequencing of dinoflagellate nuclear...Full Text Available
A regional analysis of nucleotide substitution rates along human genes and their flanking regions allows us to quantify the effect of mutational mechanisms associated with transcription in germ line...Full Text Available
Highly polymorphic genes with central roles in lymphocyte mediated immune surveillance are grouped together in the major histocompatibility complex (MHC) in higher vertebrates. Generally, across vertebrate...Full Text Available
Rhizobium leguminosarum, biovar viceae, strain RCC1001 contains two glutamine synthetase activities, GSI and GSII. We report here the identification of glnA, the structural gene for GSI. A 2 kb fragment...Full Text Available
Ecological speciation is the process by which barriers to gene flow between populations evolve due to adaptive divergence via natural selection. A relatively unexplored area in ecological speciation...Full Text Available
We have previously reported the construction and characterization of an autonomously replicating plasmid in Trypanosoma brucei. In this plasmid the procyclic acidic repetitive protein (PARP) gene promoter...Full Text Available
Although recent data established that a specific very-long-chain fatty acyl-CoA synthetase is defective in X-linked adrenoleukodystrophy (ALD), the ALD gene is still unidentified. The ALD locus has...Full Text Available
OBJECTIVETo determine if ProL1, a member of the opiorphin family of genes, can modulate erectile physiology, as it encodes a peptide which acts as...Full Text Available
BackgroundWhile the gene flow in some organisms is strongly affected by physical barriers and geographical distance, other highly mobile species are able to overcome such constraints....Full Text Available
BackgroundHigh complexity is considered a hallmark of living systems. Here we investigate the complexity of temporal gene expression patterns using the concept of Permutation Entropy...Full Text Available
A series of deletion mutants extending from -250 toward the capsite has been constructed in the early promoter region of the adenovirus 2 EIIa gene and tested both in vitro, and in vivo after transfection...Full Text Available
Many of the gene products that participate in nitrogen metabolism are sensitive to nitrogen catabolite repression (NCR), i.e., their expression is decreased to low levels when readily used nitrogen...Full Text Available
BackgroundDue to the increased accuracy of Copy Number Variable region (CNV) break point mapping, it is now possible to say with a reasonable degree of confidence whether a gene...Full Text Available
In many dinoflagellate species, the plastid genome has been proposed to exist as a limited number of single-gene minicircles, and many genes normally found in the plastid genome are nuclear-encoded....Full Text Available
PurposeIt has been demonstrated that mutations in deafness, autosomal recessive 31 (DFNB31), the gene encoding whirlin, is responsible for nonsyndromic hearing loss...Full Text Available
The official name of this gene is "solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 4." SLC25A4 is the gene's official symbol. The...
BackgroundCalcitonin gene related peptide (CGRP) is a neuropeptide that is abundant in the sensory neurons which innervate bone. The effects of CGRP on isolated bone cells have been...Full Text Available
The DUR3 gene, which encodes a component required for active transport of urea in Saccharomyces cerevisiae, has been isolated, and its sequence has been determined. The deduced DUR3 protein profile...Full Text Available
Brown fat is a specialized tissue that can dissipate energy and counteract obesity through a pattern of gene expression that greatly increases mitochondrial content and uncoupled respiration. PRDM16...Full Text Available
Gene expression is a unique way of characterizing how cells and organisms adapt to changes in the external environment. The measurements of gene expression levels upon exposure to a chemical can be...Full Text Available
Genomic disorders are conditions that result from DNA rearrangements, such as deletions or duplications. The identification of the dosage-sensitive gene(s) within the rearranged genomic interval is...Full Text Available
BackgroundIn cancer research, the association between a gene and clinical outcome suggests the underlying etiology of the disease and consequently can motivate further studies. The...Full Text Available
Dissecting the genes involved in complex traits can be confounded by multiple factors, including extensive epistatic interactions among genes, the involvement of epigenetic regulators, and the variable...Full Text Available
BackgroundWith the advent of increasingly efficient means to obtain genetic information, a great insurgence of data has resulted, leading to the need for methods for analyzing this...Full Text Available
BackgroundPolymorphisms in Epidermal Growth Factor Receptor (EGFR) gene may influence EGFR production and/or activity, thereby modulating susceptibility to lung...Full Text Available
Orthologous positions of 55 genes associated with height in four human populations were located on the bovine genome. Single nucleotide polymorphisms close to eight of these genes were significantly...Full Text Available
Generations 5 and 6 (G5 and G6) poly(amidoamine) (PAMAM) dendrimers have been shown to be highly efficient nonviral carriers in in vitro gene delivery. However, their high toxicity...Full Text Available
In order to efficiently utilize natural cellulose materials to produce ethylene, three expression vectors containing the ethylene-forming enzyme (efe) gene from Pseudomonas...Full Text Available
Ever since the pre-molecular era, the birth of new genes with novel functions has been considered to be a major contributor to adaptive evolutionary innovation. Here, I review the origin and evolution...Full Text Available
BackgroundGene promoters can be in various epigenetic states and undergo interactions with many molecules in a highly transient, probabilistic and combinatorial way, resulting in...Full Text Available
Noncoding RNAs play important roles in various aspects of gene regulation. We have identified 7SK RNA to be enriched in nuclear speckles or interchromatin granule clusters (IGCs), a subnuclear domain...Full Text Available
Male transgenic mice expressing the polyomavirus middle T (PyV-MT) gene exhibited growth and developmental abnormalities in prostatic and other urogenital epithelium. Expression of PyV-MT was directed...Full Text Available
PurposeTo investigate whether acquired somatic mutations in the iron response element of the ferritin L-chain gene account for the age-related cataract.MethodsThe...Full Text Available
Vulnerability to abused drugs is influenced by multiple genes unique to each drug as well as to risk genes for polydrug abuse. If several inbred mouse strains respond to different drugs similarly,...Full Text Available
PurposeThe size of neuronal populations is modulated by gene variants that influence cell production and survival, in turn influencing neuronal connectivity, function,...Full Text Available
Goosecoid is a homeobox gene first isolated from a Xenopus dorsal lip cDNA library. Homologous genes have been isolated from mouse, zebrafish, and chick. In all species examined, the gene is expressed and plays an important role during the process of gastrulation in early embryonic development. The authors report here the cloning of the human goosecoid (GSC) from a genomic library and the sequence of its encoded protein. The genomic organization and protein sequence of the human gene are highly conserved with respect to those of its Xenopus and mouse counterparts: all three genes consist of three exons, with conserved exon-intron boundaries. The sequence of the homeo-domain is 100% conserved in most vertebrates. Using somatic cell hybrid and chromosomal in situ hybridization, the gene was mapped to chromosome 14q32.1. 30 refs., 3 figs., 2 tabs.
This article describes the molecular cloning and expression of a hemolysin gene from a serotype 1 strain of Actinobacillus pleuropneumoniae. The hemolysin was a thermolabile protein with an apparent...Full Text Available
Hormone potency depends on receptor availability, regulated via gene expression and receptor trafficking. To ascertain how central leptin receptors are regulated, the effects of leptin challenge, high-fat...Full Text Available
Exploring the possibility of enhancing the properties of baculoviruses as biological control agents of insect pests, we tested the effect of expressing an insect gene (jhe) encoding juvenile hormone...Full Text Available
Major histocompatibility complex (MHC) genes are highly polymorphic components of the vertebrate immune system, which play a key role in pathogen resistance. MHC genes may also function as odour-related...Full Text Available
BackgroundModern approaches to treating genetic disorders, cancers and even epidemics rely on a detailed understanding of the underlying gene signaling network. Previous work has...Full Text Available
Activation-induced cytidine deaminase (AID) protein initiates Ig gene mutation by deaminating cytosines, converting them into uracils. Excision of AID-induced uracils by uracil-N-glycosylase...Full Text Available
IntroductionPrevious observations suggest that active systemic juvenile idiopathic arthritis (sJIA) is associated with a prominent erythropoiesis gene-expression signature. The aim...Full Text Available
Isogenic strains containing insertional disruptions of 10 Haemophilus influenzae Rd genes were investigated for their effects on the susceptibility of the organism to various classes...Full Text Available
BackgroundGene regulation is a key mechanism in higher eukaryotic cellular processes. One of the major challenges in gene regulation studies is to identify regulators affecting the...Full Text Available
A mutation in a new gene, molR, prevented the synthesis in Escherichia coli of molybdoenzymes, including the two formate dehydrogenase isoenzymes, nitrate reductase and trimethylamine-N-oxide reductase....Full Text Available
Cellular hypertrophy is regulated by coordinated pro- and antigrowth machineries. Foxo transcription factors initiate an atrophy-related gene program to counter hypertrophic growth. This study was designed...Full Text Available
The DNA sequences were determined for the lipoprotein lipase (LPL) gene from five unrelated Japanese patients with familial LPL deficiency. The results demonstrated that all five patients are homozygotes...Full Text Available
The Drosophila hairy gene encodes a basic helix- loop-helix protein that functions in at least two steps during Drosophila development: (1) during embryogenesis, when it partakes in the establishment of segments, and (2) during the larval stage, when it functions negatively in determining the pattern of sensory bristles on the adult fly. In the rat, a structurally homologous gene (RHL) behaves as an immediate-early gene in its response to growth factors and can, like that in Drosophila, suppress neuronal differentiation events. Here, the authors report the genomic cloning of the human hairy gene homolog (HRY). The coding region of the gene is contained within four exons. The predicted amino acid sequence reveals only four amino acid differences between the human and rat genes. Analysis of the DNA sequence 5[prime] to the coding region reveals a putatitve ...
A genomic clone that specifies a single polypeptide precursor for ricin, a toxic lectin of Ricinus communis (castor bean), was isolated, sequenced and Sl mapped. The gene encodes a 64 kDa precursor...Full Text Available
BackgroundDue to the high morbidity and mortality of fulminant hepatitis, early diagnosis followed by early effective treatment is the key for prognosis improvement. So far, little...Full Text Available
The National Cancer Institute Laboratory of Human Carcinogenesis is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize a gene signature for prognosis of hepatocellular carcinoma in patients.
Two heterologous expression systems using thioredoxin (trxA) as a gene fusion part in Escherichia coli were developed to produce recombinant pediocin PA-1. Pediocin...Full Text Available
Multiple discrete regions at 8q24 were recently shown to contain alleles that predispose to many cancers including prostate, breast, and colon. These regions are far from any annotated gene and their...Full Text Available
The availability of full genome sequences has allowed the construction of microarrays, with which screening of the full genome for changes in gene expression is possible. This method can provide a wealth...Full Text Available
The results of a study of the expression of embryonic hemoglobin genes in mice which show an imbalance of alpha and non-alpha chain synthesis are reported. (ACR)
Pseudomonas mandelii liquid cultures were studied to determine the effect of pH and temperature on denitrification gene expression, which was quantified by quantitative reverse transcription-PCR....Full Text Available
Systemic administration of lipopolysaccharide (LPS), which causes endotoxemia and systemic inflammation, has been reported to induce expression of the gene for type II inducible nitric oxide synthase...Full Text Available
BackgroundInformation on more than 35 000 full-length Oryza sativa cDNAs, together with associated microarray gene expression data collected under various treatment...Full Text Available
BackgroundThe bacterial genus Listeria contains pathogenic and non-pathogenic species, including the pathogens L. monocytogenes and L. ivanovii,...Full Text Available
As many as 59% of the transcription factors in Escherichia coli regulate the transcription rate of their own genes. This suggests that auto-regulation has one or more important...Full Text Available
We cloned and sequenced structural gene choM, which encodes an insecticidally active cholesterol oxidase in Streptomyces sp. strain A19249. The primary translation product was predicted to be a 547-amino-acid...Full Text Available
The regulation of gene expression in the brain reward regions is known to contribute to the pathogenesis and persistence of drug addiction. Increasing evidence suggests that the regulation of gene transcription...Full Text Available
BackgroundThe rate of emergence of human pathogens is steadily increasing; most of these novel agents originate in wildlife. Bats, remarkably, are the natural reservoirs of many...Full Text Available
BackgroundMembers of the Sox gene family isolated from both vertebrates and invertebrates have been proved to participate in a wide variety of developmental processes, including...Full Text Available
The F1F0 ATPase of Vibrio alginolyticus was cloned from a chromosomal lambda library. The unc operon, which contains the structural genes for the ATPase, was sequenced and shown to have a gene organization...Full Text Available
Recombinant mouse UDP-glucose pyrophosphatase (UGPPase), encoded by the Nudt14 gene, was produced in Escherichia coli and purified close to homogeneity. The...Full Text Available
The molecular diversity of the gene encoding the outer membrane protein A (OmpA) of Haemophilus parasuis has been unclear. In this study, the structural characteristics, sequence types,...Full Text Available
Comparative sociogenomics has the potential to provide important insights into how social behaviour evolved. We examined brain gene expression profiles of the primitively eusocial wasp Polistes...Full Text Available
Antisense radiopharmaceuticals could be used to image gene expression in the brain in vivo, should these polar molecules be made transportable through the blood–brain barrier....Full Text Available
A sensitive and specific detection method was developed for Xanthomonas hyacinthi; this method was based on amplification of a subsequence of the type IV fimbrial-subunit gene fimA...Full Text Available
BackgroundGenomics has substantially changed our approach to cancer research. Gene expression profiling, for example, has been utilized to delineate subtypes of cancer, and facilitated...Full Text Available
Rapid development in genomics in recent years has allowed the simultaneous measurement of the expression levels of thousands of genes using DNA microarrays. This has offered tremendous potential...Full Text Available
The aim of this study was to survey the expression of an embryonic cytokine gene, MK, in the normal organs and neoplastic tissues of adults. Northern analysis showed that MK mRNA was exclusively expressed...Full Text Available
From Toki-shakuyaku-san, an herbal formulation for “cleansing stagnated blood,” a key gene regulatory compound was purified and identified through a screening based on DNA microarray...Full Text Available
BackgroundWe have recently introduced a predictive framework for studying gene transcriptional regulation in simpler organisms using a novel supervised learning algorithm called...Full Text Available
During complementary chromatic adaptation (CCA), cyanobacterial light harvesting structures called phycobilisomes are restructured in response to ambient light quality shifts. Transcription of genes...Full Text Available
Gene expression profiling has played an important role in cancer risk classification and has shown promising results. Since gene expression profiling often involves determination of a set of...Full Text Available
For identification of genes responsible for varietal differences in flowering time and leaf morphological traits, we constructed a linkage map of Brassica rapa DNA markers including...Full Text Available
Synthetic complementary oligonucleotides are useful hybridization probes for the detection of mRNAs and genes encoding proteins for which only a partial amino acid sequence is known. Usually this involves...Full Text Available
Innovative therapy may appear to coincide with medical experimentation, raising ethical and legal issues, for instance on informed consent and institutional review. Medical treatments may be classified,...Full Text Available
Background and ObjectivePulsed dye laser (PDL) treatment of cutaneous vascular lesions is associated with variable and unpredictable efficacy. Thus, alternative treatment...Full Text Available
Objectives: Acupuncture has served as a major complementary and alternative therapy that supplements conventional medicine and is the subject of growing public interest. This study was conducted to estimate the usage rate of acupuncture as a supplemental treatment in acute ischaemic stroke patients and to identify factors associated with the choice to use this therapy. Methods: Using the registry of stroke patients admitted to an academic medical centre in Korea, the use of acupuncture therapy was recorded and analysed, along with the patients' socio-demographic characteristics, hospital access variables, risk factors for ischaemic stroke and clinical characteristics. The data were analysed using descriptive statistics, chi-square tests and multiple logistic regression analyses. Results: O...
Mycosis fungoides (MF) in deep-seated lymph nodes, spleen or liver appears to be associated with a lack of response of the disease to topical external therapy. Fourteen patients with mycosis fungoides...Full Text Available
Summary: The increasing emergence of antimicrobial-resistant organisms, especially methicillin-resistant Staphylococcus aureus (MRSA), has resulted in the increased...Full Text Available
Structured abstractObjectiveAlthough most reviews of Pseudomonas aeruginosa therapeutics focus on antibiotics currently in use or...Full Text Available
Penile rehabilitation therapy following radical prostatectomy is a much debated topic. Erectile dysfunction is still a significant contributor to postoperative morbidity following radical prostatectomy, despite meticulous nerve-sparing technique. Secondary smooth muscle changes in the penis have been identified as the underlying causes of penile atrophy, veno-occlusive dysfunction, and fibrosis. Initial observations that intracavernous injection therapies used on a regular basis postoperatively resulted in improvements in the return of spontaneous erectile function led to the development of penile rehabilitation protocols. Chronic dosing of PDE-V inhibitors is now commonly used by urologists after radical prostatectomy. Despite the current enthusiasm of penile rehabilitation therapy, current scientific evidence with clinical trials is still limited. PMID:19255627
PurposeTo identify the extent of persistence (period of time of continuous therapy with the drug prescribed) of glaucoma patients treated with prostaglandins (latanoprost, bimatoprost,...Full Text Available
BackgroundStump and phantom pains are debilitating sequelae of amputations that are often resistant to treatment. The efficacy of pharmacologic therapies, including...Full Text Available
Modern advances in the concept and the techniques of megavoltage radiation therapy have revolutionized the treatment of medulloblastoma. Five-year survivals of 50 to 70 percent are achieved by craniospinalaxis...Full Text Available
BackgroundLymphangioleiomyomatosis (LAM) is a rare lung disease characterised by progressive airflow obstruction. No effective medical treatment is available but therapy with sirolimus...Full Text Available
SYNOPSISPreterm infants are at risk for both iron deficiency and iron overload. The role of iron in multiple organ functions suggests that iron supplementation is essential for...Full Text Available
Hyperglycemia frequently occurs with acute medical illness, especially among patients with cardiovascular disease, and has been linked to increased morbidity and mortality in critically ill patients....Full Text Available
Invasive fungal infections can be devastating, particularly in immunocompromised patients, and difficult to treat with systemic drugs. Furthermore, systemic administration of those medications...Full Text Available
Development of Portable Normobaric Hypoxia and Pulsed Magnetic Field Firmware System for Enhancement of Radio- and Non-specific Resistance in Workers of Environmentally Hazardous Industries
An elderly man receiving chlorambucil for chronic lymphatic leukaemia developed focal fits. The onset and frequency were dose related. There was no evidence of metabolic disturbance or of meningeal...Full Text Available
The clinical results of electron beam therapy using intraoral cone in 8 cases of primary and recurrence carcinoma of tongue (T1 and smaller T2) were reported. The primary and recurrence cases were 5 and 3, respectively. In the 5 cases, a total dose of 10-30 Gy external radiation therapy were combined prior to electron beam therapy. The total dose of electron beam therapy varied from 40 to 60 Gy. In all cases, tumor showed good response and disappeared clinically. Radiation stomatitis, pain of the tongue with masticatory disturbance due to tenderness were complicated in all cases. These complications gradually disappeared 2 to 6 months after treatment. However, loss of body weight and bone exposure were not recognized in any case. Intraoral-cone electron beam therapy is thought to be available and has less complications comparing interstitial irradiation therapy ...
BackgroundTo investigate the effects of intravenous lignocaine infusions (IV lignocaine) in fibromyalgia.MethodsProspective study...Full Text Available
SynopsisAttention-deficit / hyperactivity disorder (ADHD) is a valid and impairing psychological disorder that persists into adulthood in a majority of cases and is associated...Full Text Available
BackgroundAlthough advances in rehydration therapy have made cholera a treatable disease with low case-fatality in settings with appropriate medical care, cholera continues...Full Text Available
... mammography or on ultrasound but not found on physical examination, we consider them non-palpable or not ... lot of this. We send every patient for physical therapy, no matter what type of reconstruction we ...
Previous research with individuals undergoing surgery or diagnostic procedures provided a conceptual framework for analysis of radiation therapy, a common form of cancer treatment. The present...Full Text Available
Antimony toxicity occurs either due to occupational exposure or during therapy. Occupational exposure may cause respiratory irritation, pneumoconiosis, antimony spots on the skin and gastrointestinal...Full Text Available
Adaptive radiation therapy for liver cancer has the potential to reduce normal tissue complications and enable dose escalation, allowing the potential for tumor control in this challenging site....Full Text Available
BackgroundAdequate pain assessment is critical for evaluating the efficacy of analgesic treatment in clinical practice and during the development of new therapies. Yet the currently...Full Text Available
The objective of this animation is to develop a QTL mapping population for locating and characterizing the genes responsible for resistance to tan spot disease of wheat.
Objectives: The purpose of this work was to study the genetic determinants responsible for extended-spectrum beta-lactamase (ESBL) resistance of Salmonella isolated from Dutch poultry, poultry meat and hospitalized humans. Methods: Thirty-four ESBL-resistant Salmonella isolates from The Netherlands were tested towards 21 antimicrobial agents. PCR and sequencing were used to determine the underlying genetic determinants responsible for the ESBL phenotypes. The transferability of the ESBL phenotypes was tested by conjugation to a susceptible Salmonella enterica serovar Dublin and plasmid purification, restriction fragment length polymorphism (RFLP) and pulsed-field gel electrophoresis (PFGE) were employed to further characterize a subset of the isolates. Results: A great genetic diversity was seen among the isolates. The bla(TEM-52) gene was most predominant and was found among Salmonella enterica serovars Blockley, Thomson, London, Enteritidis phage type 14b, ...
Lethal alleles of the Drosophila k43 gene result in small or missing imaginal discs, greatly reduced mitotic index, and fragmented and abnormally condensed chromosomes. A female-sterile...Full Text Available
The products of trithorax group (trxG) genes maintain active transcription of many important developmental regulatory genes, including homeotic genes. Several trxG proteins have been shown to act in...Full Text Available
We have identified two novel, very closely related genes, SAS1 and SAS2, from Dictyostelium discoideum. These encode small, approximately 20-kilodaton proteins with amino acid sequences thought to be...Full Text Available
We demonstrate that expression of the UGA1, CAN1, GAP1, PUT1, PUT2, PUT4, and DAL4 genes is sensitive to nitrogen catabolite repression. The expression of all these genes, with the exception of UGA1...Full Text Available
The organization of lin genes and IS6100 was studied in three strains of Sphingomonas paucimobilis (B90A, Sp+, and UT26) which degraded hexachlorocyclohexane...Full Text Available
BackgroundThe large sensitivity, high reproducibility and essentially unlimited dynamic range of real-time PCR to measure gene expression in complex samples provides the opportunity...Full Text Available
Fission yeast S. pombe is assumed to be a good model for cloning of human DNA repair genes, because human gene is normally expressed in S. pombe and has a very similar protein sequence to yeast protein. We have tried to elucidate the DNA repair mechanisms of S. pombe as a model system for those of mammals. (J.P.N.)
Studies of flower development in core eudicot species have established a central role for B class MADS-box genes in specifying petal and stamen identities. Similarly in maize and rice, B class genes...Full Text Available
Loss-of-function mutations in the regulatory gene areA of Aspergillus nidulans prevent the utilization of a wide variety of nitrogen sources. The phenotypes of nit-2 mutants of Neurospora crassa suggest...Full Text Available
BackgroundGene mutation is an important mechanism of myeloid leukemogenesis. However, the number and combination of gene mutated in myeloid malignancies is still a matter of investigation.MethodsWe...Full Text Available
Low cytotoxicity and high gene transfection efficiency are critical issues in designing current non-viral gene delivery vectors. The purpose of the present work was to synthesize the novel biodegradable...Full Text Available
BackgroundThe mitochondrial genome of the Octocorallia has several characteristics atypical for metazoans, including a novel gene suggested to function in DNA repair. This mtMutS...Full Text Available
AbstractBackground: A defective innate immune response may contribute to the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). Employing a global gene expression analysis, this study was aimed at identifying specifically regulated genes within the epithelial compartment in inflammatory bowel disease (IBD). Methods: The epithelial fraction of human ileal mucosa samples from surgical specimens was obtained by laser microdissection. Gene expression was examined by global expression profiling (n = 18, Affymetrix), quantitative reverse-transcription polymerase chain reaction (RT-PCR) (n = 35), immunoblot analysis (n = 9), and immunohistochemistry (n = 25). Results: Global expression profiling revealed a pronounced downregulation of the retinoic acid-inducible gene I (RIG-I) with...
The efficiency of dendrosome (a gene porter) was assessed in transferring recombinant human rotavirus VP2 cDNA into A549, a human lung cell line. After gene transferring, transmission electron microscopy showed core-like particles (CLPs) formation in the transfected cells both with dendrosome and lipofectamine porters. In addition, western blotting analysis showed that the expression of VP2 gene was almost equal in the dendrosome and lipofectamine-transfected cells. Also, the cytotoxicity studies revealed that dendrosome had a lower cytotoxicity than lipofectamine. Therefore, our study may introduce dendrosome as a possible carrier for gene transferring into the human lung cell line, especially, for intranasally administration of DNA vaccines.
BACKGROUND: It was previously reported that dendrosomes, i.e. neutral, biodegradable, covalent or self-assembled, hyperbranched, spheroidal nano-particles with a size ranging from 15 to 100 nm, provide a convenient and efficient means of gene delivery into various kinds of cells such as human hepatoma and kidney cells as well as animal models.RESULTS: New studies via circular dichroism show that hydrophilic and amphipathic dendrosomes either do not affect the DNA structure or moderately transform it from B- to A-conformation. Gene delivery into human liver, kidney, and endothelial cells as well as other animal cells like Bowes, U-937, Raw, CCRF-CEM, MOLT-4, K562, Huh-7 and VERO reveal that the genes are efficiently expressed and in comparison with other gene porters like Lipofectin or bact...
The relationship between X chromosome-linked adrenoleukodystrophy and the red/green color pigment gene cluster on Xq28 was investigated in a large kindred. The DNA in a hemizygous male showed altered restriction fragment sizes compatible with at least a deletion extending from the 5[prime] end of the color pigment genes. Segregation analysis using a DNA probe within the color pigment gene cluster showed significant linkage with adrenoleukodystrophy (logarithm of odds score of 3.19 at [theta] = 0.0). These data demonstrate linkage, rather than association, between a unique molecular rearrangement in the color pigment gene cluster and adrenoleukodystrophy. The DNA changes in this region are thus likely to be helpful for determining the location and identity of the responsible gene. 33 refs., 4 figs.
We determined the chromosomal localization and structure of the gene encoding human type II inosine 5{prime}-monophosphate dehydrogenase (IMPDH, EC 1.1.1.205), an enzyme associated with cellular proliferation, malignant transformation, and differentiation. Using polymerase chain reaction (PCR) primers specific for type II IMPDH, we screened a panel of human-Chinese hamster cell somatic hybrids and a separate deletion panel of chromosome 3 hybrids and localized the gene to 3p21.1{yields}p24.2. Two overlapping yeast artificial chromosome clones containing the full gene for type II IMPDH were isolated and a physical map of 117 kb of human genomic DNA in this region of chromosome 3 was constructed. The gene for type II IMPDH was localized and oriented on this map and found to span no more than 12.5 kb.
Abstract Sudden infant death syndrome (SIDS) is always a devastating and unexpected occurrence. SIDS is the leading cause of death in the first 6 months after birth in the industrialized world. Since the discovery in 1998 of long QT syndrome as an underlying substrate for SIDS, around 10-20% of SIDS cases have been proposed as being caused by genetic variants in either ion channel or ion channel-associated proteins. Until now, 10 cardiac channelopathy susceptibility genes have been found to be implicated in the pathogenesis of SIDS. Four of the genes encode cardiac ion channel a-subunits, 3 genes encode ion channel b-subunits, and 3 genes encode other channel-interacting proteins. All 10 genes have been associated with primary electrical heart diseases. SIDS may hereby be the initial sympt...