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At least 1,297 records · Page 72Linked to original sources
PubMed2002

Gene amplification profiling of esophageal squamous cell carcinomas by DNA array CGH.

Gene amplification is one of the basic mechanisms that lead to overexpression of oncogenes. DNA array comparative genomic hybridization (CGH) has great potential for comprehensive analysis of both a relative gene-copy number and altered chromosomal regions in cancers, which enables us to identify new amplified genes and unstable chromosomal loci. We examined the amplification status in 32 esophageal squamous cell carcinomas (ESCCs) and 13 ESCC cell lines on 51 frequently amplified loci in a variety of cancers by both DNA array CGH and Southern blot analyses. The 1p34 locus containing MYCL1, 2p24 (MYCN), 7p12 (EGFR), and 12q14 (MDM2) were amplified in one of the 32 cases (3%), and the 17q12 locus (ERBB2) and 8p11 (FGFR1) in two of the 32 cases (6%), while only the 11q13 locus (Cyclin D1, FGF4, and EMS1) was frequently amplified (28%, 9/32), demonstrating this locus to be a major target in ESCCs. One locus, 8q24 (c-MYC) was found to be amplified only in the cell lines. Eight out of 51 loci (15.7%) were found to be amplified in at least one of the 32 primary ESCCs or the 13 ESCC cell lines, suggesting that chromosomal loci frequently amplified in a type of human cancer may also be amplified in other types of cancers. This paper is the first report of an application of DNA array CGH to ESCCs.

Blotting, Southern↗
PubMed2002

Genomic responses to herbal extracts: lessons from in vitro and in vivo studies with an extract of Ginkgo biloba.

Do herbal extracts offer effective dietary supplements to prevent deregulation of the transcriptome? Can they normalize deregulated transcriptomes of chronic human diseases? Are the effects of herbal extracts targeted to specific molecular pathways in tissue-specific manner? Are the effects of herbal supplements reversible? These questions pose important challenges to the fields of molecular nutrition and medicine, which are committed to understanding the molecular basis of physiology during health and disease. Transcription of the molecular information encoded in the deoxynucleotide sequences of DNA to the nucleotide sequences of RNA play a vital, causative, role in the coordinated adaptation of the organism to its changing environment and its nutritional needs. Pathogenesis is a manifestation of defects in transcription of the genome. Herbal extracts may target these obligatory processes. Increased availability of tools for quantitative and comprehensive analysis of messenger RNAs offer powerful means to understand and identify changes in these fundamental processes. Studies with the extract of Ginkgo biloba leaves show that the extract affects transcription of functionally diverse groups of genes in vitro and in vivo. The observations offer molecular evidence for bioactivity of the extract and offer an analytical strategy to define and predict physiological effects of complex mixtures of phytochemicals.

Animals↗
PubMed2000

Diurnal metabolism of dopamine in the mouse retina.

Dopamine is an important retinal neurotransmitter and neuromodulator that regulates key diurnal cellular and physiological functions. In the present study we carried out a comprehensive analysis of dopamine metabolism during the light phase of the diurnal cycle and evaluated the presence of diurnal and circadian rhythms of dopaminergic activity in the mouse retina. Steady-state levels of dopamine did not change significantly between the dark phase (night) and the light phase (day) of the diurnal cycle, nor did they change between early and late points in the day. Dopamine synthesis and utilization, however, revealed significant alterations between the night and day and between early and late time points in the day. A spike in synthesis and utilization was measured immediately after light onset at the end of the night. Subsequently, dopamine synthesis and utilization partially declined and remained stable throughout the remainder of the day at a level that was significantly higher than that at night. The burst of dopamine synthesis and utilization at the beginning of the day is entirely light evoked and not driven by a circadian clock. Similarly, there was no circadian rhythm in dopamine synthesis and utilization in mice kept in constant darkness. This daily pattern of dopaminergic activity may impact upon a variety of temporally regulated retinal events. Moreover, these data will provide a basis for evaluating the role of dopamine in retinal pathology in mouse models of retinal degeneration where mutations affect light perception.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2003

Dietary fatty acids alter blood pressure, behavior and brain membrane composition of hypertensive rats.

The beneficial effect of dietary n-3 polyunsaturated fatty acids (PUFAs) on developing hypertension has been repeatedly demonstrated. However, related changes in brain membrane composition and its cognitive correlates have remained unclear. Our study aimed at a comprehensive analysis of behavior and cerebral fatty acid concentration in hypertension after long-term PUFA-rich dietary treatment. Hypertensive and normotensive rats were provided a placebo, or one of two PUFA-enriched diets with a reduced (n-6)/(n-3) ratio for 75 weeks. Exploratory behavior and spatial learning capacity were tested. Systolic blood pressure (BP) was repeatedly measured. Finally, brain fatty acid composition was analyzed by gas chromatography. Hypertensive rats exhibited more active exploration but impaired spatial learning compared to normotensives. Both diets reduced BP, increased PUFA and monounsaturated fatty acid (MUFA) concentration, and reduced saturated fatty acid content in brain. The level of cerebral PUFAs and MUFAs was lower in hypertensive than in normotensive rats. Furthermore, BP positively, while spatial learning negatively correlated with cerebral (n-6)/(n-3) PUFA ratio. We concluded that regular n-3 PUFA consumption could prevent the development of hypertension, but reached only a very delicate improvement in spatial learning. Furthermore, we consider a potential role of metabolically generated MUFAs in the beneficial effects of PUFA supplementation.

Animals↗
PubMed1990

Using FACS vs. communication scores to measure spontaneous facial expression of emotion in brain-damaged patients: a reply to Mammucari et al. (1988).

Buck and Duffy (1980) and Borod et al. (1985) found evidence of deficits in spontaneous expressiveness in right brain-damaged (RBD) patients relative to LBD patients and controls. Using FACS, Mammucari et al. (1988) failed to replicate this result and questioned our methods and findings. This paper replies (a) that Mammucari et al. (1988)'s review of our work is selective and misleading; (b) that there are aspects of their study that can account for their null results, including the insufficient sensitivity of FACS for the measurement of spontaneous expressiveness; and (c) that the results of Mammucari et al. (1988) regarding "aversive eye movements" to a negative film in LBD and control, but not RBD, patients are in fact compatible with our findings. This paper also suggests a general strategy for the objective and comprehensive analysis of spontaneous emotional expressiveness.

Brain Damage, Chronic↗
PubMed2003

Corneal nerves: structure, contents and function.

This review provides a comprehensive analysis of the structure, neurochemical content, and functions of corneal nerves, with special emphasis on human corneal nerves. A revised interpretation of human corneal nerve architecture is presented based on recent observations obtained by in vivo confocal microscopy (IVCM), immunohistochemistry, and ultrastructural analyses of serial-sectioned human corneas. Current data on the neurotransmitter and neuropeptide contents of corneal nerves are discussed, as are the mechanisms by which corneal neurochemicals and associated neurotrophins modulate corneal physiology, homeostasis and wound healing. The results of recent clinical studies of topically applied neuropeptides and neurotrophins to treat neurotrophic keratitis are reviewed. Recommendations for using IVCM to evaluate corneal nerves in health and disease are presented.

Animals↗
PubMed2003

Assessment of putative protein targets derived from the SARS genome.

The ability to rapidly and reliably develop hypotheses on the function of newly discovered protein sequences requires systematic and comprehensive analysis. Such an analysis, embodied within the DS GeneAtlas pipeline, has been used to critically evaluate the severe acute respiratory syndrome (SARS) genome with the goal of identifying new potential targets for viral therapeutic intervention. This paper discusses several new functional hypotheses on the roles played by the constituent gene products of SARS, and will serve as an example of how such assignments can be developed or extended on other systems of interest.

Amino Acid Sequence↗
PubMed2002

Optimal solution, quantitative performance estimation, and robust tuning of the simplifying controller.

Recently, a simplifying controller has been proposed based on the principal of simplification of the control system transfer functions, which offers improved control for processes with a large time delay. It is the purpose of this complementary paper to give a comprehensive analysis on the scheme. First, the relationship among the simplifying controller, the Smith predictor, and the internal model control are discussed. Second, an analytical design procedure is developed based on internal model control (IMC) and optimal solution is derived. Third, the problem of estimating the time domain performance of the closed loop system, quantitatively, is discussed. Fourth, a simple robust tuning procedure is presented. Numerical examples are provided to illustrate the proposed method.

Computer Simulation↗
PubMed1989

Interplay of hydrophobic and electrostatic interactions in biopolymer chromatography. Effect of salts on the retention of proteins.

The effect of salt on the retention behavior of proteins in electrostatic and hydrophobic interaction chromatography is described by a three-parameter equation, log k' = A - B log ms + Cms, where k' is the retention factor and ms is the molality of the salt in the eluent. Parameter B, termed the electrostatic interaction parameter, depends on the characteristic charge of the protein and the salt counterion and governs the change of retention with the salt concentration in ion-exchange chromatography. According to the model the magnitude of the hydrophobic interaction parameter C is determined by the hydrophobic contact area upon protein binding at the stationary phase surface and the properties of the salt as measured by its molal surface tension increment. Retention data measured at different salt concentrations in the eluent on a variety of ion exchangers can be fitted to the above equation which yields U-shaped plots of log k' against log ms. The limiting slopes of the appropriate plots at sufficiently low and high salt concentrations can be used to evaluate the electrostatic and hydrophobic interaction parameters, respectively. The approach, which is based on a combination of established treatments of electrostatic and hydrophobic interactions offers a convenient framework for analyzing retention data in biopolymer high-performance liquid chromatography and for the characterization of stationary phases. Furthermore, it may facilitate some characterization of protein molecules on the basis of their retention behavior as a function of the concentration and nature of the salt in the eluent. In the treatment of electrostatic interactions use is made of the counterion condensation theory that is believed to make possible a more comprehensive analysis than the traditional stoichiometric ion-exchange model which assumes binding of the proteins by coulombic interactions at discrete sites. The treatment of hydrophobic interactions is based on an adaptation of the solvophobic theory which predicts that the hydrophobic portion of the free energy of binding is proportional to the hydrophobic contact area and the microthermodynamic surface tension of the aqueous salt solution. Despite its simplicity the theory was successful in explaining the observed effect of the nature and concentration of salt in the eluent, the pH and the effect of the density of fixed charges at the surface of the stationary phase in the absence of specific salt effects.

Biopolymers↗
PubMed1997

Mapping of peptides and protein fragments in human urine using liquid chromatography-mass spectrometry.

A method for the mapping of peptide mixtures, heterogeneous with respect to the concentration and the size of individual peptides, was established with the aim of obtaining a comprehensive analysis of human urine peptides. Peptide extraction and fractionation were optimized to achieve a two-step analysis, using reversed-phase and ion-exchange chromatography. Highly sensitive detection of peptides was performed by coupling microbore HPLC with electrospray mass spectrometry (ESI-MS). Peptides such as urodilatin, angiotensin and fragments of psoriasin, granulin and uromodulin were isolated and sequenced. The procedure presented here is a tool for the analysis of complex peptide mixtures from human urine.

Amino Acid Sequence↗
PubMed1998

General method for the detection and in vitro expansion of equine cytolytic T lymphocytes.

Equine immunological research is hindered by the lack of a simple yet reliable general protocol by which to assay CTL activity specific for viral or parasitic antigens. We present here the first comprehensive analysis of the parameters necessary to reliably culture equine T cells and to analyze the antigen specific cytolytic activity of T lymphocytes utilizing the equine infectious anemia virus (EIAV) infection of outbred ponies as a source for in vivo primed T lymphocytes. Effective long-term in vitro culture of equine T cells was determined to require minimally 200 U/ml of recombinant human IL-2. We demonstrated that pokeweed mitogen (PWM) stimulated PBMC generated large quantities of MHC class I and MHC class II expressing autologous lymphoblasts that were used initially to activate and expand antigen specific T lymphocytes and later to serve as a source of target cells in standard chromium release assays. The source of antigen expressed by the PWM lymphoblasts was a recombinant vaccinia virus vector which carried sequences encoding various antigens of interest, but most specifically, the envelope glycoprotein of EIAV. Secondary in vitro stimulation of the T lymphocytes by autologous PWM lymphoblasts expressing EIAV envelope glycoprotein was maximal using a ratio of 10 T cells to one stimulator cell. After antigen stimulation, responding T lymphocytes had antigen specific cytolytic activity and were of both the CD4 and CD8 lineage. The methodology presented here should provide an effective and reliable means by which to analyze the cytolytic activity of equine T lymphocytes to other foreign antigens. Furthermore, we suggest that this method derived for the equine animal model should be applicable to other mammalian and avian model systems that currently lack an effective means by which to analyze antigen specific CTL activity.

Animals↗
PubMed2003

Conformational movements and cooperativity upon amino acid, ATP and tRNA binding in threonyl-tRNA synthetase.

The crystal structures of threonyl-tRNA synthetase (ThrRS) from Staphylococcus aureus, with ATP and an analogue of threonyl adenylate, are described. Together with the previously determined structures of Escherichia coli ThrRS with different substrates, they allow a comprehensive analysis of the effect of binding of all the substrates: threonine, ATP and tRNA. The tRNA, by inserting its acceptor arm between the N-terminal domain and the catalytic domain, causes a large rotation of the former. Within the catalytic domain, four regions surrounding the active site display significant conformational changes upon binding of the different substrates. The binding of threonine induces the movement of as much as 50 consecutive amino acid residues. The binding of ATP triggers a displacement, as large as 8A at some C(alpha) positions, of a strand-loop-strand region of the core beta-sheet. Two other regions move in a cooperative way upon binding of threonine or ATP: the motif 2 loop, which plays an essential role in the first step of the aminoacylation reaction, and the ordering loop, which closes on the active site cavity when the substrates are in place. The tRNA interacts with all four mobile regions, several residues initially bound to threonine or ATP switching to a position in which they can contact the tRNA. Three such conformational switches could be identified, each of them in a different mobile region. The structural analysis suggests that, while the small substrates can bind in any order, they must be in place before productive tRNA binding can occur.

Adenosine Triphosphate↗
PubMed1996

Dental education and practice in the 21st century: opportunities for excellence.

This study describes the environment that can be expected for dental education and dental practice as the 21st century approaches. The study uses data from many sources, including the recent report from the Institute of Medicine, which provides a comprehensive analysis of the variables that will affect dental education and practice in the next decade. Dental education and practice will be able to thrive if the new forces are carefully examined and the challenges are met promptly.

Dental Clinics↗
PubMed2001

Cellular determinants of the mutational specificity of 1-nitroso-6-nitropyrene and 1-nitroso-8-nitropyrene in the lacI gene of Escherichia coli.

We have characterized 202 lacI(-) mutations, and 158 dominant lacI(-d) mutations following treatment of Escherichia coli strains NR6112 and EE125 with 1-nitroso-6-nitropyrene (1,6-NONP), an activated metabolite of the carcinogen 1,6-dinitropyrene. In all, 91% of the induced point mutations occurred at G:C residues. The -(G:C) frameshifts were the dominant mutational class in the lacI(-) collections of both NR6112 and EE125, and in the lacI(-d) collection of NR6112. Frameshift mutations occurred preferentially in runs of guanine residues, and their frequency increased with the length of the reiterated sequence. In strain EE125, which contained the plasmid pKM101, there was a marked stimulation in the frequency of base substitution mutations that was particularly apparent in the lacI(-d) collection. This study completes a comprehensive analysis of 1194 lacI(-) and 348 lacI(-d) mutations induced by either 1,6-NONP or its positional isomer 1-nitroso-8-nitropyrene (1,8-NONP) in strains of E. coli that differ with regard to their ability to carry out nucleotide excision repair and/or their ability to express the translesion synthesis DNA polymerase RI (MucAB) encoded by plasmid pKM101. Among the mutations are 763 frameshift mutations, 367 base substitutions and 47 deletions; these mutations have been characterized at more than 300 distinct sites in the lacI gene. Our studies provide detailed insight into the DNA sequence alterations and mutational mechanisms associated with dinitropyrene mutagenesis. We review the mutational spectra, and discuss cellular lesion repair or tolerance mechanisms that modulate the observed mutational specificity.

Amino Acid Substitution↗
PubMed2000

Functional assessments in mice and rats after focal stroke.

This paper presents a comprehensive assessment of sensorimotor deficits in the mouse after focal ischaemia induced by occlusion of the middle cerebral artery. Twenty four hours after induction of middle cerebral artery occlusion, mice showed deficits in a range of sensory and motor tasks as assessed by the SHIRPA protocol. In addition they exhibited a decrease in rotarod performance and locomotor activity. Some behaviours, such as locomotor activity, were also impaired in sham operated animals compared to normal controls, although these impairments were not as marked as those exhibited by the ischaemic mice. This is the first comprehensive analysis of the short term effects of permanent focal ischaemia in mice. In a second series of experiments in the rat, rates of recovery over time were examined. Simple (neurological grades, rotarod) and complex (sticky label test) tasks were examined in rats after middle cerebral artery occlusion up to 7 days post-ischaemia. Ischaemic rats had a profound deficit in contralateral performance on the sticky label task with no evidence of recovery. A less marked deficit was also observed in ipsilateral performance of this task. These deficits were still present 7 days after ischaemia. Ischaemic rats also exhibited a deficit on rotarod performance but this had recovered 7 days post-ischaemia. Thus different sensorimotor tasks have different rates of recovery after focal cerebral ischaemia in the rat. Further characterisation of these tasks will enhance their utility meaningful preclinical means of assessing functional recovery of the administration of potential neuroprotective and regenerative therapies.

Animals↗
PubMed1995

Curative treatment for pancreatic neoplasms. Radical resection.

The available data suggest that lymph node involvement is an important prognostic factor in patients with carcinoma of the head of the pancreas. Lymph node metastases occur in as many as 50% of the cases of even the smallest pancreatic cancers now being diagnosed and resected (i.e., those < 2 cm in diameter). There is some evidence, especially from clinical experience in Japan, that wider lymphatic dissections (i.e., wider than those commonly done with the standard Whipple resection) may prolong survival. Unfortunately, many of the available data around the world are retrospective and are not randomized between the standard and the radical operation. Moreover, the pathologic material has not been staged uniformly according to accepted criteria. Thus the various series are not comparable. Comparisons between series require standardization with respect to stage of disease, pathologic classification, and treatment protocols. Before any modification of the standard pancreaticoduodenectomy is adopted, an appropriately designed study should be performed to test its efficacy. This study would also require a more comprehensive analysis of the pathologic material than is commonly performed today in the United States and Europe.

Humans↗
PubMed1997

Human herpesvirus-8-associated body cavity-based lymphoma in human immunodeficiency virus-infected patients: a unique B-cell neoplasm.

Human immunodeficiency virus (HIV)-related body cavity-based lymphomas (BCBLs) are known to exhibit unusual clinical, immunophenotypic, and genotypic features, and have recently been found to harbor DNA sequences of a new human herpesvirus, designated Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8). The authors have encountered eight cases of HHV-8-associated BCBL in HIV-infected patients. A literature search revealed an additional 50 reported cases of HIV-related BCBL, as well as reports of several other disorders associated with HHV-8 DNA. Comprehensive analysis of the clinical and pathobiological features of all 58 known cases of HIV-related BCBL shows it to be a unique B-cell neoplasm with a strong propensity for body-cavity involvement without mass lesions and with little or no dissemination, poor prognosis, high grade usually immunoblastic morphology, late B-cell phenotype and genotype, no associated c-myc gene rearrangement, frequent presence of Epstein-Barr virus (EBV) genome, and uniform association with HHV-8 DNA. Considering these features in the context of other disorders associated with HHV-8 DNA, HHV-8 appears to play a causal role in BCBL, possibly in concert with EBV, and may induce this lymphoma through dysregulation of cytokines, particularly interleukin-6, or infection of an unusual B-cell subset. The characteristics of HHV-8-associated BCBL suggest a possible role for antiherpes or anticytokine agents in the treatment of this lymphoma.

DNA, Viral↗
PubMed1999

Altered expression of gamma-glutamyl transpeptidase in human tumors.

Elevated levels of gamma-glutamyl transpeptidase (GGT) activity and intracellular glutathione in tumor cells have been correlated with resistance to several classes of chemotherapeutic drugs. In this study, the first comprehensive analysis of GGT expression in human malignant neoplasms, 451 tumors were immunostained with an antibody directed against a c-terminus peptide of the human GGT protein. Analysis of the immunostaining revealed that GGT was expressed in 22 of 44 lung carcinomas and 16 of 22 ovarian surface epithelial carcinomas, although normal pulmonary and ovarian epithelium are GGT-negative. The tumor samples were obtained from patients before the start of therapy; therefore, GGT was not induced by radiation or chemotherapy. There was no GGT expression in mesotheliomas, Hodgkin's disease, non-Hodgkin's lymphomas, melanomas, basal cell carcinomas, and most soft tissue sarcomas, all of which are derived from GGT-negative cells. Carcinomas arising from some GGT-positive epithelium retained their GGT-positive phenotype. These included renal cell carcinomas, hepatocellular and cholangiocarcinomas, and carcinomas of the prostate and thyroid whereas both pancreatic adenocarcinomas and infiltrating carcinomas of the breast showed a wide range of GGT expression. Further studies are underway to determine whether expression of GGT plays a role in the inherent resistance of some tumors to alkylating agents and other classes of chemotherapeutic drugs.

Female↗