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PubMedDate not supplied

Duplicated plastid and triplicated cytosolic isozymes of triosephosphate isomerase in maize (Zea mays L.).

We studied electrophoretic variation and inheritance of triosephosphate isomerase (TPI) isozymes in maize (Zea mays L.). In contrast to most diploid plants, in maize, TPI exists as multiple isozymes in both the plastid and cytosolic subcellular compartments. Phenotypes result from the overlay of two independent sets of isozymes and allozymes, representing the plastid (encoded by the nuclear genes Tpi1 and Tpi2) and cytosolic (encoded by Tpi3, Tpi4, and Tpi5) systems. All possible intragenic and intergenic dimeric enzymes are formed between polypeptides within each subcellular compartment. No heterodimers are formed between plastid and cytosolic polypeptides. Extensive surveys of accessions of land races and inbred lines revealed 22 allelic variants for the five loci. Most alleles have been formally validated by segregation analysis. We describe two null alleles at Tpi4, distinguished by their relative abilities to form intergenic heterodimers with polypeptides specified by Tpi3 and Tpi5. Linkage analyses and crosses with B-A translocation stocks were effective in determining the chromosome locations of all five loci. Duplicated genes for both the plastid and cytosolic isozymes were localized to genomic regions that possess numerous other redundant sequences. We placed Tpi1 on the long arm of chromosome 7, approximately 23 centimorgans (cM) distal to g11; we localized its duplicate--Tpi2--17 cM distal to v4 on the long arm of chromosome 2. The triplicate loci encoding cytosolic TPIs reside on chromosomes 3 and 8. Tpi4 is approximately equidistant (11 cM) from d1 and Lg3, near the centromere of chromosome 3. Tpi3 and Tpi5 are located on distal ends of the most poorly marked maize chromosome; Tpi3 is 29 cM distal to Idh 1 on 8L, and Tpi5 is on 8S or near the centromere on 8L. In contrast to most duplicated maize sequences, which often occur in parallel linkages on different chromosomes, Tpi3 and Tpi5 provide an example of intrachromosomal gene duplication. Several of the Tpi loci are located in sparsely mapped regions of the genome, and Tpi1 is the first isozyme marker for chromosome 7.

Alleles↗
PubMed2002

Ras processing as a therapeutic target in hematologic malignancies.

Knowledge of signal transduction pathways has uncovered therapeutic targets for cancer. Based on genetic and biochemical studies of leukemia cells, inhibiting hyperactive Ras represents a rational therapeutic strategy for many hematologic malignancies. Because posttranslational processing by farnesyltransferase is essential for transformation by oncogenic Ras, specific inhibitors of this enzyme are being evaluated as cancer therapeutics. The authors review recent laboratory insights on farnesyltransferase biology and on the development of inhibitors, summarize preclinical and clinical data in myeloid malignancies, and briefly discuss other strategies of interfering with hyperactive Ras.

Alkyl and Aryl Transferases↗
PubMed1985

Further studies on bivalent chiasma frequency in human males with normal karyotypes.

Previously unpublished data on the chiasma frequency of individual bivalents identified by a triple staining technique are presented for four males. The total autosomal cell chiasma frequency and sex chromosome univalence frequency are also given for these males and for three others. All seven males had apparently normal 46,XY karyotypes and normal spermatogenesis. The extent of inter-individual variation in cell and bivalent chiasma frequency and the gross relationship between chromosome length and chiasma frequency are discussed.

Adult↗
PubMed1987

The locus ordering problem.

Studies of phenotypes defined by codominant alleles at two or more loci in three-generation families allow haplotypes to be deduced. These data are easily summarized by the Mendelian convention of upper and lower case, with case defining phase rather than nature. In two-generation families haplotypes may be inferred with high precision for closely linked loci even if an allele at one locus is recessive. Coding procedures are discussed and a simple solution to inferring the most likely order of three or more loci, and defining its likelihood compared with other orders, is presented.

Chromosome Mapping↗
PubMed1996

Clinical significance of a new P wave lead vector for pacemaker follow-up of atrial functions.

Patient welfare requires routine follow-up procedures of implantable pacemakers. However, the assessment of atrial sensing and pacing functions in implantable pacemakers is often a challenge due to difficult identification of low amplitude P waves on surface electrocardiograms (ECGs). A previous body surface mapping study suggested that a novel P wave lead vector (P lead) had larger root mean square values than other standard leads. However, for pacemaker follow-up procedures, peak-to-peak amplitudes are more relevant than root mean square values. In this study, the peak-to-peak amplitudes of intrinsic and paced P waves recorded from surface ECG standard lead II and the P lead were compared. In addition, intrinsic and paced R waves were also compared. Data recorded from 15 patients undergoing electrophysiological studies indicated that peak-to-peak amplitudes of the P lead were significantly larger than standard lead II: 24% for intrinsic P waves, 30% for paced P waves, and 72% for intrinsic R waves. In addition, the P lead amplitude of paced R waves showed a nonsignificant increase of 24% compared with standard lead II. Therefore, the use of this new lead vector may improve the clinical ease-of-use and reduce the time required for follow-up procedures of implantable pacemakers for atrial sensing and pacing assessments.

Atrial Function↗
PubMed1992

Direct extraction of bacterial plasmids from food for polymerase chain reaction amplification.

In this report we describe a simple and rapid technique using DNA affinity columns that permits direct extraction of bacterial plasmids from a variety of foods for polymerase chain reaction amplification. The procedure was used to detect virulent enteroinvasive Escherichia coli in several artificially seeded matrices, including seafoods, greens, dairy products, enrichment media, and water. Polymerase inhibitors present in both foods and enrichment media were removed efficiently.

DNA, Bacterial↗
PubMed1994

Phenotypic variation of tuberous sclerosis in a single extended kindred.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with a great degree of phenotypic variability. Given the presence of two gene loci underlying this disorder, locus heterogeneity may account for some of the variability. However, significant within family variation suggests that different genes do not explain the majority of this variation. The purpose of this research is to identify physical and behavioural variation in expression of TSC in a single large extended kindred. TSC in this kindred is cosegregating with markers localised to chromosome 16p13.3. The expression of TSC in this kindred is quite variable with a substantial proportion of persons showing very mild physical expression of TSC. In contrast to very mild physical expression of TSC in some family members, there is a significant clustering of psychiatric disorders among persons affected with TSC compared to their unaffected relatives. This finding, coupled with the mild physical expression of TSC in some family members, supports a hypothesis that the TSC2 gene may present phenotypically as mild skin signs and significant behavioural problems.

Adolescent↗
PubMed2005

Discovery of highly differentiative gene groups from microarray gene expression data using the gene club approach.

MOTIVATION: It is commonly believed that suitable analysis of microarray gene expression profile data can lead to better understanding of diseases, and better ways to diagnose and treat diseases. To achieve those goals, it is of interest to discover the gene interaction networks, and perhaps even pathways, underlying given diseases from such data. In this paper, we consider methods for efficiently discovering highly differentiative gene groups (HDGG), which may provide insights on gene interaction networks. HDGGs are groups of genes which completely or nearly completely characterize the diseased or normal tissues. Discovering HDGGs is challenging, due to the high dimensionality of the data. RESULTS: Our methods are based on the novel concept of gene clubs. A gene club consists of a set of genes having high potential to be interactive with each other. The methods can (i) efficiently discover signature HDGGs which completely characterize the diseased and the normal tissues respectively, (ii) find strongest or near strongest HDGGs containing any given gene, and (iii) find much stronger HDGGs than previous methods. As part of the experimental evaluation, the methods are applied to colon, prostate, ovarian, and breast cancer, and leukemia and so on. Some of the genes in the extracted signature HDGGs have known biological functions, and some have attracted little attention in biology and medicine. We hope that appropriate study on them can lead to medical breakthroughs. Some HDGGs for colon and prostate cancers are listed here. The website listed below contains HDGGs for the other cancers. AVAILABILITY: HDGG is implemented in C++ and runs on Unix or Windows platform. The code is available at: http://www.cs.wright.edu/~gdong/hdgg/.

Algorithms↗
PubMed1986

Neurons of C1 area mediate cardiovascular responses initiated from ventral medullary surface.

We sought to establish whether neurons of the C1 area of the rostral ventrolateral medulla (RVL) mediate changes in arterial pressure and heart rate evoked by topical application of drugs to the ventral medullary surface of the rat. Animals were anesthetized, paralyzed, and ventilated. The ventral surface was mapped with L-glutamate, and a restricted zone was identified from which L-glutamate, as well as kainic acid, bicuculline, strychnine, carbachol, or physostigmine, increased arterial pressure and heart rate. The hypertensive effects of carbachol and physostigmine were blocked by previous local application of atropine but not hexamethonium. Application of gamma-aminobutyric acid (GABA) or glycine to this area produced hypotension and bradycardia. Located caudal to the trapezoid bodies and lateral to the pyramids, this area corresponded to points with lowest threshold for pressor responses evoked by electrical stimulation and overlapped the distribution of epinephrine-synthesizing cells of the RVL. Processes arising from these neurons were identified reaching and contacting the ventral surface. Unilateral lesions involving the C1 area or phenylethanolamine-N-methyltransferase-labeled descending axons derived from this area imparied by greater than 70% the response to ipsilateral application of L-glutamate, GABA, or glycine to the ventral surface. We suggest that neurons within the C1 area of RVL adjacent to or including epinephrine cells may mediate cardiovascular changes elicited from a restricted chemosensitive zone of the ventral medullary surface of the rat.

Animals↗
PubMed2004

Topical treatment with inhibitors of the phosphatidylinositol 3'-kinase/Akt and Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways reduces melanoma development in severe combined immunodeficient mice.

Topical treatment with inhibitors of the phosphatidylinositol 3'-kinase/Akt and Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways inhibited the growth of TPras transgenic melanomas in severe combined immunodeficient mice, blocked invasive behavior, and reduced angiogenesis. The inhibitor Ly294002, which is specific for phosphatidylinositol 3'-kinase, effectively reduced melanoma cell growth both in vitro and in vivo. Both Ly294002 and U0126, a mitogen-activated protein kinase kinase 1/2 inhibitor, reduced invasion, which correlated with reduction of the metalloproteinase matrix metalloproteinase 2. Tumor angiogenesis was disrupted through inhibition of vascular endothelial growth factor production from the tumor cells and antiangiogenic effects on endothelial cells. Observations with TPras melanoma cells that express dominant negative Deltap85 or kinase-inactive Raf(301) supported the specificity of the phenomena observed with the chemical inhibitors. These studies demonstrate that topical treatment targeting Ras effectors is efficacious, without systemic toxicities, and may prove to be useful in treating and preventing the progression of cutaneous melanoma.

Administration, Topical↗
PubMed1999

cDNA cloning, characterization and chromosome mapping of the gene encoding human cartilage associated protein (CRTAP).

We have recently isolated and characterized cDNA clones coding for a novel developmentally regulated avian and mouse embryo protein, CASP for Cartilage Associated Protein. Here we describe the isolation and characterization of the gene coding for the human CASP. The comparison of the putative human and mouse protein sequences with the chick sequence revealed an overall high identity (89% and 51%, respectively). Homology search with known DNA and protein sequences showed that CASPs are related to two mammalian nuclear proteins. Here we demonstrate definitively that CASPs are distinct from these nuclear proteins. However, sequence comparison analyses suggest that all of these proteins belong to a new family. In all human tissues examined two CASP mRNA species were detected, whereas a single mRNA and three mRNAs were found in chick and mouse, respectively. The human CASP gene (CRTAP) was assigned to chromosome 3p22 by fluorescence in situ hybridization.

Amino Acid Sequence↗
PubMedDate not supplied

Mapping in the sequencing era.

The present phase of the Human Genome Project is concerned with sequencing. The shift of emphasis has left an impression that mapping is in some sense complete or finished. On the contrary, faced with the challenges of mapping genes for complex traits and efforts to understand recombination and other biological processes, the need for accurate integrated metric maps is greater than ever. Furthermore, sequencing could be regarded as merely a way of improving the map, since the most useful 'end product' of the sequencing effort must be the annotated sequence that gives precise physical coordinates for markers and expressed sequences. Integration of both location and functional information, the latter provided by homology, expression and other functional studies, is the main target for the future.

Chromosome Mapping↗
PubMed1999

Do microelectrode techniques increase accuracy or decrease risks in pallidotomy and deep brain stimulation? A critical review of the literature.

Several recent publications have stated that the use of microelectrode recording (MER) during pallidotomy or deep brain stimulation (DBS) contributes to decreasing risks and side effects of surgery, and that such a technique is a prerequisite for minimizing lesion size and for accurate placement of the stereotactic lesion or the DBS electrode. To evaluate the consistency of these statements, we reviewed hundreds of papers and congress reports on MER- and non-MER-guided procedures published since 1992. This review showed that MER groups published more often than non-MER groups. While side effects of surgery were not uncommon in both groups, the rate of severe complications, such as hematoma, and mortality appeared to be higher when microelectrodes were used, both in ablative surgery and in DBS procedures. Besides, the nonaccurate placement of lesions or DBS electrodes, as assessed on published MRI figures, was not uncommon in MER publications. Lesion volume was, when reported, not different in both techniques. The electrical parameters of stimulation of implanted electrodes in the thalamic ventral intermediate (Vim) nucleus for treatment of tremor were higher in MER-guided surgery. The available literature suggests that MER techniques may increase the risks of surgery without enhancing its accuracy, compared to MRI-based macrostimulation techniques. To date, there is no randomized trial by one and the same group on the use of micro- versus macroelectrodes in surgery for movement disorders. A prerequisite for such a trial in the future must imply that the investigators have an equal nonprejudiced attitude towards, and equal confidence and experience in, either technique. Since such a prerequisite does not exist so far in the functional stereotactic community, a critical and comparative study of the available literature remains the only way to evaluate the pros and cons of either technique, in terms of targeting accuracy and surgical complications.

Bibliometrics↗