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Biomedical subjects

P Gregor

Publications and source records attributed to P Gregor.

At least 19 recordsLinked to original sources
PubMed1995

Mapping of the taurine transporter gene to mouse chromosome 6 and to the short arm of human chromosome 3.

Transport proteins have essential functions in the uptake of neurotransmitters and neuromodulators. We have mapped the gene encoding the taurine transporter, Taut, to the central region of mouse chromosome 6. Analysis of a cross segregating the neurological mutant mnd2 excluded Taut as a candidate gene for this closely linked mutation. To map the human taurine transporter gene, TAUT, a sequence-tagged site (STS) corresponding to the 3' untranslated region of the human cDNA was developed. TAUT was assigned to human chromosome 3 by typing this STS on a panel of somatic cell hybrids. Further analysis of a hybrid panel containing defined deletions of chromosome 3 suggested that TAUT maps to 3p21-p25. These data extend a conserved linkage group on mouse chromosome 6 and human chromosome 3p. Deletion of TAUT might contribute to some phenotypic features of the 3p- syndrome.

Animals↗
PubMed1995

Pericardial involvement during the course of myocardial infarction. A long-term clinical and echocardiographic study.

STUDY OBJECTIVE: This study investigated the long-term course of infarct-related pericarditis and pericardial effusion. Focus was given to the following issues: incidence and timing of pericarditis and pericardial effusion during the acute phase and 3 years follow-up, size, hemodynamic and clinical consequences of effusions, and potential risk of thrombolytic or anticoagulant therapy in patients with pericardial effusion. PATIENTS AND STUDY DESIGN: Serial echocardiographic examinations were performed in 192 consecutive patients with first myocardial infarction during the acute phase (day 1, 5, 10, 21) and during 3 years' follow-up (year 1, 2, and 3 after infarction). The follow-up was 100%. Clinical, angiographic, and autopsy data were analyzed. RESULTS: Pericardial effusion was detected at least once during serial echocardiographic examinations in 82 of 192 patients (43%). The incidence in different subgroups (with or without thrombolysis, open or closed artery at 3 weeks, infarction in left anterior descending, left circumflex, or right coronary artery perfusion bed) was similar. Most (48%) effusions were first detected on the fifth day, and most (50%) disappeared between days 21 and 365. However, in nine patients, the effusion persisted beyond 1 year (up to 3 years in three patients). Only systolic separation of pericardial layers was detected in 59% of effusions, circular effusion in 3.6% of all effusions. No cardiac tamponade developed. Heart failure or death complicated 49% of infarctions with pericardial involvement and 16% of infarctions without effusion (p < 0.01). Mortality alone was 8% among patients without effusion and 15% among those with more than minimal effusion (not significant). CONCLUSIONS: Pericardial effusion can be detected by serial echocardiographic examinations in 43% of myocardial infarctions. It appears during the initial 5 days and disappears slowly during several weeks to several months. Anticoagulant and thrombolytic therapy does not increase the frequency or the size of effusions.

Adult↗
PubMed1994

Clonal variants of hybridoma cells that switch isotype at a high frequency.

As B cells differentiate under the influence of antigen and T cells, they frequently switch from the expression of IgM antibody to the expression of other isotypes. This is accomplished by rearranging the expressed variable region gene to downstream constant region genes and deleting the intervening sequences. Some B-cell lines that represent early stages in development switch constitutively in culture at frequencies that approach those of lipopolysaccharide- or lymphokine-stimulated normal B cells. Hybridoma cells represent a later stage of development and rarely switch in culture. In contrast to early B-cell lines, hybridomas produce large amounts of immunoglobulin, and single cells can be assayed easily for the expression of new isotypes. We have used the ELISA spot assay and fluctuation analysis to determine the rate of switching of two hybridoma cell lines. By identifying subclones that switched more frequently, we have progressively enriched for cells that switch spontaneously at higher rates. These cells, like normal cells, switch by rearrangement and deletion, and the frequency of switched cells in some of the clones is comparable to that which has been observed in less differentiated B-cell lines and in normal B cells.

Animals↗
PubMed1994

Genetic and physical mapping of the GLUR5 glutamate receptor gene on human chromosome 21.

Glutamate receptors (GluRs) mediate excitatory neurotransmission and may have important roles in central nervous system disorders. To characterize the human GLUR5 gene, which is located on human chromosome 21q22.1, we isolated cDNAs, genomic phage lambda clones, and yeast artificial chromosomes (YACs) and developed sequence tagged sites (STSs) and simple sequence length polymorphisms (SSLPs) for GLUR5. Genetic mapping with a tetranucleotide AGAT repeat named GLUR5/AGAT (six alleles observed, 70% heterozygosity) placed GLUR5 5 cM telomeric to APP (D21S210) and 3 cM centromeric to SOD1 (D21S223). The human GLUR5 gene is located near the familial amyotrophic lateral sclerosis (FALS) locus; linkage analysis of GLUR5 SSLPs in FALS pedigrees yielded negative lod scores, consistent with the recent association of the FALS locus with the SOD1 gene. Physical mapping of GLUR5 using a YAC contig suggested that the GLUR5 gene spans approximately 400-500kb, and is within 280kb of D21S213. The large size of the GLUR5 gene raises questions regarding its functional significance. Our GLUR5 YAC contig includes clones found in the Genethon chromosome 21 YAC contig, and reference to the larger contig indicates the orientation centromere--D21S213-GLUR5 5' end-GLUR5/AGAT--GLUR5 3' end--SOD1. The development of GLUR5/AGAT should permit rapid determination of the status of the GLUR5 gene in individuals with partial trisomy or monosomy of chromosome 21. Such studies may provide insights concerning the possible role of GLUR5 in Down syndrome.

Base Sequence↗
PubMed1994

Schizophrenia and glutamate receptor genes.

Nine multiplex schizophrenia families were genotyped with polymorphisms for the GLUR5 and NMDAR1 glutamate receptor subunit genes. Using the lod score technique, evidence of linkage was not found assuming either dominant or recessive transmission. Similarly, the non-parametric sib pair test did not yield significant evidence of linkage.

Genetic Linkage↗
PubMed1994

Cloning, pharmacological characterization, and genomic localization of the human creatine transporter.

The complete coding sequence from a human creatine transporter cDNA was isolated from a kidney library. This transporter is a member of a superfamily of proteins which includes the family of Na(+)- and Cl(-)-dependent transporters responsible for the uptake of certain neurotransmitters (e.g. dopamine, GABA, serotonin, and norepinephrine), and amino acids (e.g. glycine). Within this family, the human creatine transporter is strongly related to a subfamily of sequences which includes the transporters for taurine, GABA, and betaine, and this cDNA is approximately 98% amino acid identical to sequences that have been reported from rat and rabbit as choline and creatine transporters respectively. Pharmacological characterization demonstrated that the protein product of this cDNA mediated high affinity (Km = 77 +/- 6 microM) creatine uptake, which was blocked by creatine analogs with high affinity. There was no specific transport of choline. Northern analysis demonstrated highest levels of mRNA expression in human skeletal muscle, kidney, and heart, with lower levels in brain and other tissues. Expression within the kidney was evenly distributed between cortex and medulla. Genetic mapping in the mouse localizes the creatine transporter to a region on the X chromosome in linkage conservation with the human region Xq28, the location of the genes for several neuromuscular diseases.

Amino Acid Sequence↗
PubMed1993

mu opiate receptor: cDNA cloning and expression.

mu opiate receptors recognize morphine with high affinity. A 2.1-kb rat brain cDNA whose predicted translation product displays 63% identity with recently described delta and kappa opiate receptor sequences was identified through polymerase chain reaction and cDNA homology approaches. This cDNA recognizes a 10.5-kb mRNA that is expressed in thalamic neurons. COS-cell expression confers naloxonazine-, Na(+)-, and GTP-sensitive binding of mu but not delta or kappa opioid ligands. Expressing cells bind morphine, [D-Ala2,N-methyl-Phe4,glyol5]enkephalin (DAMGO), and [D-Ala2,D-Leu5]enkephalin (DADLE) with nanomolar or subnanomolar affinities, defining a mu opiate receptor that avidly recognizes analgesic and euphoric opiate drugs and opioid peptides.

Amino Acid Sequence↗
PubMed1993

Expression and novel subunit isoforms of glutamate receptor genes GluR5 and GluR6.

Molecular heterogeneity of kainate-selective glutamate receptor subunits GluR5 and GluR6 was revealed by identification of a human cDNA, GluR5-1d, and a murine cDNA, GluR6-2, that each encode subunits with novel carboxy-terminal sequences. Both GluR5-1d and GluR6-2 appear to be generated by alternative splicing at analogous sites 14 codons following the fourth putative transmembrane segment. The principal transcripts of GluR5 and GluR6 were detected by Northern analyses of several regions of mammalian brains as 4 and 6 kb bands, respectively. Potential roles for these receptors in development are indicated by detection of their mRNAs in mouse embryos of 11 days gestation. These findings add to the description of the remarkable diversity of glutamate receptor gene expression.

Amino Acid Sequence↗
PubMed1993

Chromosomal localization of glutamate receptor genes: relationship to familial amyotrophic lateral sclerosis and other neurological disorders of mice and humans.

Receptors for the major excitatory neurotransmitter glutamate may play key roles in neurodegeneration. The mouse Glur-5 gene maps to chromosome 16 between App and Sod-1. The homologous human GLUR5 gene maps to the corresponding region of human chromosome 21, which contains the locus for familial amyotrophic lateral sclerosis. This location, and other features, render GLUR5 a possible candidate gene for familial amyotrophic lateral sclerosis. In addition, dosage imbalance of GLUR5 may have a role in the trisomy 21 (Down syndrome). Further characterization of the murine glutamate receptor family includes mapping of Glur-1 to the same region as neurological mutants spasmodic, shaker-2, tipsy, and vibrator on chromosome 11; Glur-2 near spastic on chromosome 3; Glur-6 near waltzer and Jackson circler on chromosome 10; and Glur-7 near clasper on chromosome 4.

Amyotrophic Lateral Sclerosis↗
PubMed1993

Recent atrial fibrillation in acute myocardial infarction: a sign of pericarditis.

The association between recent atrial fibrillation during the course of acute myocardial infarction and pericarditis or pericardial effusion occurring during the hospital phase of myocardial infarction was studied by means of serial echocardiographic examinations in 192 patients presenting with their first myocardial infarction. Clinical pericarditis was found in 8%, echocardiographic effusion in 43%, and atrial fibrillation in 5% of all patients. Atrial fibrillation was present in only 2% of patients without pericardial effusion compared to 15% of patients with more than minimal effusion (p = 0.0094). Thus, pericarditis might play a role in the development of recent atrial fibrillation during the course of myocardial infarction. Recent atrial fibrillation may be a sign of pericardial effusion which may be otherwise silent.

Atrial Fibrillation↗
PubMed1993

The course of myocardial hypertrophy in hypertrophic cardiomyopathy. Results of a 10-year follow-up.

Sixty-nine patients with hypertrophic cardiomyopathy were followed up for a minimum period of 10 years, with detailed quantitation of myocardial hypertrophy using two-dimensional echocardiography at a two-year interval. The parameters determined included maximum myocardial wall thickness, mean myocardial wall thickness (defined as the arithmetic mean of myocardial wall thickness values measured in ten areas of approximately the same size the LV and septal myocardium had been divided into), and the extent of hypertrophy (percentage of the myocardium affected by hypertrophy). Other echocardiographic parameters as well as clinical, ECG and Holter data were also assessed. Seven patients (10%) showed a gradual increase in mean myocardial wall thickness (associated with an increase in maximum myocardial wall thickness and in the extent of hypertrophy in two). By contrast, a progressive decrease in hypertrophy was observed in six patients (9%). In either case, the observed changes tended to involve areas in segments outside the zone of maximum wall thickness. Generally, the changes in hypertrophy were not related to the development of clinical or Holter manifestations, and were unaffected by verapamil or beta-blocker therapy. There was no death among these patients unlike the five deaths in a group with stationary hypertrophy. Based on their results, the authors conclude that changes in myocardial hypertrophy (regardless of whether there is progression or regression) probably make part of natural variations in the course of the disease, and have no clinical or prognostic implications for the majority of patients.

Adult↗
PubMed1993

[The optimal diagnostic approach in myocardial infarct].

In the submitted review the authors discuss rational criteria for the diagnosis of myocardial infarction, indications for thrombolysis, coronarography and possibly PTCA, the method of indirect (non-invasive) assessment of an occluded coronary artery and the most frequent mistakes in the diagnosis of infarction. Essential examinations in the acute stage of myocardial infarction are: case-history, ECG, CK-MB (possibly echocardiography). For indication of thrombolysis of acute PTCA case-history and ECG (or echocardiography) are sufficient. Indications of early coronarography before discharge from hospital: postinfarction angina pectoris, malignant arrhythmia (except on the first day), haemodynamic instability, evidence of myocardial ischaemia (restricted symptoms) during a maximal load before discharge.

Humans↗
PubMed1992

Cloning of an apparent splice variant of the rat N-methyl-D-aspartate receptor NMDAR1 with altered sensitivity to polyamines and activators of protein kinase C.

Molecular cloning identified complementary DNA species, from a rat ventral midbrain library, encoding apparent splice variants of the N-methyl-D-aspartate (NMDA) receptor NMDAR1 (which we now term NR1a). Sequencing revealed that one variant, NR1b, differs from NR1a by the presence of a 21-amino acid insert near the amino end of the N-terminal domain and by an alternate C-terminal domain in which the last 75 amino acids are replaced by an unrelated sequence of 22 amino acids. NR1b is virtually identical to NR1a in the remainder of the N- and C-terminal domains, at the 5' and 3' noncoding ends, and within the predicted transmembrane domains and extracellular and cytoplasmic loops. These findings suggest that the two forms of the receptor arise by differential splicing of a transcript from the same gene. Sequencing of other clones indicates the existence of a third variant, NR1c, identical to NR1b in its C terminus but lacking the N-terminal insert. NR1b RNA injected into Xenopus oocytes generated functional homomeric NMDA channels with electrophysiological properties distinct from those of NR1a homomeric channels. NR1b channels exhibited a lower apparent affinity for NMDA and for glutamate. NR1b channels exhibited a lower affinity for D-2-amino-5-phosphonovaleric acid and a higher affinity for Zn2+. The two receptor variants showed nearly identical affinities for glycine, Mg2+, and phencyclidine. Spermine potentiation of NMDA responses, prominent in oocytes injected with rat forebrain message, was also prominent for NR1a receptors, but was greatly reduced or absent for NR1b receptors. Treatment with the protein kinase C activator phorbol 12-myristate 13-acetate potentiated NMDA responses in NR1b-injected oocytes by about 20-fold; potentiation of NMDA responses in NR1a-injected oocytes was much less, about 4-fold. These findings support a role for alternate splicing in generating NMDA channels with different functional properties.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1992

Organization and expression of the gene encoding chick kainate binding protein, a member of the glutamate receptor family.

The gene encoding chick cerebellar Bergmann glia-specific kainate binding protein (chKBP), has been isolated, characterized and expressed in heterologous systems. The structural gene spans 11.2 kb and contains 11 exons and 10 introns. Several of the exons encode specific receptor domains, including each of the predicted transmembrane regions. Exon/intron boundaries flanking the second, putative channel-forming transmembrane domain are conserved between chKBP and other glutamate/kainate receptor subunits. The putative promoter region 5' to the first exon displays high GC content and TATA, CAAT and AP1 consensus sequences. Transcription of the chKBP gene is evident prior to full cerebellar cortical maturation. Transcripts are abundant in cells consistent with Bergmann glia, as revealed by in situ hybridization. Transfection of 293 kidney cell cultures with chKBP cDNA or chKBP gene expression constructs confers CNQX-sensitive kainate binding with the pharmacological specificity displayed by both chKBP and kainate receptors. However, expression of the same constructs in Xenopus oocytes fails to yield detectable agonist-activated currents.

Amino Acid Sequence↗