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Biomedical subjects

P Gregor

Publications and source records attributed to P Gregor.

At least 19 recordsLinked to original sources
PubMed1998

[Angiotensin-converting enzyme inhibitors. Familiar drugs--new indications].

Angiotensin converting enzyme inhibitors (ACE) have become an important part in the pharmacotherapy of hypertension, in this indication they were used for the first time in the eighties. Later the indication was extended to heart failure (where they evidently reduce the mortality), acute myocardial infarction (there they prevent cardiac remodelling), and in myocarditis (vasodilatation, effect on spasms and on free oxygen radicals). As to non-cardiological indications the most important indications are nephrological-diabetic and non-diabetic nephropathies. Nowadays already different types of ACE inhibitors are available. They differ as to their chemical structure (they contain a sulphydryl or carboxyl group in the molecule, they are proline derivatives etc.) as well as by other properties (lipophilia, specificity, absorption rate, period of action). The authors gives a list of preparations encountered most frequently on our market and they discuss non obvious indications.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Cloning and expression of the human galanin receptor GalR2.

Galanin is a peptide hormone which modulates a wide variety of physiological processes, including secretion, muscle contraction, cognitive function, the reproductive axis, and feeding. Two galanin receptor subtypes, GalR1 and GalR2, have been cloned; however, for GalR2 only the rat sequence has been reported in the literature. Our cloning of human GalR2 reveals its amino acid sequence to be 85% identical to rat GalR2 and 39% identical to human GalR1. Binding of [125I]galanin to the human GalR2 receptor transiently expressed in COS-7 cells was saturable (Kd = 0.24 nM +/- 0.06 nM) with a receptor density of 383 +/- 66 fmol/mg protein. Human galanin(1-30) bound with high affinity to the human GalR2 receptor, with a Ki value of 0.86 +/- 0.12 nM. With the identification of a second galanin receptor subtype, the specific functions of human galanin receptor subtypes can now begin to be addressed.

Amino Acid Sequence↗
PubMed1997

Cloning of a novel member of the G protein-coupled receptor family related to peptide receptors.

We have used PCR with degenerate oligonucleotide primers to clone novel members of the G protein-coupled receptor (GPCR) superfamily. We report here a novel gene, CEPR, which encodes a candidate receptor that is most similar to the peptide receptor family. The coding region of the human CEPR gene predicts a seven transmembrane domain (TM) receptor of 375 amino acids. CEPR has 28-30 percent amino acid identity to angiotensin II and interleukin 8 receptors, and slightly lower percent identity to many other GPCRs. Northern blot analysis reveals a 3.3 kb CEPR transcript in different regions of human brain and in various peripheral tissues. The ubiquitous tissue distribution of CEPR, its expression in early development, and its conservation in evolution indicate a potentially important biological function for this receptor and its putative peptide ligand.

Amino Acid Sequence↗
PubMed1997

Nebivolol in the treatment of cardiac failure: a double-blind controlled clinical trial.

BACKGROUND: Nebivolol is a highly cardioselective long-acting beta-blocker with vasodilating properties, which acts in part via the endothelial L-arginine/nitric oxide pathway. As an antihypertensive drug it is effective in once-daily dosage. Nebivolol has previously been shown to improve left ventricular function in patients with cardiac impairment. METHODS AND RESULTS: This paper reports a double-blind randomized trial comparing, in patients with heart failure, once-daily nebivolol 2.5 or 5.0 mg (initiated in all at 2.5 mg) with placebo on a constant background of digitalis plus diuretic. There was with nebivolol no overall deterioration of cardiac function or cardiac symptoms, and especially not of exercise capacity, in comparison with placebo. One patient on nebivolol 2.5 mg developed hypotension and pulmonary edema, and one patient on nebivolol 5 mg, bradycardia. All the remaining patients continued with unchanged diuretic and digitalis dosage. Nebivolol was accompanied by a trend toward clinical and functional improvement; rather better results were obtained with 2.5 than 5.0 mg. CONCLUSIONS: In view of increasing interest in beta-blockade in heart failure, nebivolol merits further study in this context. The capacity of nebivolol to enhance endothelial nitric oxide production appears potentially attractive.

Adrenergic beta-Antagonists↗
PubMed1997

Detection of malignant and benign breast lesions with an automated US system: results in 120 cases.

PURPOSE: To evaluate clinically an automated ultrasound (US) system for detecting benign and malignant breast lesions. MATERIALS AND METHODS: A prototype automated US system was used to examine 119 patients: 38 patients with 39 proved malignant breast lesions (7-50 mm), 41 patients with 41 proved benign breast lesions (8-40 mm), and 40 patients without breast lesions. The device yields a three-dimensional set of B-mode scans and reconstructed US images comparable to mammograms. All patients had undergone mammography. Four radiologists who had not performed the examinations independently assessed the mammograms and US images to detect benign and malignant breast lesions. RESULTS: Each of the four readers did not recognize one to three detectable malignant lesions on mammograms, one to two detectable malignant lesions on US images, two to four detectable benign lesions on mammograms, and five to seven detectable benign lesions on US images. All readers identified the 39 cancers with at least one of the modalities. The 40 cases without lesions were diagnosed correctly more frequently on the US images by three readers and on the mammograms by one reader. CONCLUSION: Depiction of breast lesions at automated US is reproducible. Automated US is complementary to mammography.

Breast Diseases↗
PubMed1997

Ventricular arrhythmias in myocardial hypertrophy of various origins.

It has not been explained whether the etiological substrate of left ventricular hypertrophy has any influence on prevalence and severity of ventricular arrhythmias. Therefore, 48 h ambulatory electrocardiographic monitoring findings were compared in two groups of untreated patients without coronary artery disease and with no significant differences in age, sex, maximal and average myocardial thickness and left ventricular systolic function. Group A comprised 42 patients with pressure overload hypertrophy due to essential hypertension, and group B comprised 42 patients with hypertrophic cardiomyopathy. The prevalence of complex ventricular arrhythmias (Lown 3a-4b) was high in both groups (65% versus 60%, respectively, not significant). No significant difference was found in total frequency of most serious arrhythmias: Lown 4a, 26 versus 21 events (not significant), and Lown 4b, 20 versus 28 events (not significant). There was a correlation between prevalence of complex ventricular arrhythmias and maximal myocardial thickness in both groups of patients (P < 0.05), and, in group A only, between prevalence of complex ventricular arrhythmias and age (P < 0.01). It was concluded that, although the etiology of pressure overload hypertrophy of the left ventricle and that of hypertrophic cardiomyopathy are completely different, the overall prevalence and spectrum of ventricular arrhythmias in both types of hypertrophy are identical.

Adult↗
PubMed1996

Molecular characterization of a second mouse pancreatic polypeptide receptor and its inactivated human homologue.

The family of mammalian neuropeptide Y (NPY)/peptide YY (PYY)/pancreatic polypeptide (PP) receptors comprises several G protein-coupled receptors, i.e. Y1, Y2, and Y4/PP1. We now report cloning of a novel member of this family named PP2. The coding region of the mouse PP2 gene reveals no introns and predicts a seven transmembrane domain (TM) receptor of 371 amino acids. Percent identities of the mouse PP2 to mouse Y1, mouse Y4/PP1 and human Y2 receptors are 53, 42, and 31, respectively. The mouse PP2 receptor expressed in COS cells binds rat 125I-PP with high affinity, i.e. IC50 = 65 pM. Pharmacological characterization of 125I-PP binding shows a rank order of potency of PP >> PYY >/= NPY, which is similar to that of the mouse Y4/PP1 receptor. Mouse PP2 transcripts were not detectable by Northern analysis in adult tissues and in 11-, 15-, and 17-day-old embryos. However, a 9.8-kb PP2 transcript was detectable in 7-day-old mouse embryo, i.e. prior to the organogenesis of pancreas and the onset of PP production. We have also cloned the human homologue of PP2, which is a single copy gene and maps to human chromosome 5q31. Surprisingly, the human PP2 cDNAs and gene sequences display a single base deletion in the coding region. This frameshifting mutation predicts a truncated receptor of 290 amino acids without TM7. Transfection of COS-7 cells with several different human PP2 expression constructs failed to confirm any specific binding of 125I-PP, 125I-PYY, or 125I-NPY to cell membranes. These data suggest that in mouse there are at least two PP receptors, Y4/PP1 and PP2, whereas in humans, PP2 is either functionally inactive or it has acquired a PP-independent function.

Amino Acid Sequence↗
PubMed1996

Cloning and characterization of a novel receptor to pancreatic polypeptide, a member of the neuropeptide Y receptor family.

We report isolation of a murine gene, NPYR-D, which predicts an intronless novel G protein-coupled receptor of 375 amino acids. Percent identities of NPYR-D to the clone Y1, Y2, rat Y4/PP1 and human Y4/PP1 receptors are 45, 32, 92 and 76, respectively. Southern blots indicate that NPYR-D and human Y4/PP1 receptor genes are species homologues. Rat [125I]pancreatic polypeptide ([125I]rPP) bound to NPYR-D transfected COS-7 cell membranes with a high affinity, i.e. IC50=90 pM. Pharmacological characterization of [125I]rPP binding showed a rank order of potency of P >> PYY > or = NPY, such that PYY and NPY were at least 5000-fold weaker than PP. Interestingly, [125I]rPYY binding produced the same rank order, but PYY and NPY were only 25-fold weaker than PP, which had an IC50 value of approximately 120 pM. Tissue distribution studies in mouse and humans suggest potential roles of this novel receptor in the gastrointestinal tract, heart, prostate, as well as in neural and endocrine signalling.

Amino Acid Sequence↗
PubMed1996

[The spleen in hereditary spherocytosis].

Hereditary spherocytosis is the most common inherent, autosomal dominant hemolytic anemia. Mild splenomegaly, venostasis and common decrease of while pulp is characteristic for hereditary spherocytosis. Cords are filled with spherocytes, sinuses can be empty or squeezed. Both sinuses and veins include ghost erythrocytes that lost haemoglobin. They are seen light-microscopically in differential interferent contrast. Macrophages are numerous, sinus lining cells are hypertrophic. Erythrophagocytosis is hardly seen by electron microscope. Not all red blood cells are spherocytes. Spherocytes are seen well in electronmicroscopy. We did not observed transition of erythrocytes through sinus walls. In certain circumstances lots of ferritin is seen both intra and extracytoplasmically. Iron accumulation in cords can result in their fibrosis.

Humans↗
PubMed1995

Cloning and chromosomal mapping of three novel genes, GPR9, GPR10, and GPR14, encoding receptors related to interleukin 8, neuropeptide Y, and somatostatin receptors.

We employed the polymerase chain reaction and genomic DNA library screening to clone novel human genes, GPR9 and GPR10, and a rat gene, GPR14. GPR9, GPR10, and GPR14 each encode G protein-coupled receptors. GPR10 and GPR14 are intronless within their coding regions, while GPR9 contains at least one intron. The receptor encoded by GPR9 shares the highest identity with human IL-8 receptor type B (38% overall and 53% in the transmembrane regions), followed by IL-8 receptor type A (36% overall and 51% in the transmembrane domains). GPR10 encodes a receptor that shares highest identity with the neuropeptide Y receptor (31% overall and 46% in the transmembrane domains). The receptor encoded by GPR14 shares highest identity with the somatostatin receptor SSTR 4 (27% overall and 41% in the transmembrane domains). Fluorescence in situ hybridization analysis localized GPR9 to chromosome 8p11.2-p12 and GPR10 to chromosome 10q25.3-q26.

Amino Acid Sequence↗
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↗