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Biomedical subjects

V Kren

Publications and source records attributed to V Kren.

At least 127 records · Page 7Linked to original sources
PubMed1993

Cytostatic effect of 9-(2-phosphonomethoxyethyl) adenine (PMEA). I. Lymphatic leukemia KHP-Lw-I in Lewis rats.

PMEA was administered i.p. daily on 10 consecutive days to inbred LEW rats inoculated with leukemic lymphoblastic cells KPH-Lw-I. The treatment was started 24 h after the inoculation. The observed cytostatic effects consisted in a significant prolongation of survival time associated with a suppression of the number of bone marrow leukemia cells with characteristic chromosomal marker of KPH-Lw-I leukemia as well as with a depression of the number of lymphoblasts in the blood.

Adenine↗
PubMed1993

Antimitotic and teratogenic effects of acyclic nucleotide analogues 1-(S)-(3-hydroxy-2-phosphonomethoxyethyl)cytosine (HPMPC) and 9-(2-phosphonomethoxyethyl) adenine (PMEA).

The acyclic nucleotide analogues, HPMPC and PMEA, differ in their in vitro effect on the genetic material of eukaryotic cells. While HPMPC exerts a cytostatic effect on eukaryotic cells in vitro, PMEA has a genotoxic activity. These results correspond with the mode of embryotoxic action of these compounds: HPMPC exhibits a general embryolethal effect, whereas PMEA is apparently teratogenic and interacts with the mutant allele producing preaxial polydactyly of the hind limbs.

Adenine↗
PubMed1993

Prevention of acute graft-versus-host disease in rats using 9-(2-phosphonomethoxyethyl) adenine (PMEA).

Severe graft-versus-host disease (GVHD) developed following intravenous administration of parental BN.lx lymphoid cells into (SHR x BN.lx)F1 animals. Clinical symptoms, including foot-pad hyperemia, slobbering, melaena, progressive weight loss leading to death within 3 to 4 weeks, can be completely abrogated by 8 injections of PMEA starting 1 h after cell administration. Practically normal histological findings in PMEA-treated animals contrasted with nearly complete damage of bone marrow, lymphoid infiltration of salivary glands and even ulceration with hemorrhage of the epidermoid part of the stomach in untreated control GVHD animals.

Acute Disease↗
PubMed1992

Assignment of rat linkage group V to chromosome 19 by single-strand conformation polymorphism analysis of somatic cell hybrids.

The rat provides a number of important models of human genetic disease; however, the rat genetic map has not been extensively developed. Although most rat chromosomes carry several gene assignments, some major linkage groups (LG) remain to be mapped. To determine the chromosome location of the largest unmapped linkage group in the rat (LG V containing multiple carboxylesterase loci), we used single-strand conformation polymorphism analysis to identify the rat esterase-10 gene in a panel of rat x mouse somatic cell hybrids. We found that the carboxylesterase gene family and hence LG V are located on rat chromosome 19. We have also confirmed the assignment of the angiotensinogen gene to rat chromosome 19 and have used a large set of recombinant inbred strains to map two anonymous variable number of tandem repeat (VNTR) markers to this chromosome. The current findings bring the total number of genes assigned to rat chromosome 19 from 3 to 19 and provide further evidence of substantial homology between this chromosome and chromosome 8 in the mouse.

Angiotensinogen↗
PubMed1992

Platelet aggregation in spontaneous hypertension: genetic determination and correlation analysis.

OBJECTIVE: Hyper-responsive platelets are often found in essential hypertension. It has also been suggested that in hypertensive patients platelets may serve as an easily accessible indicator of abnormalities in contractile cell function. To test these suggestions, we analysed the relationship between platelet aggregation and genetic hypertension in the rat. METHODS: Linear regression analysis of mean values of recombinant inbred strains was used to evaluate the relationship between blood pressure and ADP-induced platelet aggregation. RESULTS: ADP-induced platelet aggregation in platelet-rich plasma in spontaneously hypertensive rats (SHR) was significantly decreased compared with in normotensive Brown Norway (BN) rats. However, in recombinant inbred strains, derived from (SHR x BN) F2 hybrids, correlation analysis revealed that platelet aggregation and blood pressure are independent traits. CONCLUSIONS: The present results suggest strongly that spontaneous hypertension and platelet hypo-aggregability in SHR were linked together by chance due to drift during selective inbreeding. The absence of a correlation between the two traits also indicates that alterations in platelet function in essential hypertension, often found in population-based studies, may have to be reaffirmed in genetically better-defined situations, e.g. by pedigree analysis.

Animals↗
PubMed1992

Restriction fragment length polymorphism of hsp70 gene, localized in the RT1 complex, is associated with hypertension in spontaneously hypertensive rats.

Previous studies from our laboratory have demonstrated that the intermediate phenotype of thermosensitivity is present in hypertensive mice and rats. Increased expression of hsp70 caused by increased transcription rate was demonstrated in vivo, in organs, and in cultured cells from spontaneously hypertensive rats and hypertensive mice. In this study, a polymorphism of this gene was revealed with BamHI enzyme by using a human hsp70 probe. A 4.4-kb fragment was visualized in normotensive rats (Brown-Norway BN.lx and Sprague-Dawley), and a 3.0-kb fragment was found in spontaneously hypertensive rats (SHR) of three different origins and in Wistar and Buffalo rats. Both fragments were present in the Wistar-Kyoto rat strain. The present study mapped the polymorphism of hsp70 into the RT1 complex in BN.1K and SHR.1N congenic strains. The hsp70 restriction fragment length polymorphism is associated with a blood pressure difference of 15 mm Hg in recombinant inbred strains. These results justify the search for a mechanism by which hsp70 could influence blood pressure.

Animals↗
PubMed1992

Association of red blood cell sodium leak with blood pressure in recombinant inbred strains.

Red blood cell Na+ content as well as ouabain-resistant Na+ and Rb+ (K+) transport (susceptible or resistant to inhibition by loop diuretics) were determined in spontaneously hypertensive rats (SHR) and normotensive Brown Norway (BN) rats the erythrocytes of which were incubated in either saline or Mg(2+)-sucrose medium. Elevated ouabain-resistant Na+ net uptake contrasted with slightly decreased red blood cell Na+ content in SHR compared with BN rats. Acceleration of furosemide- and bumetanide-sensitive Na+ fluxes contributed to enhanced ouabain-resistant Na+ influx into SHR erythrocytes in saline medium, whereas higher furosemide- or bumetanide-resistant Na+ efflux caused greater ouabain-resistant Na+ efflux in Mg(2+)-sucrose medium. Furosemide- and bumetanide-resistant Rb+ leaks were augmented in SHR erythrocytes. The association of the disclosed ion transport alterations with blood pressure was examined in 20 recombinant inbred strains derived from F2 SHR x BN hybrids. Ouabain-resistant Na+ uptake as well as furosemide- and bumetanide-resistant Na+ inward leaks (but not red blood cell Na+ content or furosemide- and bumetanide-sensitive Na+ net uptake) cosegregated with systolic and pulse pressures but not diastolic pressure of the recombinant inbred strains. In contrast, neither ouabain-resistant Na+ efflux nor any component of ouabain-resistant Rb+ uptake correlated positively with blood pressure of the recombinant inbred strains. Increased ouabain-resistant Na+ influx was compensated for by accelerated ouabain-sensitive Na+ extrusion because red blood cell Na+ content was not elevated in the hypertensive strains. Thus, high cell Na+ turnover rates might be related to genetic hypertension if an altered Na+ inward leak would be less effectively compensated for in tissues involved in cardiovascular regulation.

Analysis of Variance↗
PubMed1992

Teratogenicity testing based on the interaction with a mutant allele.

The system of congenic strains of the laboratory rat carrying the mutant allele lx which is determining the polydactyly-luxate syndrome (PLS) was used for testing teratogenicity of six compounds from different pharmacological groups (cyclophosphamide, cyadox, carbadox, imipramine, verapamil, TIA). The interaction of the mutant lx allele with cyclophosphamide was highly significant (P less than 0.001) involving both polydactyly and tibial hemimely. Significant interaction with the lx allele was also proved after cyadox and carbadox treatment when compared with lx allele penetrance in LEW/BN, +/1x heterozygotes (P less than 0.01 and 0.05). In accord with our previous experiments, the teratogenic activity of the compounds tested seems to be connected with the ability to interact with nucleic acid structure and/or function.

Abnormalities, Drug-Induced↗
PubMed1991

The rat renin gene: assignment to chromosome 13 and linkage to the regulation of blood pressure.

It has recently been suggested that in the rat, sequence variation in the renin gene or closely linked genes may have the capacity to affect blood pressure and contribute to the pathogenesis of hypertension. To map the chromosomal location of the rat renin gene and to investigate its relationship to the inheritance of increased blood pressure, we studied a panel of rat x mouse somatic cell hybrids and a large set of recombinant inbred (RI) strains derived from spontaneously hypertensive rats (SHR) and normotensive Brown-Norway (BN) rats. We have found that in the rat, the renin gene is located on chromosome 13 and that it belongs to a conserved synteny group located on chromosome 1 in man and mouse. We have also found the median blood pressure of the RI strains that inherited the renin allele of the SHR to be greater than that of the RI strains that inherited the renin allele of the normotensive BN rat. These findings, together with the results of previous studies, suggest that in the rat, sequence variation in the renin gene, or in genes linked to the renin locus on chromosome 13, may have the capacity to affect blood pressure.

Animals↗
PubMed1991

Cosegregation of blood pressure with a kallikrein gene family polymorphism.

It has recently been proposed that sequence variation in the gene coding for tissue kallikrein might be involved in the pathogenesis of hypertension. However, molecular evidence of an association between a sequence alteration in the kallikrein gene family and the transmission of increased blood pressure has never been reported. In 32 recombinant inbred (RI) strains derived from the spontaneously hypertensive rat (SHR) and the normotensive Brown Norway rat (BN), we investigated whether a restriction fragment length polymorphism (RFLP) marking the kallikrein gene family cosegregated with blood pressure. In the RI strains that inherited the kallikrein RFLP from the SHR progenitor strain, the median systolic, diastolic, and mean arterial pressures were significantly greater than in the RI strains that inherited the kallikrein RFLP from the BN progenitor strain. These findings suggest that in the rat, sequence variation in the kallikrein gene family, or in closely linked genes, may have the capacity to affect blood pressure.

Animals↗
PubMed1991

Bioconversions of ergot alkaloids.

Ergot alkaloids are very important pharmaceutical substances with wide medical use. Their bioproduction is usually followed by chemical modification. Bioconversions of ergot alkaloids on an industrial scale have become more important in recent years. The aim of this study is to collect the available data on ergot alkaloid bioconversions and to show their potential applications. The paper deals with conversions of clavines, e.g. biooxidations, glycosylations of the alkaloids, and bioconversions of lysergic acid derivatives. A part of it is aimed at bioconversions of ergot alkaloids in mammalian organisms and obtaining their metabolites by biotransformation. The use of immobilized systems and cofermentation is also discussed.

Animals↗
PubMed1990

Genetic determination of heart and kidney weights studied using a set of recombinant inbred strains: the relationship to blood pressure.

The effects of genetic factors and blood pressure levels on heart and kidney weights were estimated in a set of recombinant inbred (RI) strains obtained by crossing normotensive rat (BN.lx) and genetically hypertensive rat (SHR) progenitor strains. Renal or cardiac hypertrophy in several normotensive RI strains, together with low organ weights in some hypertensive strains, indicate that genetic factors play an important role in heart and kidney weight determination. In RI strains, there was a slight positive correlation between systolic blood pressure and relative heart weight, while relative kidney weight correlated negatively with blood pressure. Indeed, the analysis of the degree of genetic determination in RI strains revealed higher values for the relative kidney weight than for the relative heart weight. Blood pressure has a lower degree of genetic determination than both organs. Several polymorphic loci were found to be associated with organ weight determination. Thus, the analysis of organ weights in RI strains revealed the influence of primary genetic factors rather than secondary blood pressure effects.

Analysis of Variance↗