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V Kren

Publications and source records attributed to V Kren.

At least 145 records · Page 8Linked to original sources

Contribution to the morphometry of limb bud structures in the normodactylous and polydactylous rat. I. Apical ectodermal ridge.

The height of the apical ectodermal ridge on limb buds of the embryo laboratory rat was studied in the polydactyly-luxate syndrome and compared with the controls. The following findings were obtained: (a) On the 14th embryonal day, prior to the development of the anlage of mesenchymal condensates, the AER is higher in polydactylous animals as compared with the controls. (b) On the 15th, 16th and 17th embryonal day the height of the AER in the praeaxial region of the polydactylous limb bud largely predominates over the controls. A comparison of the height of the AER above digital rays and interdigital grooves of polydactylous and normodactylous animals does not thus exhibit any marked differences. This fact is attributed to the existence of more powerful induction processes of the underlying mesenchymal component where rudiments of supernumerary digital rays are formed.

Animals↗

Contribution to the morphometry of limb bud structures in the normodactylous and polydactylous rat. II. Density of filopodia in the subectodermal zone.

In hindlimb buds of normodactylous and polydactylous embryos in the stage of the 16th and 17th embryonal day the mesenchymal region, closely adjoining the site below the AER, was investigated. This space is called the subridge zone and is filled with a large amount of variously formed processes of mesenchymal cells, chiefly with filopodia. With the use of the morphometric point-couting method it was found that in normodactylous limb buds the density of filopodia in the given area of the subridge zone was 2.15% as compared with the 6.48% representation of filopodia in the same zone of polydactylous animals. Numerous filopodia localized right under the AER established connection between the mesenchyma and the intact basal membrane, and their higher density is undoubtedly related to the existence of the maintenance factor.

Animals↗

The significance of genetic factors for thalidomide teratogenicity in the Norway rat.

Thalidomide teratogenicity was tested on a model based on the system of congenic strains of the laboratory rat, including the mutant allele lx, which determines the polydactyly-luxate syndrome. The phenotypic expression of the allele lx changes according to the genetic background of the carrier and also according to factors of the external environment. On a hybrid genetic background LEW/BN the allele lx acts as recessive, and heterozygotes +/lx are unaffected. In a number of experiments it was proved, however, that these hybrids (LEW/BN, +/lx) had an increased sensitivity to the induction of limb malformations (polydactyly, tibial hemimelia, oligodactyly) by various teratogens. Thalidomide was administered on the 12th day of pregnancy by the intraperitoneal route in a mixture of Tween 20 with saline (1:3) in doses of 25, 50 and 200 mg/kg to females with genetic background LEW that were purposely mated with males of the BN or BN.lx strains. The produced progeny had genotypes LEW/BN, +/+ or LEW/BN, +/lx. In offsprings that had in the genotype the mutant allele lx in a heterozygous condition (+/lx) preaxial polydactyly of hind limbs developed after all the thalidomide doses tested. This malformation occurred in 17 out of 18 litters, altogether in 97 out of 162 foetuses +/lx, i.e. in 59.9%. In the progeny without the mutant allele (genotype +/+) polydactyly did not develop in any of the 108 cases. Control foetuses +/+ the mothers of which had been administered only Tween 20 with saline remained unaffected, while in control foetuses +/lx polydactyly developed in 8.1% (3 cases). The result demonstrates thalidomide teratogenicity in the laboratory rat where it has not been proved unambiguously so far. The teratogenic effect is the outcome of the interaction of thalidomide with the mutant allele lx. At the same time there is emphasized the importance of the genotype of the experimental animals in the testing of teratogens.

Animals↗

Patterns of physiological cell death and mitoses in the apical ectodermal ridge in normodactylous and polydactylous rat limb buds. A quantitative evaluation.

Limb buds in normally developing foetal rats and rats with the polydactyly-luxate syndrome at day 14 and 15 of intrauterine growth were studied at the optical and electron microscopic levels. Four sets of limb buds were collected and evaluated: 14th e.d.N., 14th e.d.P., 15th e.d.N., and 15th e.d.P. (e.d. embryonic day, N - normodactylous, P - polydactylous); they were studied for apical ectodermal ridge development with reference to the rates of cell death and mitosis. Both phenomena were evaluated quantitatively. A significant difference was found in the rate of physiological cell death, which was far lower in polydactylous (4.33 and 28.73) as compared with normodactylous individuals (62.40 and 82.11 cell deaths per 300 cells in the ridge on days 14 and 15). The difference found documents a considerable retardation in cell death rate in the polydactylous apical ectodermal ridge epithelium. Physiological cell death is associated with a process called apoptosis, which is characterized by the presence of "apoptotic bodies" in the cytoplasm of epithelial cells and in the intercellular space. The total number of mitoses in the ridge epithelium was relatively low (4.63 - 6.33 per 300 cells) and the differences between norm and polydactyly were not statistically significant.

Animals↗

An analysis of spontaneous hypertension in spontaneously hypertensive rats by means of new recombinant inbred strains.

The mode of blood pressure inheritance and some genetic markers of spontaneous hypertension were evaluated in a new set of recombinant inbred (RI) strains obtained by crossing of normotensive (BN.lx) and hypertensive (SHR) progenitor strains. Blood pressure values of RI strains were continuously distributed between both progenitor strains, although normotensive strains slightly prevailed. Statistical analysis suggested that there are three major genes and multiple minor genes responsible of the determination of spontaneous hypertension. The association between blood pressure and gene(s) within RT1 complex or gene(s) closely linked to it was found by RI strain analysis. This suggestion was confirmed by the detection of significant difference in blood pressure between SHR and SHR.1N congenic strains. Our results indicate that RT1 complex gene(s) may be involved in the development of high blood pressure.

Animals↗

Spontaneously metastasizing rat sarcomas LW13K2 and RPS: assessment by the immunogenetic test of malignancy, in vitro behaviour and karyology.

Populations of LW13K2 sarcoma derivatives were compared for their malignancy, patterns of cell behaviour in vitro (dynamic morphology and migration) and karyological pattern. The following tumour cell populations were used: the original LW13K2 sarcoma from inbred LEW/CUB rats, RPS sarcoma derived from it by neoplastic progression, four cell populations isolated in vitro from metastases of a syngeneic LEW-CUB strain rat with RPS tumour and four neoplastic cell populations isolated from spontaneous metastases shed by RPS sarcoma in allogeneic rats, differing from LEW/CUB in weak alloantigenic loci. Although RPS tumour did not grow progressively in MHC-different recipients (while the original LW13K2 tumour did), it grew progressively and metastasized in all groups of non-MHC allogeneic recipients. Parallel with the metastatic potential patterns of in vitro behaviour, such as an increased incidence of the quasi-stellate morphotype at slightly acid culture conditions endowed with enhanced changeability of the cell shape and migrational activity, were found. Cytogenetic analysis demonstrated rather stable chromosomal patterns over the cascade of neoplastic progression from LW13K2 sarcoma over RPS sarcoma to freshly isolated metastases. This indicated that the apparent neoplastic progression observed in the cell populations derived from LW13K2 sarcoma is with high probability not due to the selection at the chromosomal level.

Animals↗

Ganglioside composition in experimental tumors with different growth properties.

The composition of gangliosides was studied in four fibrosarcomas (FL, FLA, FLB, FLC) induced in the Lewis rat by Ferridextran, and in two clones of a spontaneous Lewis rat mammary sarcoma (C-1-SAM LEW and C-2-SAM LEW) and two supertransformed clones (S-174 and S-271) derived from these clones, using the B77 virus. The malignancy of the Lewis tumors was tested in terms of their ability to outgrow the RT-5 barrier in LEW.1x rats and expressed as the loss-rate of LEW.1x rats. As for the Ferridextran-induced tumors, the FL was the only one to have been rejected in nearly 100% of the LEW.1x recipients. Following presensitization with FL the other tumors were also rejected, though not at a rate of 100%. The rat loss-rate was: FL--0%, FLC--23.5%, FLB--36.5%, and FLA--82.6%. As malignancy increased, the composition of gangliosides showed signs of progressive simplification indicating a step-by-step repression of ganglioside biosynthesis involving first the disialoganglioside and subsequently also the monosialoganglioside pathways. Some less distinct decrease (but significant at the 5% level of probability) of gangliosides of the disialoganglioside pathway and an increase of the simplest ganglioside (GM3) were observed between the C-1 clone of SAM LEW and its S-174 supertransformant. However, the changes, especially in the C-2 clone and its supertransformant, were not such as would suggest a marked defect in the biosynthesis of gangliosides.

Animals↗

Effect of clomiphene on fatty acids, sterols and membrane fluidity in clavine producing Claviceps purpurea strains.

Clomiphene depressed the growth and enhanced clavine production of Claviceps purpurea strains 129,35 and 59. Mycelial content of 18:2 and 16:0 fatty acids decreased, whereas that of 18:1 and 18:0 acids increased. In the mutant strain 59 clomiphene, triadimefon and ergosterol stimulated the impaired function of chanoclavine cyclase. Their effect was counteracted by plant oil. Clomiphene decreased the content of total lipids (44%), triglycerides (32%), sterols (22%) and sterol/phospholipid molar ratio. The PC/PE ratio was 9X increased. Clomiphene and triadimefon enhanced membrane fluidity of protoplasts, ergosterol and oil reverted their effect.

Claviceps↗

Spontaneous acute lymphoblastic leukemia in Sprague-Dawley rats. II. Cytogenetic analysis of nine individual leukemias.

Nine spontaneous acute lymphoblastic leukemias (SD1-SD9) in Sprague-Dawley rats were investigated cytogenetically by G-banding. The chromosome numbers of metaphase cells in all studied SD leukemias were near diploid and in all leukemias numerical or structural abnormalities were found. Affected were chromosomes No. 11, 2, 13 and 1. A common finding in most leukemias was trisomy 11 observed either as simple trisomy (SD1, SD4 and 2 clones of SD6), or the translocation form of trisomy (SD3), or the tandem translocation t(11;13) in SD7, or the Robertsonian fusion -rob(2;11) in SD5. In SD9 and one cell clone of SD8 no apparent trisomy was found, but the cells contained an 11q+ marker. Among the rearranged chromosomes, chromosome 2 was most frequently involved. Der No. 2 with terminal deletion was found in some of SD3 metaphases and a probable partial duplication of chromosome 2 was found in SD6. The finding of trisomy 2 in SD5 and SD6 occurred rarely. Further structural rearrangements concerned No. 13, the involvement of which was evident in the 13q+ marker typical of SD2, one cell clone of SD6, SD7 and SD8 leukemias. 1q+ aberration was the common finding in SD3 and SD5, while 1q-was observed in all SD6 metaphases. According to the cytogenetic examination of SD leukemias, we considered that the changes of chromosomes 11, 2, 13 and 1 were nonrandom. Based on the similarity of chromosomal rearrangements in individual leukemias, probable breakpoints on the affected chromosomes could be determined. 11cen, 11q12, 2q32-33, 2q16, 13q22, 1q43 and 1q54 were found to be the most frequently afflicted regions in SD leukemias.

Aneuploidy↗