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Biomedical subjects

K Piotrowska

Publications and source records attributed to K Piotrowska.

17 recordsLinked to original sources
PubMed2006

Biopharmaceutical characterization of the telomerase inhibitor BRACO19.

PURPOSE: To characterize the telomerase inhibitor and G-quadruplex stabilizing substance 9-[4-(N,N-dimethylamino)phenylamino]-3,6-bis (3-pyrrolodino-propionamido) acridine x 3HCl (BRACO19) in terms of biopharmaceutical properties such as solubility, protein binding, interaction with membrane lipids, cytotoxicity, and permeability across pulmonary epithelial cells. METHODS: Protein binding and interaction with membrane lipids were investigated by two high-performance liquid chromatography methods with immobilized human serum albumin and immobilized phosphatidylcholine, respectively. Cytotoxicity (methyl-thiazolyl-tetrazolium assay) and transport studies were performed with the bronchial cell lines 16HBE14o- and Calu-3, primary human alveolar epithelial cells, and the intestinal cell line Caco-2. Transport experiments were also done in the presence of cyclosporin A (10 microM) and tetraethylammonium chloride (5 mM) and at low temperature (4 degrees C). RESULTS: BRACO19 has good solubility of at least 2 mg/mL in water and in physiological buffers of pH 7.4 and below. Protein binding to human serum albumin was 38%. No interaction with membrane lipids could be found. Cytotoxicity in 16HBE14o-, Calu-3, and human alveolar epithelial cells was in the range of IC50 = 3.5 to 13.5 microM. Caco-2 cells were not affected at concentrations up to 50 microM. No transport of BRACO19 was detected across either cell monolayer in absorptive direction. In secretory direction, permeability was very low, with P (app) values in the range of 0.25 x 10(-7) to 0.98 x 10(-7) cm/s for all epithelial cell cultures tested. The transport was not influenced by cyclosporin A or tetraethylammonium chloride or at 4 degrees C, indicating that no efflux/influx systems or active transport are involved. CONCLUSIONS: From these results, we conclude that the very poor permeability of BRACO19 is its main biopharmaceutical limitation. Further applications will require a suitable formulation to warrant adequate delivery across cellular barriers.

Acridines↗
PubMed2001

Role for sperm in spatial patterning of the early mouse embryo.

Despite an apparent lack of determinants that specify cell fate, spatial patterning of the mouse embryo is evident early in development. The axis of the post-implantation egg cylinder can be traced back to organization of the pre-implantation blastocyst. This in turn reflects the organization of the cleavage-stage embryo and the animal-vegetal axis of the zygote. These findings suggest that the cleavage pattern of normal development may be involved in specifying the future embryonic axis; however, how and when this pattern becomes established is unclear. In many animal eggs, the sperm entry position provides a cue for embryonic patterning, but until now no such role has been found in mammals. Here we show that the sperm entry position predicts the plane of initial cleavage of the mouse egg and can define embryonic and abembryonic halves of the future blastocyst. In addition, the cell inheriting the sperm entry position acquires a division advantage and tends to cleave ahead of its sister. As cell identity reflects the timing of the early cleavages, these events together shape the blastocyst whose organization will become translated into axial patterning after implantation. We present a model for axial development that accommodates these findings with the regulative nature of mouse embryos.

Animals↗
PubMed2001

Blastomeres arising from the first cleavage division have distinguishable fates in normal mouse development.

Two independent studies have recently suggested similar models in which the embryonic and abembryonic parts of the mouse blastocyst become separated already by the first cleavage division. However, no lineage tracing studies carried out so far on early embryos provide the support for such a hypothesis. Thus, to re-examine the fate of blastomeres of the two-cell mouse embryo, we have undertaken lineage tracing studies using a non-perturbing method. We show that two-cell stage blastomeres have a strong tendency to develop into cells that comprise either the embryonic or the abembryonic parts of the blastocyst. Moreover, the two-cell stage blastomere that is first to divide will preferentially contribute its progeny to the embryonic part. Nevertheless, we find that the blastocyst embryonic-abembryonic axis is not perfectly orthogonal to the first cleavage plane, but often shows some angular displacement from it. Consequently, there is a boundary zone adjacent to the interior margin of the blastocoel that is populated by cells derived from both earlier and later dividing blastomeres. The majority of cells that inhabit this boundary region are, however, derived from the later dividing two-cell stage blastomere that contributes predominantly to the abembryonic part of the blastocyst. Thus, at the two-cell stage it is already possible to predict which cell will contribute a greater proportion of its progeny to the abembryonic part of the blastocyst (region including the blastocyst cavity) and which to the embryonic part (region containing the inner cell mass) that will give rise to the embryo proper.

Animals↗
PubMed2000

Effects of preactivation of ooplasts or synchronization of blastomere nuclei in G1 on preimplantation development of rabbit serial nuclear transfer embryos.

Blastomeres from eight-cell-stage rabbit embryos have been fused with enucleated metaphase II oocytes (ooplasts) or with ooplasts that were preactivated before fusion. Preactivation of ooplasts before nuclear transfer (NT) raises the rate of preimplantation development from 15% to 56%, which remains elevated in the next series of NT (48.6% and 47.2% in the second and third rounds, respectively). Transfer of eight-cell embryos from the third round to the recipient resulted in the birth of normal young. Synchronization of blastomere nuclei in the G1 phase with nocodazole before fusion results in 42% morula/blastocyst formation. However, in the second generation of NT embryos, the yield drops to as low as 17%, indicating deleterious effects of the second nocodazole treatment on blastomeres. The calculated number of clones per one round of cloning was 4.5, 3.9, and 3.8 in subsequent series; the highest number of morulae and blastocysts that developed from individual donor embryos after three rounds were 26 and 27, respectively.

Animals↗
PubMed1993

Fine needle aspiration cytology combined with argyrophilic nucleolar organizer regions (AgNORs) in diagnosis of thyroid neoplasms.

NORs are the loops of DNA that contain the sites of ribosomal genes around which the nucleolus is formed during telophase of mitosis. In light microscopy they can be visualized by simple silver staining technique as small dark dots within the nucleus. It has been recognized that in many neoplasms, especially malignant AgNORs are more numerous and often atypical when compared with benign tumors and normal tissue. We have introduced this novel technique to the fine needle cytology of thyroid neoplasms (n = 56). We have analyzed the number, the area of AgNORs, the number of clustered AgNORs in the nucleus and the ratio of AgNOR area to the nuclear area and the area of single AgNOR by means of semiautomatic computerized image analysis. We have studied cytological samples consisting of 7 simple goiters, 7 hyperplasias, 15 follicular adenomas, 7 oxyphilic follicular adenomas, 6 follicular carcinomas, 8 oxyphilic follicular carcinomas, 6 papillary adenocarcinomas. In this study we have demonstrated that some differences in the AgNORs value are associated with the type of tumor rather than with malignancy. Location of the AgNORs seems to be very typical for some types of tumors. For example in oxyphilic neoplasms they form single clusters in the nucleus and in papillary adenocarcinomas they form at least two abundant clusters. In other proliferative lesions of the thyroid gland location of AgNORs is less typical.

Adenoma↗
PubMed1991

The immunological status in Parkinson's disease.

It has been suggested that patients with idiopathic Parkinson's disease have altered functions of the immune system. We determined certain immunological parameters in groups of Parkinson's disease patients who have been i) treated and ii) not been treated, with levodopa. Changes in the immune functions were observed to be more profound in Parkinson's disease patients than in age-matched controls. Treatment with levodopa induced an increase in interleukin-1 synthesis, and in IgM and IgA levels in plasma, which suggest a possible selective action on cells of the immune system.

Age Factors↗
PubMed1989

[Possibilities of objective evaluation of local reactive cell infiltrates in transplantable tumors].

The studies on infiltrations consisting of reactive cells, i.e. lymphocytes, macrophages and neutrophils within and in the vicinity of neoplastic tissue were performed in order to elucidate the nature of the growth and to asses the role of these cells in human tumors. The objective methods for both qualitative and quantitative evaluation of the infiltrating cells are necessary to obtain comparable results. We report our studies on the numbers and types of reactive cells present in 3 transplantable murine tumors with different immunogenicity (SaL-1, LLC, MCA-Sa). The cytological characterization of cells was performed as following: after enzymic digestion of the tissue the cell suspension was then passed through Millipore filters and dyed. The preliminary evaluation of the percentage of lymphocytes T found in the tumor infiltrations was performed using cytotoxicity test with monoclonal antithymocytic serum (Monoclonal Anti-Mouse Thy 1, 2). We have shown that there are differences in the number and type of reactive cells in infiltrations of the three different tumor tested. With the increasing mass of tumors the percent of reactive cells decreases proportionally.

Animals↗
PubMed1976

Screening by negative chemical ionization mass spectrometry for environmental contamination with toxic residues: Application to human urines.

A screening procedure based on solvent extraction with minimal clean up followed by examination with negative chemical ionization mass spectrometry has been developed for organochlorine residues and related compounds with masses greater than 130 daltons. The procedure has been made quantitative for analysis of pentachlorophenol residues. A limited survey of human urines indicated extensive contamination of the subjects, studied at parts per billion and higher levels, with pentachlorophenol, 2, 4, 5-trichlorophenoxy acetic acid, other polychlorophenoxy acids, and numerous unknown compounds. In an attempt to define the source of the contamination, the screening procedure was applied to samples of environmental substrates. The results suggest the food chain as one significant source of the contamination. A preliminary study of organochlorine compounds in human seminal fluid showed pentachlorophenol and other organochlorine residues in every sample, a result which suggests that this area may merit additional monitoring.

Humans↗
PubMed1976

Multiresidue screening by negative chemical ionization mass spectrometry of organic polychlorides.

A multiresidue procedure, based on negative chemical ionization (NCI) mass spectrometry, for analyzing organochlorine residues in environmental substrates is described. The procedure is capable of routinely detecting about 1 ng unknown organochlorine residues. Semi-quantitative data (order of magnitude) may be obtained for pentachlorophenol and 2,4,5-trichlorophenoxyacetic acid residues by calibration with internal p-chlorobenzophenone. Lipid-rich substrates were resolved into acidic and neutral fractions, and both fractions were further purified by gel permeation chromatography (GPC) prior to NCI analysis. In spite of the fact that recoveries were often low, the overall sensitivity for residues in lipid-rich substrates appeared to be higher than when the GPC step was omitted.

Animals↗
PubMedDate not supplied

[Secretion of tumor necrosis factor alpha (TNF-alpha) by peripheral blood monocytes in patients with multiple sclerosis and subacute sclerosis panencephalitis].

TNF alpha production by peripheral blood monocytes was studied in seventeen patients with a recent exacerbation of MS, thirteen with remission of MS and fourteen patients with SSPE. Monocytes from both MS groups spontaneously secreted high amounts of TNF alpha in vitro. Addition of lipopolisaccharide could not stimulate further synthesis of TNF alpha. In SSPE spontaneous and stimulated TNF alpha release did not differ from that in the control group. The observed changes in TNF alpha release in MS patients could play a role in the pathogenesis of the disease.

Cells, Cultured↗
PubMedDate not supplied

Immunological status in Huntington's disease.

The immunological status of patients with Huntington's disease was studied and compared with that of an age-matched control group. No remarkable abnormalities in lymphocyte subpopulations were observed. The percentage of B cells, CD4+, CD8+, DR+ cells and stimulated cells bearing Tac receptors remained unchanged. The proliferative response to mitogens and the production of interleukin-1 (Il-1) were decreased, whereas the IgG level was increased. It is possible that changes in the levels of neurotransmitters affect the immunological function in basal ganglia disease.

Adult↗
PubMedDate not supplied

The test of non-specific cell-mediated response in animals with transplantable tumours stimulated with calf thymus extract.

Investigations were carried out on the non-specific cell-mediated response in mice with transplantable tumours: LLC in mice C57Bl and F1(C57Bl X C3H), and SAL-l tumour in Balb/c mice. The malignant cells were implanted subcutaneously for observation of changes in the non-specific cell-mediated response at the time of the local growth of the tumour, and injections into the vein or into the foot-pad were made for studying the non-specific cell-mediated response at the time of tumour dissemination. In each series of the experiments the animals received an extract of calf thymus--the preparation TFX-Polfa. The control groups had the tumour cells implanted or injected but were not given TFX. For determining the non-specific cell-mediated response the animals were immunized with picryl chloride. In both experimental models, that is with subcutaneous implantation and with injections intravenously or into the foot-pad a decrease of the non-specific cell-mediated response was observed progressing gradually with extension of the tumours. Long-term administration of TFX in doses of 0.1 mg per mouse prevented the decrease of the non-specific cell-mediated response in the first place in mice with subcutaneous implantations. In mice with malignant cells injected intravenously or into the foot-pad TFX administration had no evident effect on the value of the test. This observation suggests that TFX prevents the development of a secondary immune deficit in mice with subcutaneous transplanted tumours--that is mainly at the time of local growth of the tumour, but is of little use in the phase of tumour dissemination.

Adjuvants, Immunologic↗