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S Mazur

Publications and source records attributed to S Mazur.

At least 19 recordsLinked to original sources
PubMed2000

A thermodynamic and structural analysis of DNA minor-groove complex formation.

As part of an effort to develop a better understanding of the structural and thermodynamic principles of DNA minor groove recognition, we have investigated complexes of three diphenylfuran dications with the d(CGCGAATTCGCG)(2) duplex. The parent compound, furamidine (DB75), has two amidine substituents while DB244 has cyclopentyl amidine substituents and DB226 has 3-pentyl amidines. The structure for the DB244-DNA complex is reported here and is compared to the structure of the DB75 complex. Crystals were not obtained with DB226 but information from the DB75 and DB244 structures as well as previous NMR results on DB226 indicate that all three compounds bind in the minor groove at the AATT site of the duplex. DB244 and DB75 penetrate to the floor of the groove and form hydrogen bonds with T8 on one strand and T20 on the opposite strand while DB226 forms a complex with fewer interactions. Binding studies by surface plasmon resonance (SPR) yield -delta G degrees values in the order DB244>DB75>DB226 that are relatively constant with temperature. The equilibrium binding constants for DB244 are 10-20 times greater than that for DB226. Isothermal titration calorimetric (ITC) experiments indicate that, in contrast to delta G degrees, delta H degrees varies considerably with temperature to yield large negative delta Cp degrees values. The thermodynamic results, analyzed in terms of structures of the DNA complexes, provide an explanation of why DB244 binds more strongly to DNA than DB75, while DB266 binds more weakly. All three compounds have a major contribution to binding from hydrophobic interactions but the hydrophobic term is most favorable for DB244. DB244 also has strong contributions from molecular interactions in its DNA complex and all of these factors combine to give it the largest-delta G degrees for binding. Although the factors that influence the energetics of minor groove interactions are varied and complex, results from the literature coupled with those on the furan derivatives indicate that there are some common characteristics for minor groove recognition by unfused heterocyclic cations that can be used in molecular design.

Base Sequence↗
PubMed2000

Elevating the island: the simplest method of delaying the TRAM flap.

Vascular compromise is a relatively frequent complication of breast reconstruction performed with the use of pedicled transverse rectus abdominis musculocutaneous (TRAM) flaps. The authors present their experience in delaying TRAM flaps by preelevating the island 7 to 10 days before flap transfer. The skin island is fully incised and raised from the lateral tip to the lateral border of the rectus muscle on one side, and is raised from the tip to the midline on the opposite side. The inferior epigastric pedicle of the rectus muscle remains intact. This method was used in 55 patients. No total flap loss, and only two cases (3.6%) of partial flap necrosis were observed. Preelevating the island is a very simple and effective method of TRAM flap delay, alternative to the ligation of the inferior epigastric pedicle.

Female↗
PubMed1999

Efficient gene delivery to quiescent interleukin-2 (IL-2)-dependent cells by murine leukemia virus-derived vectors harboring IL-2 chimeric envelope glycoproteins.

Interleukin-2 (IL-2) is a cytokine that induces the proliferation of certain IL-2 receptor expressing quiescent cells. Human IL-2 was fused to the amino-terminus of amphotropic murine leukemia virus (MLV) envelope glycoproteins. Retroviral vectors were pseudotyped with both the IL-2 chimeric envelope and the wild-type amphotropic MLV envelope. The chimeric IL-2 glycoproteins were incorporated on retroviral vectors and the IL-2-displaying vector particles could bind specifically to cell surface IL-2 receptors. In addition, the IL-2-displaying vectors could infect proliferating cells through amphotropic receptors irrespective of whether the cells expressed the IL-2 receptor. IL-2-displaying vector particles could also transiently stimulate the cell cycle entry and proliferation of several IL-2-dependent cell lines. Finally, retroviral vectors displaying IL-2 could efficiently transduce G0/G1-arrested cells expressing the IL-2 receptor at a 34-fold higher efficiency compared with vectors with unmodified envelopes. This new strategy, whereby C-type retroviral vector particles display a ligand that activates the cell cycle of the target cells at the time of virus entry, may represent an alternative to lentivirus-derived retroviral vectors for the infection of quiescent cells. In addition, upon infection of an heterogeneous population of nonproliferating cells, MLV-retroviral vectors that display cytokines/growth factors will allow the transgene of interest to be integrated specifically in quiescent cells expressing the corresponding cytokine/growth factor receptor.

Cell Cycle↗
PubMed1999

Informed consent to serum screening for Down syndrome: are women given adequate information?

To assess the information given to women during a maternal serum screening (MSS) programme, we prospectively applied a questionnaire to 504 pregnant women attending for amniocentesis after a screen-positive result. The survey based on 200 usable questionnaires (39.7 per cent of our study population) showed that MSS was imposed as mandatory by 41.5 per cent of providers and done without their patients' agreement by 16 per cent. After release of the test results, 6.5 per cent of women believed that they were carrying a Down syndrome-affected fetus and 21.5 per cent thought the risk was about 50-50. A total of 38.5 per cent of the pregnant women were not informed of the risk of miscarriage after amniocentesis and 67.5 per cent believed that there was no possibility of a false-negative result with MSS. Information given over the telephone was particularly poorly understood compared with information provided during an outcome visit, since women who learned of their test result during such a visit scored significantly higher (69 per cent) when questioned about the risk of carrying a Down syndrome-affected fetus, compared with women informed of their test results by telephone (38.7 per cent) or by letter (47 per cent). We therefore suggest routine consultation with an antenatal care professional before testing to enable pregnant women to give their informed consent to MSS.

Amniocentesis↗
PubMed1998

Oxidative DNA damage processing and changes with aging.

Living organisms are constantly exposed to oxidative stress from environmental agents and from endogenous metabolic processes. The resulting oxidative modifications occur in proteins, lipids and DNA. Since proteins and lipids are readily degraded and resynthesized, the most significant consequence of the oxidative stress is thought to be the DNA modifications, which can become permanent via the formation of mutations and other types of genomic instability. Many different DNA base changes have been seen following some form of oxidative stress, and these lesions are widely considered as instigators for the development of cancer and are also implicated in the process of aging. Several studies have documented that oxidative DNA lesions accumulate with aging, and it appears that the major site of this accumulation is mitochondrial DNA rather than nuclear DNA. The DNA repair mechanisms involved in the removal of oxidative DNA lesions are much more complex than previously considered. They involve base excision repair (BER) pathways and nucleotide excision repair (NER) pathways, and there is currently a great deal of interest in clarification of the pathways and their interactions. We have used a number of different approaches to explore the mechanism of the repair processes, and we are able to examine the repair of different types of lesions and to measure different steps of the repair processes. Furthermore, we can measure the DNA damage processing in the nuclear DNA and separately, in the mitochondrial DNA. Contrary to widely held notions, mitochondria have efficient DNA repair of oxidative DNA damage and we are exploring the mechanisms. In a human disorder, Cockayne syndrome (CS), characterized by premature aging, there appear to be deficiencies in the repair of oxidative DNA damage in the nuclear DNA, and this may be the major underlying cause of the disease.

Aging↗
PubMed1995

Episomal amplification or chromosomal integration of the viral genome: alternative pathways in hamster polyomavirus-induced lymphomas.

The state and expression of the hamster polyomavirus genome in a large panel of virus-induced lymphomas have been investigated. The viral genome is present within tumor cells either as abundant nonrandomly deleted extrachromosomal copies or as a single copy integrated into cellular DNA. We show that these two physical states are likely to be functionally equivalent: first, deletion and integration of the viral genome both inactivate the late coding region; second, the amount of viral early RNAs yielded by a single integrated copy appears to be very similar to that associated with several thousands of extrachromosomal copies of the viral genome. These data underline two essential requisites for hamster polyomavirus to become lymphomagenous: suppression of the late coding functions of the viral genome and expression of the viral oncogenes above a threshold level.

Animals↗
PubMed1994

In vivo replication of the hamster polyomavirus genome and generation of specific deletions in the process of lymphomagenesis.

Hamster polyomavirus (HaPV) causes lymphomas when injected into newborn hamsters. These tumors are virus-free but accumulate large amounts of deleted extrachromosomal viral genomes. In order to identify the major sites of virus replication in animals, we have monitored the HaPV DNA present in different organs at various times after injection. The data demonstrate that viral replication preferentially occurs in lymphoid organs. Lymphoma-associated viral genomes display specific deletions. PCR analysis shows that such viral genomes are the only variants detectable in infected animals, suggesting that they are generated by a specific cellular mechanism. We have tested the possible role of the lymphoid cell-specific V(D)J recombination activity in the generation of these specific variants. Our results indicate that this mechanism is not solely responsible for the viral genome rearrangement, if involved at all.

Animals↗
PubMed1993

Viral genomes maintained extrachromosomally in hamster polyomavirus-induced lymphomas display a cell-specific replication in vitro.

Hamster polyomavirus causes lymphomas when injected into newborn Syrian hamsters. Large amounts of extrachromosomal viral genomes are accumulated in the lymphoma cells. These genomes are characterized by deletions affecting the late coding region as well as a specific part of the noncoding regulatory region. By contrast with wild-type genomes, lymphoma-associated genomes replicate in a lymphoblastoid cell line but not in a fibroblastic cell line. The deletion acts in a cis-dominant manner and is the primary determinant of this host-range effect on replication. The boundaries of the regulatory region necessary for viral DNA replication in the two cell contexts have been defined. The regulatory region can be functionally divided in two domains: one domain (distal from the origin of replication) is necessary for viral genome replication in fibroblasts, whereas the other domain (proximal to the origin of replication) is functional only in the lymphoblastoid cell context and contains the sequence specifically conserved in the lymphoma-associated genomes. This sequence harbors a motif recognized by a lymphoblastoid cell-specific trans-acting factor.

Animals↗
PubMed1993

[Abdominal actinomycosis imitating non-operable stage of cancer].

In a 44-year-old woman on the basis of short hospital medical observation and gynaecological consultations, malignancy of reproductive organs was preliminarily diagnosed. During the operation the gynaecological-surgical team confirmed the presence of generalized neoplastic process in the abdominal cavity. In the obtained surgical specimens actinomycosis was diagnosed by histological examination. Longterm antibiotic therapy caused an improvement of the patient's condition, increase of body weight, improvement of blood morphologic picture, regression of tumour-like changes in the liver. The case reminds the necessity of taking into account actinomycotic infection in the differential diagnosis of conditions suggesting a neoplastic process in the abdominal cavity.

Actinomycosis↗
PubMed1989

ATPase activity of the UvrA and UvrAB protein complexes of the Escherichia coli UvrABC endonuclease.

We have analyzed the ATPase activity exhibited by the UvrABC DNA repair complex. The UvrA protein is an ATPase whose lack of DNA dependence may be related to the ATP induced monomer-dimer transitions. ATP induced dimerization may be responsible for the enhanced DNA binding activity observed in the presence of ATP. Although the UvrA ATPase is not stimulated by dsDNA, such DNA can modulate the UvrA ATPase activity by decreases in Km and Vm and alterations in the Ki for ADP and ATP-gamma-S. The induction of such changes upon binding to DNA may be necessary for cooperative interactions of UvrA with UvrB that result in a DNA stimulated ATPase for the UvrAB protein complex. The UvrAB ATPase displays unique kinetic profiles that are dependent on the structure of the DNA effector. These kinetic changes correlate with changes in footprinting patterns, the stabilization of protein complexes on DNA damage and with the expression of helicase activity.

Adenosine Triphosphatases↗
PubMed1986

Mast cells in regional lymph nodes responding to syngeneic and xenogeneic tumour MSVC and HeLa cell lines in BALB/c mice.

In response to primary and secondary stimulation by xenogeneic HeLa carcinoma cells or by syngeneic sarcoma MSVC cells the regional lymph nodes of BALB/c mice are enlarged, however, their absolute mast cells content does not increase and in relative terms a decrease of mast cells concentration is observed. These results are in accordance with our earlier observations that during antigeneic and T-cell mitogen stimulation the lymphatic mast cells population does not increase but is rather reduced. This may indicate the engagement of these cells in delayed-type hypersensitivity.

Animals↗
PubMed1985

Lymphatic mast cells in response to in vitro stimulation by non-specific T-cell mitogens.

Activation of lymph nodes by the T-cell mitogens PHA and Con A is correlated with a depletion of lymphatic mast cells. This result, and our earlier reports on the depletion of mast cells in lymph nodes stimulated by allogeneic and tumour cells, as well as on the elevation of mast cell number in thymus-less 'nude' mice, lead us to the conclusion that antigen- or mitogen-stimulated T lymphocytes produce lymphokine(s) which degranulates mast cells and/or is responsible for their negative chemotaxis.

Animals↗
PubMed1985

Decrease of lymphatic mast cells in response to syngeneic WAMIB tumor cells.

In response to the syngeneic carcinoma cells the regional lymph nodes are enlarged, but their lymphatic Mast Cell content was reduced in both, relative and absolute terms. This result confirms our earlier data on the depletion of lymphatic Mast Cells in the lymph nodes stimulated by various antigens.

Animals↗
PubMed1983

Strain specific transplantable medullar carcinoma in DBA/2W mice.

A solid medullar carcinoma, which arose spontaneously in DBA/2W mouse was passed in vivo in syngeneic and semisyngeneic recipients for ten generations without alteration of its morphology. This cancer, which we named WAMIB, has a relatively slow growth ratio with MST 59 days and can be easily reproduced from cell cultures and/or from cryopreserved tumor fragments. WAMIB tumor is nearly diploid and does not metastasize, does not regress spontaneously and is rejected when grafted into allogeneic recipient animals.

Animals↗
PubMed1980

Crystallinity of human pineal calcospherulites.

Crystallinity of mineral in human pineal calcospherulites was determined by electron spin resonance spectrometry after irradiation of the samples with gamma rays in a 60Co-source. The radiation-induced stable paramagnetic centers in the crystalline lattice of hydroxyapatite crystals were used as a marker of the crystalline fraction and related to the total mineral content. The crystallinity of pineal sand is higher than that of compact bone. The numerical value of the crystallinity coefficient depends on both the average crystal size of hydroxyapatite and the percentage of the crystalline fraction in the total amount of mineral. Literature data show that the average size of hydroxyapatite crystals in pineal sand are smaller than in bone tissue. It is, therefore, concluded that the higher crystallinity of pineal acervuli is due to the lower percentage of the submicrocrystalline fraction in their mineral.

Aged↗