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P Dan

Publications and source records attributed to P Dan.

13 recordsLinked to original sources
PubMed2001

The role of hyaluronic acid in protecting surface-active phospholipids from lysis by exogenous phospholipase A(2).

BACKGROUND: This in vitro study aimed to elucidate the extent and kind of involvement of hyaluronic acid (HA) in the currently accepted view of synovial joint lubrication, in which surface-active phospholipids (SAPL) constitute the main boundary lubricant. The integrity of SAPL is apparently threatened by the lysing activity of phospholipase A(2) (PLA(2)). METHODS: The effects of increasing concentrations of HA degraded by free radicals and non-degraded HA on the lysing activity of PLA(2) were examined in vitro. Liposomes (lipid model membrane) containing phosphatidylcholine (PC) were used as the substrate, on the assumption that they are appropriate representatives of SAPL. RESULTS: HA adhered to the phospholipid membrane (liposomes), inhibiting their lysis by PLA(2). However, in its degraded form, HA not only failed to inhibit PLA(2)-lysing activity, but accelerated it. CONCLUSIONS: It is reasonable to assume that HA plays an important indirect role in the steady state of the boundary lubrication process of joints by protecting SAPL from being lysed by PLA(2). However, as excessive loading generates free radicals within the joint (among other effects), the HA that is degraded in this way is incapable of protecting SAPL from lysis by PLA(2). When the rate of degradation exceeds that of synthesis, there will be insufficient replacement of HA and/or SAPL, resulting in denudation of the articular surfaces. These are then exposed to increasing friction, and hence increased danger of degenerative joint changes.

Animals↗
PubMed2000

alpha-actinin-2 couples to cardiac Kv1.5 channels, regulating current density and channel localization in HEK cells.

Voltage-gated K(+) (Kv) channels are particularly important in the physiology of excitable cells in the heart and the brain. PSD-95 is known to cluster Shaker channels and NMDA receptors and the latter is known to couple through alpha-actinin-2 to the post-synaptic cytoskeleton [Wyszynski et al. (1997) Nature 385, 439-442], but the mechanisms by which Kv channels are linked to the actin cytoskeleton and clustered at specific sites in the heart are unknown. Here we provide evidence that Kv1.5 channels, widely expressed in the cardiovascular system, bind with alpha-actinin-2. Human Kv1.5 interacts via its N-terminus/core region and can be immunoprecipitated with alpha-actinin-2 both after in vitro translation and from HEK cells expressing both proteins. The ion channels and alpha-actinin-2 co-localize at the membrane in HEK cells, where disruption of the actin cytoskeleton and antisense constructs to alpha-actinin-2 modulate the ion and gating current density.

Actinin↗
PubMed2000

Distribution of proteins implicated in excitation-contraction coupling in rat ventricular myocytes.

We have examined the distribution of ryanodine receptors, L-type Ca(2+) channels, calsequestrin, Na(+)/Ca(2+) exchangers, and voltage-gated Na(+) channels in adult rat ventricular myocytes. Enzymatically dissociated cells were fixed and dual-labeled with specific antibodies using standard immunocytochemistry protocols. Images were deconvolved to reverse the optical distortion produced by wide-field microscopes equipped with high numerical aperture objectives. Every image showed a well-ordered array of fluorescent spots, indicating that all of the proteins examined were distributed in discrete clusters throughout the cell. Mathematical analysis of the images revealed that dyads contained only ryanodine receptors, L-type Ca(2+) channels, and calsequestrin, and excluded Na(+)/Ca(2+) exchangers and voltage-gated Na(+) channels. The Na(+)/Ca(2+) exchanger and voltage-gated Na(+) channels were distributed largely within the t-tubules, on both transverse and axial elements, but were not co-localized. The t-tubule can therefore be subdivided into at least three structural domains; one of coupling (dyads), one containing the Na(+)/Ca(2+) exchanger, and one containing voltage-gated Na(+) channels. We conclude that if either the slip mode conductance of the Na(+) channel or the reverse mode of the Na(+)/Ca(2+) exchanger are to contribute to the contractile force, the fuzzy space must extend outside of the dyad.

Animals↗
PubMed1998

Inhibition of type I and type II phospholipase A2 by phosphatidyl-ethanolamine linked to polymeric carriers.

We have previously shown that cell surface proteoglycans protect the cell membrane from the action of extracellular phospholipase A2 (PLA2) enzymes [Dan, P., Nitzan, D. W., Dagan, A., Ginsburg, I., and Yedgar, S. (1996) FEBS Lett. 383, 75-78]. Cell-impermeable PLA2 inhibitors (ExPLIs) were prepared by linking phosphatidylethanolamine (PE) to polymeric carriers, specifically, carboxymethylcellulose, heparin, or hyaluronic acid. The structure of these inhibitors enables the incorporation of their PE moiety into the membrane while the polymer remains at the membrane surface. In the present study, we show that the ExPLIs are effective inhibitors of the hydrolysis of different phospholipids in biological (Escherichia coli) and model (phospholipid vesicle) membranes, by diverse types of PLA2 enzymes, specifically human recombinant synovial fluid and C. atrox (type II), as well as Naja mocambique and porcine pancreatic (type I) PLA2. It is proposed that the external polymers of the ExPLIs, which are anchored to the membrane by the PE, mimic the naturally occurring cell surface proteoglycans and similarly protect membranes from the action of exogenous PLA2.

Animals↗
PubMed1996

H2O2 renders cells accessible to lysis by exogenous phospholipase A2: a novel mechanism for cell damage in inflammatory processes.

Phospholipase A2 (PLA2) and H2O2, secreted from activated inflammatory cells, play a central role in the tissue damage occurring in inflammatory processes. However, while exogenous PLA2 alone does not cause cell lysis, it readily does so when acting with H2O2. We have found that H2O2 degrades cell surface proteoglycans, thus rendering the membrane PL accessible to hydrolysis by exogenous PLA2. This novel mechanism introduces a role for cell surface proteoglycans in protection of cells from damage by pro-inflammatory agents, and may assign a central role for the combined action of H2O2 and PLA2 in inflammatory and bacteriocidal processes.

Animals↗
PubMed1995

Control of inflammatory processes by cell-impermeable inhibitors of phospholipase A2.

Cell-impermeable inhibitors of phospholipase A2 were prepared by linking inhibiting molecules to macromolecular carriers which prevent the inhibitor's internalization. These preparations inhibit the release of oxygen reactive species from neutrophils and cell death induced by inflammatory agents, as well as bleomycin-induced lung injury.

Animals↗
PubMed1984

Chenodeoxycholic acid pool size determination from children using isotope dilution mass spectrometry.

An isotope dilution mass spectrometry method is described for determining chenodeoxycholic acid pool size in children. The stable isotopically labeled tracer, (11,12-2H2) chenodeoxycholic acid, was administered orally to children, and the enrichment of bile was measured by selected ion monitoring gas chromatography mass spectrometry. The level of (11,12-2H2)chenodeoxycholic acid enrichment found in the patient samples was in the range of 0.5 to 5%. Data are presented illustrating the duplication of this method in two independent laboratories using standard quadrupole mass spectrometers. This procedure provides the clinician with a non-radioactive method for determining chenodeoxycholic acid pool size which is especially beneficial in studies involving children and pregnant women.

Chenodeoxycholic Acid↗
PubMed1980

Activation of adenovirus type 5 latent infections of tissue culture.

To study the in vitro activation of latent adenovirus type 5 infection and enhancement of virus production, primary human amnion and HEp-2 cell cultures were inoculated with low doses of virus and subsequently treated with steroid hormones, carcinogens, or a pyrogen drug 'Pyrago' containing killed cells of bacteria and fungi. Immunofluorescence and CPE revealed that only pyrogen induced conversion from latency to activation and that the drug also enhanced virus production. Although prednisolone failed to induce activation, it did have an enhancing effect on slowly multiplying virus. Presumably, activation and enhancement of virus replication do not occur as the result of the same mechanism but the latter may be influenced by hormones. Microbial products may produce both effects separately or simultaneously.

Adenoviruses, Human↗
PubMedDate not supplied

[Persistence of herpes simplex virus and adenoviruses in lymphocytes of patients with urogenital tumors].

Certain viruses with neoplastic potential are known to be capable of participating in tumor formation to impair the immune system. In the present study, this association was investigated in patients with urogenital tract tumors. In studies of latent virus carrier state by means of immunofluorescence techniques using specimens from 118 patients with malignant tumors and 70 control persons it was found that in more than 50% of the patients, latent antigens of herpes simplex virus or adenoviruses were present in 1-3% of circulating lymphocytes. In the control group, virus carrier state in lymphocytes was demonstrated in only few patients. Using lymphocyte blastogenesis test, the effect of nonspecific mitogen (phytohemagglutinin) induced transformation of only 10-50% lymphocytes to lymphoblast cells in patients with malignant tumors, the percentage of transformation being also dependent on the stage of the tumor process. In the control group, treatment of lymphocytes with phytohemagglutinin resulted in transformation of 55-85% of lymphocytes into lymphoblasts. The lymphocytes of the majority of patients with tumors became sensitive to specific herpes-virus and adenovirus antigens, mainly the lymphocytes of the patients whose blood cells were also virus carriers.

Adenoviruses, Human↗
PubMedDate not supplied

[Detection of the virus-specific antigens of adenoviruses and herpes simplex virus in patients with malignant genital diseases].

The possibility of detecting virus-specific antigens in women with various pathological changes of the genitalia (cancer and pre-cancer conditions) was demonstrated. Comparative examinations of specimens from patients with cancer diseases of the genitalia for the presence of structural and virus-induced early antigens of HSV-2 demonstrated immunofluorescence test (IFT) to be the diagnostic test for the detection of HSV antigens in patients with cervical carcinoma. The rate of virus-induced antigen findings in the group of patients with cervical carcinoma was 51.6%, in precancer conditions, 31.7%, in recurrent genital herpes, 78.5%, in the control group of healthy women, 5%, by the IFT. The detection of virus-specific adenovirus and herpes antigens in human tumors is of interest for further investigation of a possible role of these viruses in the generation of malignant neoplasias and for the development of methods for specific immunodiagnosis.

Adenoviruses, Human↗