[Professor Anna Dubowska-Inglot].
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Cytokines↗
Biomedical subjects
E Piasecki
Publications and source records attributed to E Piasecki.
[Selenium in health and disease].
Selenium deficiency occurs in many regions of the world including Poland. It leads to human body dysfunctions and diseases among which Keshan disease is the most known. Biologically active selenium is usually incorporated into proteins as selenocysteine, which is the most useful in nutritional supplementation. Selenium addition is important since many viruses are more pathogenic when deficiency of this element occurs.
Dietary Supplements↗
Coincidence between spontaneous release of interferon and tumor necrosis factor by colostral leukocytes and the production of a colostrinine by human mammary gland after normal delivery.
We have tentatively identified colostrinines as novel cytokines produced by the mammary gland after delivery and detectable in colostrum. The primary colostrinine, the proline-rich polypeptide, was isolated from ovine colostrum in 1974. It is generally understood that the various factors present in colostrum play a pivotal role in transmitting of passive or active immunity from mother to child. We have found previously that both ovine and human colostrinines are inducers of interferon (IFN) gamma and other cytokines. In this paper, we reported that the leukocytes isolated from human colostrum donated by healthy mothers at 1-9 days after delivery, produced IFNs and tumor necrosis factors (TFNs) spontaneously. The release of IFNs and TNFs coincided with production of a colostrinine that has been isolated from the human colostrum samples and partially characterized. Our results suggest that the maximum production of colostrinine occurs 3 days after delivery. The tolerance (hyporeactivity) of the colostral leukocytes to IFN inducers and the modulation of the TNF response may be the late effects of the colostrinine release.
Breast↗
Seleno-organic compounds as immunostimulants: an approach to the structure-activity relationship.
Our studies on the seleno-organic compounds were focused at their activities as the modest cytokine inducers in human peripheral blood leukocyte cultures. Our bioassays used in the screening methods were based on the quantitative determinations of mainly two types of cytokines: interferons (IFNs) and tumor necrosis factors (TNFs). More recently we have found that several of the compounds have direct immunotropic actions in vitro and in vivo, in mice and in chickens. The paper summarizes the data related to the cytokine-inducing activity of 65 seleno-organic compounds divided into 4 groups according to their chemical structures. The reference compound was ebselen, the well known experimental drug with various biological activities. Approximately 50% of the compounds were found to be active in our bioassays. The selected compounds induced also IL-6 and GM-CSF. Their activities were clearly correlated with defined chemical structures as well as with the presence of selenium. We suggest that some of the selected by us compounds, other than ebselen, are interesting as immunostimulants and potential antiviral agents and cytokine inducers active in humans.
Adjuvants, Immunologic↗
Long-term assessment of interferon responses in the HIV+ and AIDS patients.
Impairment of interferon (IFN) system in human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) became a basis for searching IFN responses to monitor the disease progression. For detailed investigations 16 HIV+/AIDS patients with at least 4 successively taken blood samples available for IFN determinations were selected. IFN responses were tested in two ways. Firstly, IFN level in plasma was measured. Secondly, capacity of IFN production by leukocytes was evaluated. The latter was determined in the whole blood assay, in which Newcastle disease virus (NDV) and phytohemagglutinin (PHA) were used as IFN-alpha and IFN-gamma inducers, respectively. The levels of IFN induced in whole blood leukocytes varied considerably in all individuals that had been tested. Nevertheless, two patterns of IFN responses were observed. In pattern I, patients had low levels of IFN in plasma and high levels of induced IFN-alpha and IFN-gamma. It was characteristic for 8 patients in good clinical condition. On the contrary, severe disease found in 2 patients was correlated with high levels of IFN in plasma and low levels of induced IFNs (pattern II). In 6 patients IFN responses were classified as intermediate pattern I/II suggesting transition from pattern I to pattern II. A variation of pattern I was found in the case of a patient defined as long-term survivor having relatively low levels of all IFN tested. The results suggested that interferon measurements reflected clinical condition of HIV+ patients showing not only past but also current immune changes.
Acquired Immunodeficiency Syndrome↗
[Cytokines in persons infected with HIV and patients with AIDS].
The cytokine system is affected by human immunodeficiency virus. The virus stimulates or inhibits the production of various cytokines. On the other hand, many cytokines may interfere with HIV replication. Interferons (mainly alpha- and beta-type) inhibit and tumor necrosis factors stimulate the virus replication in vitro. However, in vivo in HIV-infected patients it appears that IFN but not TNF is reliable progression marker of AIDS.
Acquired Immunodeficiency Syndrome↗
Interferon responses in schizophrenia and major depressive disorders.
The spontaneous and induced interferon (IFN) production in whole blood cultures was examined in 45 psychiatric inpatients and in 65 normal controls. Among inpatients there were 32 who were chronic schizophrenics (14 women, 18 men) and 13 who were severely depressed (11 women, 2 men). The analysis of the pooled results of assays in the heterogeneous population showed that leukocytes of the psychiatric patients produced significantly lower levels of IFN after stimulation with virus (NDV), lipopolysaccharide (LPS), and IFN spontaneously released without the inducers that control cells. In contrast, there was no difference between the psychiatric patients and controls in IFN response to phytohemagglutinin and phorbol myristate acetate (PHA + PMA). The results apparently confirmed observations made by Moises et al (1985) and Katila et al (1989). We have also tested our hypothesis that the statistics may mask the individual pattern of IFN response related to the specific psychiatric diagnosis, however. In fact, in the group of chronic schizophrenics we have found either high or low responders to all IFN inducers (NDV, PHA + PMA and LPS). Furthermore, the patients with high IFN response had dominant positive symptoms of schizophrenia (delusions, hallucinations, bizarre behavior and thought disorder). Whereas, in the patients with low IFN response the negative symptoms prevailed (asociality or withdrawal, flat affect, attention impairment, abolition or apathy). In plasma samples of schizophrenics, factors were detected that transferred a hypersensitivity to the IFN inducers to normal donor leukocytes. For instance, in leukocytes cultured in the presence of plasma from schizophrenics, there were 71% of high IFN responders after stimulation with NDV, versus 26% of high IFN responders in the presence of plasma from normal controls. We suggest that the factors may belong to the class of opioid peptides, which interact with the production of cytokines including IFNs.
Adult↗
Interferon and tumor necrosis factor responses of HIV+ patients as markers for monitoring of the AIDS progression.
The blood samples taken from 31 HIV+ and AIDS patients were used to study interferon (IFN) and tumor necrosis factor (TNF) responses. The IFN and TNF levels in plasma were determined. In the whole blood assay (whole blood diluted 1:10 with culture medium) Newcastle disease virus (NDV) and phytohemagglutinin (PHA) were used as cytokine inducers. Blood leukocytes of HIV+ patients produced significantly less IFN-alpha after NDV stimulation than the cells of healthy (HIV-) individuals. On the other hand, the production of IFN-gamma in response to PHA was impaired only in AIDS patients with stage CDC IV and CD4+ cell number < 200/microliters. These patients had also increased IFN levels in plasma. Particularly, the high level of IFN in plasma was frequently detected in patients with progressing AIDS with CD4+ cell number < 50/microliters. This type of IFN was identified as a mixture of acid-labile and acid-stable IFN-alpha. The IFN responses of HIV+ patients may be considered as markers for monitoring progression of AIDS and therapy.
Acquired Immunodeficiency Syndrome↗
Tołpa Torf Preparation (TTP) induces interferon and tumor necrosis factor production in human peripheral blood leukocytes.
Tołpa Torf Preparation (TTP) is a natural immunomodulating drug registered in Poland for use in humans. TTP is a biologically active low molecular weight fraction of an extract from peat containing organic substances, primary bound sugars, amino-acids, uronic and huminic acids and mineral salts. The toxicity of TTP is remarkably low, eg. cytotoxicity (CD50) for human peripheral blood leukocytes (PBL) is 1-9 mg/ml. We have discovered that TTP is an interferon (IFN) and tumor necrosis factor (TNF) inducer in human PBL. The IFN and TNF response of the PBL cultures was dose dependent. The optimal concentration of TTP for IFN or TNF response was 10-100 micrograms/ml. The cytokines stimulated by TTP were IFN-gamma, IFN-alpha and TNF-alpha. Ten commercial batches of TTP have been found to be active as cytokines inducers although variations in their activities were observed. On the other hand, 8 batches of TTP rejected by the producer because of the inadequate immunostimulating activity determined in mice, were found to be significantly less active than the commercial preparations. Over 115 buffy coats from the individual blood donors were used to prepare PBL cultures for this study. Approximately 20% of the PBL cultures were unresponsive to TTP. The IFN and TNF response of PBL to other inducers: phytohemagglutinin (PHA) or lipopolysaccharides (LPS) also varied. Whereas only 7% of PBL could not be stimulated by PHA, as much as 20-50% of PBL failed to produce IFN or TNF when treated with LPS. We suggest that TTP may have clinically useful activities connected with the capacity of stimulation of IFNs and TNF production.
Adjuvants, Immunologic↗
[Prions].
Prions are proteinaceous infectious particles. They are probably devoid of nucleic acid. Prion protein (PrP) is encoded by the normal cellular gene. Pathological isoform of prion protein has different conformation than the normal PrP protein. The exact nature of the posttranslational modification of prion protein is unknown. This modification may be caused by infection with prions (infectious disease) or occurs spontaneously (sporadic disease). Some mutations in PrP gene results in the production of pathological protein (familial disease).
Animals↗
Seleno-organic compounds induce interferon and tumor necrosis factor in human but not in rat or mouse lymphoid cells.
The seleno-organic compounds are highly active in several anti-inflammatory assays performed in mice and rats. However, they differ from the classical non-steroidal anti-inflammatory drugs including indomethacin despite the fact that both types of drugs are inhibitors of prostaglandins and leukotrienes. Furthermore, ebselen and analogs are potent anti-oxidants in many animal cell cultures. The toxicity of the drugs is low because selenium in their structure is not bioavailable. We have discovered that the seleno-organic compounds induce interferon gamma (IFN-gamma), IFN-alpha, tumor necrosis factor alpha (TNF-alpha) and other cytokines in human peripheral blood leukocytes (PBL). Furthermore, the action of the drugs and PHA or Con A was synergistic. However, ebselen and analogs were found to be inactive as the cytokine inducers in cultured rat or mouse lymphoid cells. In contrast to their effects in human PBL, the drugs even inhibited the production of IFN-gamma after stimulation with PHA or Con A. The inhibition was dose dependent. We suggest that the induction of IFN by ebselen and analogs is species specific and it may depend on interaction of the drugs with a specific receptor and/or signal-transducing system present in human but not in some animal cells.
Animals↗
Simultaneous induction of interferon gamma and tumor necrosis factor alpha by different seleno-organic compounds in human peripheral blood leukocytes.
Ebselen is known as anti-inflammatory and anti-oxidant selenium containing drug. We have synthetized 13 seleno-organic compounds, analogs of ebselen. Seven of them were found to be inducers of interferon gamma (IFN-gamma) and/or tumor necrosis factor alpha (TNF-alpha) in human peripheral blood leukocytes (PBL) cultures. The most active cytokine inducers were: 2-phenyl-1,2-benzisoselenazol-3(2H)-one (1, ebselen), bis [2-(N-phenylcarbamoyl)]phenyl diselenide (7) and bis (2-[N-(2-pyridyl)carbamoyl])phenyl diselenide (8). The amounts of IFN and TNF produced by PBL cultures in response to the seleno-organic compounds were found to be similar to that induced by phytohemagglutinin (PHA). The activities of the seleno-organic compounds were dose-dependent and related to the chemical structure of the drugs suggesting involvement of the specific cytokine-inducer receptor. The simultaneous inductions of IFN-gamma and TNF-alpha were highly correlated, but independent on each other.
Anti-Inflammatory Agents, Non-Steroidal↗
Nuclear disassembly of the Pb+Au system at Elab=29 MeV per nucleon.
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Journal Article↗
Effects of some lipophilic carboxylic acid on release of interferon gamma from the human peripheral blood leukocytes.
Lipophilic carboxylic acids and their salts were tested for the ability of interferon induction in the cultures of human peripheral blood leukocytes. Of 13 tested organic compounds, two were selected: decyl-malonic acid and sodium salt of octylmethane-tri-(2-oxabutanoic)acid--which stimulated the synthesis of low amounts of gamma interferon.
Carboxylic Acids↗
Organoselenides as potential immunostimulants and inducers of interferon gamma and other cytokines in human peripheral blood leukocytes.
A number of organoselenium compounds have been described as anti-inflammatory, antioxidant, glutathione peroxidase-like agents and inhibitors of prostaglandin synthesis. Here we report that bis [2-(N-phenyl-carboxamido)]phenyl diselenide, 2-phenyl-1,2-benzisoselenazol-3(2H)-one (Ebselen) and related compounds are inducers of interferon gamma (IFN-gamma) and tumor necrosis factor (TNF) in human peripheral blood leukocytes. The IFN and TNF response was rapid, occurring within 20 h, and high--up to 1000 and 2000 units ml-1--and was clearly related to the dosage and the structure of the compounds. The action of the compounds and phytohemagglutinin was synergistic. The IFN gamma and TNF production was reduced after removing adherent cells. Although the mode of action of the compounds is not known, they appear to interact directly or indirectly with both adherent and non-adherent leukocytes, and stimulate the synthesis of a set of different cytokines including factors controlling the cell proliferation. Therefore, organoselenides may be regarded as the biological response modifiers.
Adjuvants, Immunologic↗
Antigen-specific and nonspecific interferon response of peripheral blood leukocytes from patients with chronic brucellosis.
Thirty seven blood samples from 21 patients with chronic brucellosis were studied for interferon response to Brucella specific antigens and to the classical IFN inducers. Whole blood technique for IFN induction and bioassay with A549 cells challenged with EMC virus for IFN detection were used. Two different antigen preparations (BRU-1 and BRU-2) used for the serologic diagnosis of brucellosis, stimulated significantly (P less than 0.001) the synthesis of IFN-alpha and IFN-gamma in the whole blood cultures from the patients with chronic brucellosis but not from the control subjects. The detoxified antigen (brucellin) was inactive as the IFN inducer. BRU-1 and BRU-2 antigens induced also low levels of IFN-alpha + IFN-gamma in the short term cultures of the separated peripheral blood leukocytes (5-10 X 10(6) cells/ml) from healthy blood donors. This resembled stimulation of the leukocytes with LPS. Brucellin was inactive in the leukocyte culture. Despite the chronic infection lasting many years the brucellosis patients had apparently intact IFN system because the response of their leukocytes to NDV, PHA + PMA or LPS was not significantly different from that of the healthy blood donors. The importance of the relative balance of the IFN system for the pathogenesis of brucellosis is suggested and contrasted with IFN disfunction in the acquired immune deficiency syndrome.
Adult↗
Isotopic composition of high-activity particles released in the Chernobyl accident.
Gamma spectra were measured and activities of the detected isotopes were analyzed for 206 high-activity particles (hot particles, HPs) found in northeastern Poland after the Chernobyl accident. The isotopic composition of HPs observed in gamma-activity is compared with that of the general fallout and core inventory calculations. Particle formation and a process of depletion in Ru and Cs isotopes are discussed. On the basis of a search performed a year later, some comments on the behavior of HPs in the soil are made.
Accidents↗
Psychological support and psychiatric management of patients with automatic implantable cardioverter defibrillators.
There are well over 6,000 automatic implantable cardioverter defibrillators (AICD) that have been implanted in the United States since 1980. The device clearly reduces arrhythmic mortality in high risk patients. Many AICD patients have other cardiac diseases, most commonly, coronary artery disease with associated prior myocardial infarctions. These patients have special psychosocial stresses that may make them vulnerable to depression and other psychological disturbances. Psychological support together with psychiatric treatment, if needed, should be provided to these patients. Use of psychotropic medications should be closely monitored, especially in this population, as many of these drugs can exacerbate ventricular tachyarrhythmias. Special precautions should also be taken when administering electroconvulsive therapy in these patients.
Adjustment Disorders↗