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Biomedical subjects

A Grabowska

Publications and source records attributed to A Grabowska.

At least 19 recordsLinked to original sources
PubMed2006

Chemistry, photophysics, and ultrafast kinetics of two structurally related Schiff bases containing the naphthalene or quinoline ring.

The two structurally related Schiff bases, 2-hydroxynaphthylidene-(8-aminoquinoline) (HNAQ) and 2-hydroxynaphthylidene-1(')-naphthylamine (HNAN), were studied by means of steady-state and time resolved optical spectroscopies as well as time-dependent density functional theory (TDDFT) calculations. The first one, HNAQ, is stable as a keto tautomer in the ground state and in the excited state in solutions, therefore it was used as a model of a keto tautomer of HNAN which exists mainly in its enol form in the ground state at room temperature. Excited state intramolecular proton transfer in the HNAN molecule leads to a very weak (quantum yield of the order of 10(-4)) strongly Stokes-shifted fluorescence. The characteristic time of the proton transfer (about 30 fs) was estimated from femtosecond transient absorption data supported by global analysis and deconvolution techniques. Approximately 35% of excited molecules create a photochromic form whose lifetime was beyond the time window of the experiment (2 ns). The remaining ones reach the relaxed S(1) state (of a lifetime of approximately 4 ps), whose emission is present in the decay associated difference spectra. Some evidence for the back proton transfer from the ground state of the keto form with the characteristic time of approximately 13 ps was also found. The energies and orbital characteristics of main electronic transitions in both molecules calculated by TDDFT method are also discussed.

Journal Article↗
PubMed2001

Subjective contour illusion: sex-related effect of unilateral brain damage.

The aim of the study was to investigate the effect of unilateral brain lesions on the perception of subjective contours. Brain damage resulted in a reduced ability to perceive the illusion. The effect, however, was hemisphere and sex dependent. In women an illusion decrement due to either the left or right hemisphere damage was observed, while in men only right hemisphere damage caused a decrement. No specific effect of intrahemispheric localisation of lesion was found. We conclude that mechanisms contributing to subjective contour perception are right hemisphere dependent in males whereas in females they are bilaterally represented.

Adult↗
PubMed2001

Evidence for the involvement of the ventro-medial prefrontal cortex in a short-term storage of visual images.

The purpose of this study was to clarify the role of the ventro-medial prefrontal cortex in short-term visual memory. Patients with focal lesions to the right gyrus rectus were impaired on a size judgement task, which required short-term retention of laterally presented visual patterns. The impairment was most evident when the stimuli were addressed to the damaged hemisphere (left visual field presentations) and when separated by very short (50-500 ms) intervals. The findings suggest that the ventro-medial part of the orbitofrontal cortex, like the ventro-lateral part, is involved in short-term storage of icon-like representations of visual objects, and also that there exists a right-hemispheric specialization for that function. Our study presents the first direct evidence of such specific memory effects in humans using a lesion method and points to the importance of the right gyrus rectus area in maintaining the representation of stimuli after they are removed from view.

Analysis of Variance↗
PubMed2000

Antimicrobial and cytotoxic activity of hypochlorous acid: interactions with taurine and nitrite.

OBJECTIVE: HOCl, a major bactericidal product of neutrophil MPO-halide system reacts with taurine to form taurine chloramine (TauCl), a less toxic anti-inflammatory mediator. Recently, it has been reported that HOCl may also react with nitrite (NO2-), a major end-product of nitric oxide (NO) metabolism, to form very active oxidant, nitryl chloride (NO2Cl). The present study was conducted to elucidate the effect of nitrite on bactericidal and some immunoregulatory properties of HOCl and TauCl. MATERIALS: TauCl was prepared from NaOCl and taurine. The reaction was carried out at pH 5.0 and pH 7.4, in the presence or absence of nitrite. All reactions were monitored by UV absorption spectra. METHODS: Bactericidal activity of HOCl and TauCl in the presence of nitrite was tested by incubation of E. coli with the compounds and determined by the pour-plate method. To test the effect of the compounds on activity of inflammatory cells, murine peritoneal neutrophils (PMN) and macrophages were used. The cells were activated in vitro with either LPS, IFN-gamma or zymosan and the production of following mediators was measured: reactive oxygen species using luminol-dependent chemiluminescence; nitric oxide by Griess reaction; TNF-alpha using capture ELISA. In addition, we tested the effect of HOCl and TauCl on activity of myeloperoxidase (MPO). RESULTS: At physiological pH nitrite reacts with HOCl but not with TauCl. This reaction was abolished in the presence of taurine. Nitrite prevented HOCl-mediated bacterial killing, inhibition of MPO activity, cellular cytotoxicity and inhibition of TNF-alpha production. Nitrite did not affect any activity of TauCl. CONCLUSION: We have shown that nitrite may react in vitro with HOCl but not with TauCl, to form new biologically active product(s). We did not confirm the hypothesis that a product of HOCl reaction with nitrite is more toxic than HOCl. To the contrary, we found that nitrite diminished bactericidal and immunoregulatory properties of HOCl. In vivo, nitrite will also compete with taurine for reaction with PMN-released HOCl. Nevertheless, due to high concentration of taurine in PMN cytosol, formation of TauCl will be a major regulatory mechanism of MPO-halide-system.

Animals↗
PubMed2000

Differential effects of pentoxifylline, a non-specific phosphodiesterase inhibitor, on the production of IL-10, IL-12 p40 and p35 subunits by murine peritoneal macrophages.

Pentoxifylline (PTX), a methylxanthine derivative, has been reported to be an effective drug in inhibiting TNF-alpha responses during septic shock. The inhibition of TNF-alpha production seems to be correlated with increased intracellular cAMP levels. PTX also affects the production of other cytokines such as IL-1, IL-6, IL-10, IL-12, and IFN-gamma. However, inhibition, as well as enhancement of cytokine production, has been observed in vitro, depending on the PTX concentration and cell type used.IL-12 is a heterodimeric cytokine that plays an important role in the development of Th1-mediated inflammatory responses. IL-12 along with TNF-alpha and other proinflammatory cytokines has shown to be responsible for the pathological reaction, which may lead to septic shock. For biological activity, the expression of both subunits of IL-12, p35 and p40, is required. Moreover, the p40 chain of IL-12 specifically inhibits the effects of the IL-12 heterodimer. In this study, we investigated the effects of PTX on the production of both proinflammatory (TNF-alpha, IL-6, IL-12) and anti-inflammatory (IL-10) cytokines by murine macrophages (Mφ). We have found that PTX, at concentrations below 100 microg/ml, selectively inhibited the production of TNF-alpha. Forskolin, a cAMP-elevating agent, similarly affected the production of the cytokines tested. However, at higher concentrations, PTX inhibited the production of TNF-alpha, IL-10, and IL-12 p35, but surprisingly, PTX enhanced the production of IL-12 p40. Concentrations of IL-10 were negatively correlated with the concentrations of IL-12 p40 subunit. These results further confirm the relevance of the use of PTX in clinical trials of immunological disorders characterised by inappropriate Th1 type immune responses.

Animals↗
PubMed2000

The role of scintimammography with 99mTc-sestamibi as a complementary diagnostic technique in the detection of breast cancer.

PURPOSE: To prospectively determine the clinical value of scintimammography (Sc) with 99mTc-sestamibi as a complementary method to triple diagnosis (TD) in detecting malignant disease of the breast. MATERIAL AND METHODS: Ninety-six patients with 119 clinically or mammographically detected breast lesions underwent TD procedures, including clinical examination, mammography and fine-needle aspiration cytology. Prone planar Sc with 99mTc-sestamibi was performed in all 96 patients. Five groups were defined for diagnosis: 1=normal; 2=benign; 3=probably benign; 4=highly suspect of malignancy; and 5=malignant. All lesions were histopathologically examined. The results of each method per se and the combination of TD with Sc (TD+Sc) were analyzed. RESULTS: Histopathology of the 119 surgically excised breast lesions found 83 malignant and 36 benign lesions. TD missed 6 of 83 carcinomas, resulting in a sensitivity of 92.7%. Sc alone showed sensitivity of 85.5%. The combination TD+Sc missed 1 of 83 carcinomas, and thus had a sensitivity of 98.7%. In mammographically dense breasts both TD and Sc detected 16 of 18 carcinomas, while the combination TD+Sc led to detection of all 18 carcinomas. CONCLUSION: Adding Sc to TD increases the sensitivity for detection of breast carcinomas. Sc with 99mTc-sestamibi is recommended as a complimentary method to TD in selected cases such as mammographically dense breasts.

Adenocarcinoma↗
PubMed2000

Phonological and semantic fluencies are mediated by different regions of the prefrontal cortex.

Verbal phonological and semantic fluencies were investigated in 24 patients with unilateral prefrontal lesions and 10 normal control subjects. Lesions were limited to small areas within either the dorsolateral (Brodmann's area 46/9) or ventromedial (posterior part of the gyrus rectus) cortices. In a phonological fluency task, patients with lesions to the left dorsolateral region were impaired. In semantic fluency, not only the left dorsolateral group but also the two right frontal damaged groups performed worse than the control group. In agreement with previous studies, our results show that the phonological fluency is mediated by the left dorsolateral prefrontal cortex. In contrast to this, performance on the semantic fluency task depends on a wider portion of the prefrontal cortex involving the left and right dorsolateral and the right ventromedial areas.

Adult↗
PubMed1999

Taurine chloramine inhibition of cell proliferation and cytokine production by rheumatoid arthritis fibroblast-like synoviocytes.

OBJECTIVE: To examine whether taurine (Tau) or its physiologic chlorinated derivative, taurine chloramine (Tau-CI), affects proliferation of, and proinflammatory cytokine (interleukin-6 [IL-6] and IL-8) production by, fibroblast-like synoviocytes (FLS) isolated from rheumatoid arthritis (RA) patients. METHODS: FLS, isolated from the synovial tissue of 19 RA patients and cultured in vitro for 3-6 passages, were stimulated with the recombinant human cytokines IL-1beta (1 ng/ml), tumor necrosis factor alpha (TNFalpha; 10 ng/ml), or IL-17 (10 ng/ml) in the presence of either Tau or Tau-Cl, which were added at concentrations of 50-500 microM. Tau and Tau-Cl were added simultaneously with, 2 hours before, or 24 hours after the stimuli. The concentrations of IL-6 and IL-8 were determined in culture supernatants using specific enzyme-linked immunosorbent assays. Proliferation of FLS was estimated on the basis of 3H-thymidine incorporation into the cells, which were cultured for 72 hours in the presence of recombinant human basic fibroblast growth factor (bFGF) (1 ng/ml) and Tau or Tau-Cl, which were added simultaneously at the beginning of the culture. RESULTS: Cultured in vitro, RA FLS spontaneously secreted low levels of IL-6 and IL-8, but when RA FLS were stimulated with IL-1beta, TNFalpha, or IL-17, significantly higher amounts of IL-6 and IL-8 were produced. Tau-Cl, but not Tau, inhibited cytokine-triggered synthesis of IL-6 (50% inhibitory concentration [IC50] approximately 225 microM) and IL-8 (IC50 approximately 450 microM) when added simultaneously with the stimuli. However, IL-17-induced production of IL-8 was not affected by Tau-Cl. In the cells prestimulated with IL-1beta for 24 hours, Tau-Cl still inhibited synthesis of IL-6, but did not affect IL-8 production. Moreover, Tau-Cl inhibited spontaneous and bFGF-triggered proliferation of FLS in a dose-dependent manner. Neither Tau nor Tau-Cl affected cell viability. CONCLUSION: The results of these studies demonstrate that Tau-Cl inhibits production of proinflammatory cytokines by RA FLS, as well as proliferation of these cells. Thus, Tau-Cl may act as a physiologic modulator of FLS functions related to their pathogenic role in RA.

Adult↗
PubMed1999

Sex related effect of unilateral brain lesions on the perception of the Mueller-Lyer illusion.

The aim of this study was to investigate the effect of unilateral brain lesions on Mueller-Lyer (M-L) illusion in the two sexes. Patients with left hemisphere (LH) and right hemisphere (RH) damage and control subjects participated in the experiment. They inspected series of M-L patterns in which the shaft with out-going fins was gradually shortened until it induced a perception opposite to the original illusion, that is, the shaft with out-going fins appeared to be shorter than the shaft with in-going fins. The subjects' task was to decide, on each trial, whether the variable shaft was longer or shorter than the other one. The point where the judgements changed from one category to the other was established using the Spearman distribution method for determining psychophysical thresholds, and was considered the measure of the strength of the illusion. The higher the value of the threshold, the stronger the illusion. Our results showed sex-related hemispheric asymmetry in subjects' susceptibility to the M-L illusion, i.e., both LH and RH lesions in females, but only RH lesions in males resulted in an increase of the strength of illusion. Moreover, males with LH lesion as well as controls partially corrected the illusory perception with practice, while both LH and RH damaged females and RH damaged males did not show this learning effect.

Adult↗
PubMed1999

Regulation of murine dendritic cell functions in vitro by taurine chloramine, a major product of the neutrophil myeloperoxidase-halide system.

Taurine chloramine (TauCl) is a major chloramine generated in activated neutrophils as a result of the reaction of highly toxic hypochlorous acid and taurine, the most abundant free amino acid in cytosol. In this study we have tested the influence of TauCl on the properties of murine dendritic cells (DC), the major cell population involved in the initiation of an adaptive immune response against pathogenic organisms. N418+, MHC II+, B7-2+ dendritic cells, generated from the mouse bone marrow cells cultured in the presence of granulocyte-macrophage colony-stimulating factor, were stimulated by interferon-gamma and lipopolysaccharide to produce nitric oxide, reactive oxygen species, interleukin-6 (IL-6), tumour necrosis factor-alpha, and IL-12, in the presence of different doses of TauCl. TauCl differently inhibited the generation of these inflammatory mediators in a dose-dependent manner. Furthermore, TauCl selectively modulated the ability of DC to induce the release IL-2 and IL-10 from T cells. These results suggest that neutrophil-derived mediators, such as TauCl, at a site of inflammation, may affect the functions of sentinel DC and macrophages, and play a role in maintaining the balance between the inflammatory response and the induction of an antigen-specific immune response.

Animals↗
PubMed1999

Identification of type-specific domains within glycoprotein G of herpes simplex virus type 2 (HSV-2) recognized by the majority of patients infected with HSV-2, but not by those infected with HSV-1.

A combination of phage peptide display library mapping and pepscanning, with both murine monoclonal antibodies and a panel of well-characterized human sera, have been used in order to define type-specific epitopes of glycoprotein G of herpes simplex virus type 2 (HSV-2) (gG2). Both techniques revealed an immunodominant region of gG2, centred around amino acids 525-587 of the uncleaved gG2 molecule. A soluble peptide, equivalent to amino acids 551-570, when used as antigen in an ELISA format was recognized by three out of five murine MAbs and by 20/26 (77%) Western blot anti-HSV-2-positive human sera, but by only 1/63 Western blot anti-HSV-2-negative sera (specificity, 98%). The sensitivity of detection of human anti-HSV-2 antibodies was increased to 90% using a peptide derived from this region, presented on a nitrocellulose membrane. This highly antigenic and type-specific domain of gG2 is located at the junction between the 'unique' region of gG2 and its C-terminal end, which has approximately 50% identity with gG1. A second antigenic region of gG2, amino acids 351-427, which lies within the 'unique' part of gG2, was also identified by both techniques employed in this study and is recognized by a proportion of anti-HSV-2-positive sera. These findings demonstrate the feasibility of developing a peptide-based type-specific assay for the detection of anti-HSV-2 antibody in human sera based on type-specific epitopes of gG2 and have implications for the understanding of the three-dimensional topography of gG2.

Amino Acid Sequence↗
PubMed1998

Taurine chloramine down-regulates the generation of murine neutrophil inflammatory mediators.

We previously reported that taurine chloramine (TauCl), a product of activated neutrophils, inhibits the generation of macrophage inflammatory mediators such as nitric oxide (NO), TNF-alpha, and PGE2. Taurine, the most abundant free amino acid in the cytosol of neutrophils, is chlorinated to form TauCl by the halide-dependent myeloperoxidase (MPO) system. Under physiological conditions, TauCl reduces HOCl toxicity. In this study, we investigated the influence of TauCl on generation of oxygen free radicals, cytokines and eicosanoids by activated murine peritoneal neutrophils. We found that TauCl, but not taurine alone, inhibited the production of NO, prostaglandin E2, interleukin-6 and tumor necrosis factor-alpha, in a dose-dependent manner. In contrast, the products of the respiratory burst, as measured by luminol-dependent chemiluminescence (LCL), were reduced by both taurine and TauCl. However, taurine affected LCL at higher concentrations and to a lesser extent than TauCl. The results of these studies suggest that TauCl decreases production of tissue-damaging inflammatory mediators and may regulate the balance between protective, microbicidal and toxic effect of neutrophils.

Animals↗
PubMed1998

Modulation of antigen-specific T-cell activation in vitro by taurine chloramine.

Taurine chloramine (TauCl) is produced during inflammation by reaction of hypochlorous acid (HOCl) with taurine, the most abundant free amino acid in neutrophils. We previously reported that TauCl inhibits the generation of macrophage inflammatory mediators such as nitric oxide, prostaglandin E2 (PGE2), tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). In this study, the activity of TauCl in modulating T-cell activation was investigated. Treatment of T cells with TauCl (0.1-0.3 mM), prior to activation, was found to inhibit interleukin-2 (IL-2) release in response to both mitogen and antigen stimulation. Similarly, pretreatment of A-20 antigen presenting cells (APCs), at low cell numbers, was found to inhibit their ability to process and present ovalbumin (OVA) to a specific T-cell hybridoma. In contrast, pretreatment of higher numbers of A-20 cells with TauCl in the presence of OVA enhanced subsequent presentation of OVA. Finally, OVA modified with TauCl was processed and presented more efficiently than native OVA. Thus, TauCl is able to modulate induction of a specific adaptive immune response at several independent points of the overall antigen-presenting pathway.

Animals↗
PubMed1997

Enhancement of CD4+ T-cell-dependent interleukin-2 production in vitro by murine alveolar macrophages: the role of leukotriene B4.

Local tissue macrophages are known to play a key role in regulation of adaptive immune responses, often by inhibition of T-cell activation and proliferation. In this study, we compare the influence of alveolar and peritoneal macrophages on T-cell-dependent interleukin-2 (IL-2) release. Alveolar macrophages, in contrast to peritoneal macrophages, enhance IL-2 release. Assay of a panel of potential macrophage-derived mediators indicated that activated alveolar macrophages stimulated greater release of IL-1 beta, tumour necrosis factor-alpha and, especially, leukotriene B4 (> 100 times) than activated peritoneal macrophages. Inhibition of prostaglandin synthesis by alveolar macrophages further enhanced the production of IL-2, while inhibition of leukotriene synthesis abolished the enhancement. The addition of exogenous prostaglandin E2 inhibited IL-2 release, while exogenous leukotriene B4 enhanced IL-2 release. When added simultaneously, the two compounds antagonized each other's activity. In conclusion, this study confirms that alveolar macrophages enhance IL-2 secretion, and suggests that this enhancement may be due at least in part to the very high rates of production of leukotriene B4. The overall influence of macrophage populations on T cells in vivo will reflect the complex balance between the multiple mediators produced within the local tissue microenvironment.

Animals↗
PubMed1996

Is there a role for nitric oxide in regulation of T cell secretion of IL-2?

Nitric oxide (NO) can have both effector (cytotoxic) and regulatory roles in immune function. In this study, we have re-examined the potential role of nitric oxide in mediating the macrophage-dependent suppression of IL-2 synthesis. In our model, TNP-specific CD4+ T cells are cocultured with Ag and either peritoneal or alveolar macrophages. Both populations of macrophages after in vitro stimulation with IFN-gamma can inhibit IL-2 release. In vitro stimulation also induces substantial levels of NO release by these macrophages, as well as high levels of prostaglandin E2 (PGE2). However, there was no correlation between NO levels and inhibitory activity. Furthermore, NG-monomethyl-L-arginine monoacetate, a specific inhibitor of NO release had no effect on IL-2 release, while indomethacin, which blocked prostaglandin synthesis, largely abrogated the suppressor activity of both macrophage populations. Although the addition of exogenous NO donors at high concentrations could inhibit IL-2 release by T cells, our data does not support the hypothesis that NO is a major macrophage mediator of suppression in this model.

Animals↗
PubMed1996

Interhemispheric transmission of information and functional asymmetry of the human brain.

The study investigated directional differences in interhemispheric transmission time using the VEPs method. Specifically we were interested in whether there exists an asymmetry in the transmission of information to and from the hemisphere specialized in its processing. Two type of stimuli, specific for the left and right hemisphere, were presented in the left and right visual fields. The latency differences between visual evoked potential components registered in the hemispheres ipsilateral and contralateral to the stimulated hemifield were compared. Interhemispheric transmission time was shorter when the information was transferred from the hemisphere non-specialized for its processing to the specialized one than in the opposite direction. The results suggest the existence of a physiological mechanism that ensures fast transmission of information to that hemisphere which is more efficient in its processing.

Brain↗
PubMed1996

Visual-spatial-frequency model of cerebral asymmetry: a critical survey of behavioral and electrophysiological studies.

In this article, the authors present a review of research on the role of the 2 hemispheres in processing spatial frequencies. J. Sergent (1982a) postulated that the hemispheres differ in their sensitivity to frequency characteristics of the sensory outputs on which cognitive processes are performed. Specifically, she proposed that the right hemisphere displays greater efficiency than the left hemisphere in processing low-spatial-frequency content of a visual image, whereas the left hemisphere is better equipped than the right to deal with high frequencies. The authors present an extensive review of behavioral and electrophysiological studies whose researchers tried to verify Sergent's hypothesis and offer its reformulation, taking into account the findings that have accumulated in the last 10 years.

Brain↗